(No emergencies or surgery- these must go to nearest polyclinic or hospital ER). . . Holistic integrative chronic natural medicine practice (HRT, pain relief, infection eg HIV AIDS, TB, /cancer/obesity screening & prevention;
Category Archives: cancer
update 16 May 2016. to our health: email@example.com
HIGH TO MASSIVE DOSE VITAMIN D3 IMPORTANCE – TEN TIMES MORE THAN MAXIMUM SUNLIGHT CAN PROVIDE – IN REVERSING COMMON VIT D DEFICIENCY/RESISTANCE FOUND IN ALL MAJOR DISEASE eg ALL INFECTIONS, INSOMNIA, MULTIPLE SCLEROSIS MS, Myasthenia Gravis, SLE, RA, PARKINSON’S, DEPRESSION, VASCULAR DISEASE, CANCER, VITILLIGO, PSORIASIS, PERIPHERAL NEUROPATHIES, MENTAL ILLNESS.
introduction: Cape Town is the world epicenter of epidemics (of poverty – malnutrition- HIV- HAART- TB –Diabetes, asthma-COPD, and vitamin D and iodine deficiency). And we are seeing neuroarthropathy with a vengeance in our township clinics, where a majority of such diabesity or/and HIV patients admit if questioned to chronic burning cramping legs and sore muscles/joints if not also consequent insomnia, falls and leg ulcers.
Poor ill patients seem to accept it- neuroarthropathy- as a way of life since it usually has no visible signs (for anyone to see) till late– poor circulation, ulcers, falls, arthritis- , and malnourished diabesity patients have bigger worries with uncontrolled diabetes and often uncontrolled hypertension despite even insulin; and the HIV+-Tuberculosis patients have the multiple toxic burdens of antiretroviral and antituberculous therapy.
Because the burden of these diseases as well as stress from corruption and violence here is amongst the highest in a major city in the world, affecting especially the poorest and most illiterate labourers, state clinics rarely have budgets to cover the necessary vitamin and mineral supplements the poor also need on their poverty fast food diet.
Our patients accept that in return for life extension by designer antimicrobials and antidiabetic/ antihypertensives, all they will get for pain relief is the combination of physiotherapy, and designer synthetic palliative drugs- paracetamol, ibrufen /diclofenac, tramadol, amitryptiline, and if lucky some ung meth sal . These factory-synthesised drugs give little relief, and no improvement in prognosis since they do not address the proximate causes of the neuroarthropathy, associated depression and work incapacity (and later strokes, arthritis, dementia, ulcers, gangrene, chronic lung/heart/ liver/ kidney/visual disease)- respective causes including stress, infective, drug-induced, tissue glycogenation, the misguided fast-food high carbohydrate-low fat diet obesity; and manual labour/multiple trauma wear and tear, and nutritional deficiency including much-needed marine and saturated fats, vitamins and minerals..
The pioneer work discussed below in Pakistan(Salahuddin ea, Basit ea), Italy (Cipriani ea) and Brazil (Coimbra ea) in using respectively Vit D3 ~700 000iu loading dose and chronically up to 1000iu /kg/day ie average 70 000iu/day, up to 120000iu per day to reverse deadly acute and chronic disease, is comparable in its simplicity safety and low cost to :
*Semmelweis’ revolutionary discovery Vienna in the mid 19thC of hand disinfection to decimate childbirth sepsis deaths; and
*Pauling’s landmark lifesaving escalation of Vit C dose to a gm per kg per day for all severe disease; and
*the parallel discovery in UK and USA of the crucial role of not just the RDA preventative microdose but also the pharmacological anti-disease benefits of 10 to 100times bigger doses of all the vitamins B complex 1 to 12.
Cipriani ea 2010 seems to be the first report on Pubmed of deliberate oral dosing with megadose 600 000iu vit D3 ie 10 000iu/kg, albeit only in health to assess bloodlevel response and safety. Since then, as we previously noted, 2 million unit single overdose in nonagenarians in Netherlands has been shown to do no harm – ie about 40 000iu/kg. .
And as the Australians and others report below, there is no hint of vigorous vitamin or mineral supplements being stigmatized as performance enhancing for eg sport – despite vitamin D3 having the distinction of being truly an anabolic ie performance-enhancing (seco)steroid .
There is no point in giving vitamin D by injection (except in those in ICU on prolonged nil per mouth) since it is so well absorbed provided given with fat eg in fishoil/coconut/DMSO oil. And obviously the higher the dose given, the more important to avoid more than a traditional multisupplement pill a day with low calcium and vitamin A retinol; combined with a low calcium diet (ie low dairy low peanut) ; and supplementing plenty fresh green produce [providing magnesia a few hundred mgs a day, and vitamin K2 perhaps 35mcg/d].
Dr Mike Holick Prof of Medicine at Boston University interviewed by Dr Joe Mercola Dec 2015 details the rationale underpinning the (eg Coimbra) massive vit D3 dose regime for severe immune disease, “as opposed to plenty of sensible sun exposure for general good health and lower deathrate from all diseases and infections. Most melanoma occurs on the least sunexposed skin, with lower melanoma and all other deaths with high sun exposure. Dark days promote melatonin and thus daytime sleepiness and depression- which bright light in the morning for an hour reverses, and elevates b-endorphan, which has many times the painkilling effect of morphines ie opioids, and antidepressants. Vitamin D deficiency more than doubles the risk of all diseases; even 2000iu vit D3 a day in the 1st yr of life in Finland halved the risk of type 1 diabetes– with loss of protection if vit D dose dropped to 400iu/day. Vitamin D/ sunlight reverse leukemic cells. But maximum sunlight exposure nearer the tropics still only elevates 25OHvit D level to a maximum of about 50ng/ml- whereas increasing evidence proves that it may take more than 10 times that bloodlevel to prevent and treat deadly diseases- depending on your genetic vitamin D receptors.
Even 1000iu/d vit D with bld level about 30ng/ml halves risk of many cancers, with doubling benefit as 25OHvit D level is doubled serially eg by 10 000iu/d or 50 000iu/d. The kidneys however limit production of the hypercalcemic 1,25vit D, thus avoiding hypercalcemia provided calcium intake is not supplemented by calcium pills, nuts. vit A etc. The higher the vit D level above 30ng/ml (up to >? 500ng/ml), the more of our 2000 enzyme systems are activated to fight all disease without hypercalcemic risks. Hunter gatherers had levels twice as high as dressed housed people today, around 50ng/ml, with increasing anticancer and antiinfection/antiautoimmune benefit from vit D up to safe levels eg 100ng/ml and higher. .”
At Thisisms.com this is multiple sclerosis March 2016 seems to be the latest from neurologist Dr Cicero Coimbra via grassroots health. He stresses that to cure degenerative/ autoimmune disease eg MS, Parkinson’s, SLE, RA, vitiligo ie to overcome genetic Vit D resistance may require vit D titration up to 1000iu/kg/d ie up to even 40000iu/d to 200000iu/d,
And 25OHvitD blood level to 1000ng and even 4000ng / ml for a few years to produce cure, before reducing to maintenance vit D3 eg 100iu/kg/day ie ~ 50000iu/wk.
Hypercalcemia and thus calcinosis is avoided provided PTH level is maintained in the low normal range, not suppressed. Optimal support includes low calcium and high water diet and Vit B2, magnes selenium zinc phosphor supps.
The spectrum of vitamin D3 adult dose thus extends from the
traditional prevention RDA 10iu/kg/ ie~700iu/d against rickets (infants start with 1000iu/d or 25000iu ie ½ scoop/month of standardized vit D3 100iu/mg powder)
to vigorous 100iu/kg/day (ie 50 000iu scoop /wk ) for common disease prevention/treatment (toddlers 2000iu/d/ ½ scoop/fortnight));
to massive 1000iu/kg/day eg 60 000iu/dy for severe autoimmune/immunodeficiency diseases – with mandatory monitoring of levels of calcium, creatinine, 25OHvitD3 and now PTH levels;
to mega 10 000iu/kg eg 650 000iu as a loading dose for eg TB or meningitis or severe trauma—which dose may maintain 25OHvit D3 blood levels in a “sufficiency” range above ~40ng/ml for a month or two, so obviously requires appropriate maintenance dosing.
Imported vitamin D3 100cwt concentrate powder (100iu/mg) per kg from an importing pharmacist costs about R500/kg ie R0.50/100 000iu- far lower than the cost of the highrisk plant xenocalciferol vitamin D2. Thus to the State (excluding packaging and dispensing cost) , the wholesale cost of vit D3 is about R0.15 per 50 000iu per week for maintenance dose; or for 50 000iu/day R10( US $0.6)/month ie retail abt R60pm ie US$5 for megadose therapy; compared to the quoted retail US$20/month in Brazil. .
THE NEUROPATHY OF DIABETES, DRUGS/TOXINS, POST-VIRAL,TRAUMA, SPONDYLOSIS, DEMENTIA:
Young, Dancho ea Tucson, Arizona, wrote 2012, ” Charcot arthropathy is a devastating joint condition that affects persons with neuropathy. With HIV/AIDS treatments prolonging the lives of these persons, it is likely that long-term sequelae of the disease will become more evident in the near future. Patients with this disease frequently develop peripheral neuropathy. A high index of suspicion must be raised in any patient with peripheral neuropathy of any cause and a red, hot, swollen, painful foot for Charcot neuroarthropathy to give these patients proper treatment to help prevent the devastating effects of Charcot neuropathy with its potential consequences including foot ulceration and amputation. We know only too well the same applies to diabesity, as it did in the days of heavy smoking.”
In 2013 Zubair ea in India showed that diabetics with foot ulcers had vitamin D levels 1/4 of that of matched diabetics without foot ulcers; and “factors which predict the risk of developing ulcer independent of 25(OH)D status were A1c (>6.9%) [OR 4.3), neuropathy [OR 6.9; retinopathy [OR 3.3; nephropathy [OR 3.1) and smoking [OR 4.5]. It is not clear whether the suppression of delayed wound healing seen during 25(OH)D deficiency is a secondary effect or is a direct action of vitamin D on certain components of the immune system.”
Tiwari, Singh, Swain ea at Hindu Universities Uttar Pradesh,India have shown elegantly in
*2012 Tiwari ea Vascular calcification in diabetic foot and its association with calcium homeostasis. Vascular calcification (VC), long thought to result from passive degeneration, involves a complex process of biomineralization, frequently observed in diabetes and an indicator of diabetic peripheral vascular disease.. ..In 74 patients with diabetic foot ulcer, Vascular calcification was present in 42% of patients. Significant difference in vitamin D, HbA1C, and eGFR levels was observed in VC +ve compared to VC -ve. Severe vitamin D deficiency was more common in VC +ve (51%) compared to in VC -ve (18%). Sub-group analysis showed that the risk of VC was significantly higher (RR = 2.4, P < 0.05) in patients with vitamin D < 10 ng/ml compared to others. .and
* Br J Nutr. 2013. Tiwari ea Prevalence and severity of vitamin D deficiency in patients with diabetic foot infection. In Diabetic Patients with and without infection (n289), 25(OH)D (nmol/l) was significantly lower (16) v. 20ng/ml P < 0·001) in cases than in controls. Risk of severe vitamin D deficiency (25(OH)D < 10ng/ml) was significantly higher in cases than in controls (OR 4·0, P < 0·0001). Age, duration of diabetes and HbA1c were significantly higher in cases than in controls and therefore adjusted to nullify the effect of these variables, if any, on study outcome. The study concluded that vitamin D deficiency was more prevalent and severe in patients with diabetic foot infection. ; and the need for vitamin D supplementation in such patients for a better clinical outcome
*.in Br J Nutr.. 2014 Tiwari ea show Vitamin D deficiency is associated with inflammatory cytokine concentrations in patients with diabetic foot infection . Vitamin D is a potent immunomodulator and a common deficiency in different population groups including patients with diabetic foot infection. in 112 diabetic foot infection cases and 109 diabetic controls , cases had significantly higher concentrations of IL-6 (P≤ 0.001), IL-1β and TNF-α (P≤ 0.006) than controls. Risk of severe vitamin D deficiency (25(OH)D <10ng/ml) was significantly higher in cases than in controls (OR 4·0, P < 0·0001). A significant negative correlation was also observed between 25-hydroxyvitamin D concentration and circulating concentrations of IL-1β (r -0.323; P≤ 0.001) and IL-6 but not between 25-hydroxyvitamin D and TNF-α and IFN-γ concentrations.
This year 2016 Wukich , Sadoskas ea. University of Pittsburgh & Georgetown USA in Diabetes Metab Res Rev. show that (Charcot) neuroarthropathy (CN) of the ankle and hindfoot is challenging to treat surgically or nonsurgically. Deformities associated with ankle/hindfoot CN are often multiplanar, resulting in malalignment; and shortening of the limb often occurs from collapse of the distal tibia, and ankle, with significant alterations in the biomechanics of the foot. eg predisposing the patient to lateral foot ulceration. Collapse of the talus, secondary to avascular necrosis or neuropathic fracture, further accentuates these deformities and contributes to a limb-length inequality CONCLUSION: Surgical reconstruction of ankle and hindfoot CN is associated with a high rate of infectious and noninfectious complications. Preoperative measures that can improve outcomes include assessment of vascular status, optimization of glycemic control, correction of vitamin D deficiency and cessation of tobacco use.
Now 2016 Basit A, Malik RA5 ea in Universities Karachi Pakistan & Manchester UK , show that A single intramuscular dose of 600 000 IU vitamin D in 143 participants with predominantly type 2 diabetes, aged ~ 52.3years, with high Douleur Neuropathique 4 (DN4) score by 20 weeks gave significant increase in 25(OH)D (from 31.7 to 46.2±10.2 ng/mL, p<0.0001) and significant reduction (p<0.0001) in positive symptoms on the DN4 , and total pain score (p<0.0001, The Basit – Malik Pakistan-Manchester paper showing great efficacy of 600 000iu vit D3 load dose in peripheral neuropathy diabetics matches the huge 40% improvement benefit of similar loading and monthly vit D3 dose against severe PTB shown by Salahuddin ea in Pakistan in 2013 http://www.ncbi.nlm.nih.gov/pubmed/23331510 that we have previously analyzed in this column
ie apart from smoking; the very low vitamin D levels common in most but especially ill people associate with about 5 fold risks of uncontrolled diabetes, infections, retinopathy , progressive leg ulcers, peripheral neuropathy and arthritis- Charcot arthroneuropathy- -and thus gangrene and amputation; and vigorous safe (supraphysiological) vit D boost reverses the risks. .
And a reminder that a 2015 study in Cape town from Coussens ea Universities in W Cape and Penn State confirm what we see daily in practice, that vitamin D deficiency is endemic in our population
while as we have pointed out repeatedly, the State here continues to dispense the inferior vitamin D2 (as the fraudulently labeled “strong calciferol”, not disclosing that it is ergocalciferol D2) despite this plant xenohormone vit D2 having been rejected by world authorities in favour of the much cheaper and effective human D3 cholecalciferol.
And now 2016 Cadegiani , Brasilia, Brazil another landmark massive-vit D dose report ; Remission of Severe Myasthenia Gravis After Massive-Dose Vitamin D Treatment.. Vitamin D has been shown to be related to autoimmune diseases, such as multiple sclerosis and psoriasis. Correlations have been reported between vitamin D levels and prevalence and severity of other autoimmune disorders, and also between vitamin D therapy and disease improvement and remission. This reports a patient with severe and refractory myasthenia gravis (MG) who followed a massive-dose treatment (80,000 to 120,000 IU/day) promoted by a medical center in Brazil (Coimbra ea) and she had her first complete remission after this type of treatment for at least 18 months (ie at least 50 million iu) with increased vitamin D serum levels (400 to 700 ng/mL) and major fall in her AChR antibodies – but acute relapse when vit D was inadvertently stopped and her vit D level halved; with again recovery when megadose vit D was resumed CONCLUSIONS: This case may reinforce the reported correlation between vitamin D level and disease severity and introduces a possible new use for vitamin D as a potential target for treating autoimmune diseases. We recommend large, double-blind, placebo-controlled, randomized studies using high-dose vitamin D treatment for refractory autoimmune diseases to reliably assess this pharmacotherapy target for these diseases.
The above case concurs with previous reported massive dose daily vitamin D3: Finamor , Coimbra ea , Universities of Brazil 2013 A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis. Autoimmunity has been associated with vitamin D deficiency and resistance, with gene polymorphisms related to vitamin D metabolism frequently described. High doses of vitamin D3 may conceivably compensate for inherited resistance to its biological effects. Nine patients with psoriasis and 16 patients with vitiligo received vitamin D3 35,000 IU once daily for six months ie ~7million iu in association with a low-calcium diet (avoiding dairy products and calcium-enriched foods like oat, rice or soya “milk”) and hydration (minimum 2.5 L daily).. After treatment 25(OH)D3 levels significantly increased (from ~15 to 106-132ng/mL. PTH and 25(OH)D3 serum concentrations correlated inversely. The PASI score significantly improved in all nine patients with psoriasis. Fourteen of 16 patients with vitiligo had 25-75% repigmentation. Serum urea, creatinine and calcium (total and ionized) did not change and urinary calcium excretion increased within the normal range. High-dose vitamin D3 therapy may be effective and safe for vitiligo and psoriasis patients.
neurologist Prof Dr Cicero Coimbra from Univ Sao Paulo presents their results since 2002 in over 4000 pts ( 1000 patients each with multiple sclerosis and Parkinson’s diseases), who have been well controlled without other therapies, provided the dose is high enough- 10 000iu/d up to about 1000iu/kg/d eg >70 000iu/d for the obese, on a low calcium ie low dairy/peanuts diet, high fluid intake and high exercise, to normalize blood calcium, and titrate PTH level to the low normal range. Dr Cicero Coimbra discusses high dose vitamin D toxicity: https://www.youtube.com/watch?v=Vxwk-YPrx7o&feature=youtu.be. PTH level should not be completely suppressed. In their clinic ( of 7 doctors) for Autoimmune chronic diseases incl MS, RA, SLE, psoriasis, vitiligo, type 1 diabetes , they have treated over 4500 pts on this high quality vit D3 high fluid low calcium diet protocol, with only 14 cases of reversible vitamin D toxicosis (hypercalcemia) so far detected ie 0.3%. Babies of mothers thus treated in pregnancy have high psychomotor development. (Vitamin C supplement should not be concurrently excessive to avoid oxalosis). They define success as being disease-free or non-progressive old fixed disabilities- 95% reach full cure. There vit D3 therapy costs only ~US $20/mo, to optimize the immune system against both infections and autoimmune disease let alone cancer. Optimal dose of vit D3 replacement becomes at least 10 000iu/day for adults especially with autoimmune diseases due to common vitamin D resistance. Ideally testing baseline blood and urine at baseline and after a few months on at least 10 000iu/d.
In Effect of a single oral dose of 600,000 IU of cholecalciferol on serum calciotropic hormones in young subjects with vitamin D deficiency:. 2010. Cipriani ,Minisola ea .University of Rome Italy tested 48 young subjects with vitamin D deficiency with a single oral dose of 600,000 IU of cholecalciferol. The 25(OH)D level was ~15.8ng/ml at baseline and became ~77ng/ml at 3 d (P < 0.001) and ~62 ng/ml at 30 d (P < 0.001). The trends were maintained in a subgroup followed up to 90 d (P < 0.001). Mean serum Ca and P significantly increased compared to baseline, whereas serum Mg decreased at 3 d. CONCLUSIONS: A single oral dose of 600,000 IU of cholecalciferol rapidly enhances 25(OH)D and reduces PTH in young people with vitamin D deficiency.
Looking at some new alarmist myth refs about vit D3 overdose :
Moderate ie physiological increase in just vitamin D levels and intake (from average diet and sunshine and a traditional supplement) within the average population bloodlevel range understandably has modest benefit- reversing at least rickets- in an indoor living clothed population, even 1st world middleaged: from Wisconsin Univ, Karen Hansen ea’s recent RCT – JAMA 2015- Treatment of Vitamin D Insufficiency in Postmenopausal Women– confirmed this, showing little practical benefit shortterm (ie over 12mo) between placebo, and supplemented vit D3 5600iu/wk and 25000 iu a week, (~3600iu/d); the highest dose perhaps doubling the baseline 20ng/ml 25OH vit D level. ie into the low “adequate” range average around 40ng/ml.
Be aware again that the same university’s group published in 2014 An Evaluation of High-Dose Vitamin D 2 for Rheumatoid Arthritis Karen Hansen ea that vit D2 ~100 00iu/month for a year actually worsens patients and lowers vit D3 levels , so there is no longer excuse for using vitamin D2 supplement when it blocks D3 receptors and lowers blood vit D3.
The inferiority of vit D2 was confirmed in eg Clinical Trial of Vitamin D2 vs D3 Supplementation in Critically Ill Pediatric Burn Patients. Gottschlich, Kagan U Cincinnati Ohio 2015: 50 patients aged 1 to 18yrs with burns were enrolled. All participants received multivitamin supplementation , plus , 100 IU/kg D2, D3, or placebo daily RESULTS: There were no significant differences in serum vitamin D levels between groups, but >10% of patients had low 25OHD at discharge, and %deficiency worsened by the 1-year follow up for the placebo (75%), D2 (56%), and D3 (25%) groups. There were no statistical differences in clinical outcomes between treatment groups, although vitamin D supplementation demonstrated clinically relevant decreases in exogenous insulin requirements, sepsis, and scar formation. The high incidence of low serum 25OHvit D levels 1 year following serious thermal injury indicates prolonged compromise. Continued treatment with vitamin D3 beyond the acute phase postburn is recommended to counteract the trajectory of abnormal serum levels and associated morbidity.
The perception seems to be that up to 40 000iu vit D3 a day, a bld level below abt 150-350ng/ml is safe, ie unsafe above that. The evidence for such ceiling ie higher dose harm in fact is lacking since as we have previously discussed here, healthy people have taken up to 150 000iu a day for decades without evidence of harm… provided they took adequate fluids, and did not take supplements of calcium, or also take high vitamin A which notoriously causes acute hypercalcemic toxicity, or have rising calcium levels . .
But note that vit K2 improves absorption of vit D3 CHOLECALCIFEROL , and vit K2 and magnesia improve benefit of vit D3,while protecting against overdose effects ie calcification, stones and confusion. Problem in many toxicity reports is that they used either vit D2 ergocalcif (WHICH BLOCKS THE NEEDED D3) , or used accidental massive overdose (millions of units vit D ) daily for months- or massive INJECTIONS) or combined vit D WITH CALCIUM REPLACEMENT AND/ OR EXCESSIVE VITAMIN A – which combinations are dangerous; we need magnesium (not calcium or high vitamin A supplements).
Vitamin D3: What’s the Latest? recent 2015 reviews from Univ California and CommonHealth contrast the Instit Medicine IOM (Big-Pharma-sponsored) conservative target of vit D3 800 to max 4000iu/d with much evidence that safe optimal D3 dose may be up to 10 000 to 50 000iu/d, and up to 1 000 000iu as an acute eg antiinfection loading dose; with risk of toxicity only if blood level exceeds 150-500ng/ml. the evidence-based IOM recommendation of optimal blood level 20-40ng/ml, up to 2000iu a day promoted by conservatives like Prof JoAnn Manson, contrasts with the more proactive view of eg Prof Michael Hollick and the Vitamin D Council promoting double that dose as supplements, safely up to 10 000iu/day.
SO I continue to take vit D3 ~70 000iu/wk ie ~10 000iu/d, with vit K2 supp ~700mcg a wk ie 100mcg/dy and a balanced multisupplement incl. magnesia in addition to a multisupplement A-Z, and fish oil and Lugols iodine 15% 2 drops a day; with if I do get a “flu” attack during bad weather, prompt abolition by a few antibiotic doses of topup Lugols iodine 15% a few tsp (ie ~1000mgs iodine), and vitamin D3 eg 300 000iu, and vitamin C a few tsp orally and by sniffing. .
The problem with many adverse effect reports of vit D3 overdose eg the Dominican Republic Soladek 2011 report Lowe ea below, and Prof Heaney’s response, is that they failed to even consider the massive associated overdose of the far more hypercalcemic vitamin A let alone calcium supp reported by most patients. It becomes apparent that NO calcium supplement should be encouraged on a prudent diet; but instead supplements of Vit D3, magnesia, vits K2 and C, CoQ10, and fish oil ; in addition to a balanced (A to Z) RDA-based multisupplement for seniors like eg Solal’s, Vital’s Multitime, Centrum etc.. with a low calcium diet if massive dose vitamin D3 is indicated as in autoimmune diseases (Coimbra ea).
APPENDIX: RECENT REFS:
VITAMIN D ANABOLIC STEROID ABUSE IN SPORT?
the Australian Govt Supplement Overview has an intriguing report on vit D in sports, with no hint of vit D supplement being a steroid abuse. .http://www.ausport.gov.au/data/assets/pdf_file/0003/594174/CORP_33413_SSF_Vitamin_D_FS.pdf Vitamin D is classified as a fat soluble vitamin which acts functionally as a steroid hormones. There are 2 different isoforms of Vitamin D: D3 (cholecalciferol) which is the important isomer formed in human skin and D2 (ergocalciferol) which is the plant-derived ie xeno-equivalent. D2 was the first isoform to be characterised and was first used in Vitamin D supplements and for food fortification. D3 is now considered preferable. D3 is biologically inert until converted in the liver to 25(OH)D and to 1,25(OH)D in the kidney. Vitamin D plays an important role in calcium and phosphorous homeostasis (bone health),but more so in gene expression and cell growth. The recent recognition of Vitamin D receptors in most body tissues indicates a role for Vitamin D in many aspects of health and function. Vitamin D is now known to be important for optimal muscle function.
The principal source of circulating vitamin D comes from exposure to ultraviolet B (UVB) radiation from sunlight. In 2010, the Institute of Medicine issued new Dietary Reference Intakes for Vitamin D, assuming no sunlight exposure: this included a Recommended Dietary Intake of 600 IU/d and an Upper Level intake of 4000 IU/d (www.iom.edu/vitamind). BUT no evidence has ever been published to support this ceiling intake.
Whereas Vitamin D deficiency can lead to several health issues including increased risk of bone injuries, chronic musculoskeletal pain and viral respiratory tract infections. There is also emerging evidence that supplementing Vitamin D in athletes with sub-optimal Vitamin D levels may have beneficial effects on athletic performance in particular strength, power, reaction time and balance.
There is no universally accepted definition of vitamin D deficiency however, the following definitions based on serum levels of 25(OH) Vitamin D are often cited:
Vitamin D deficiency: serum levels < 20 ng/ml (50 nmol/L); Vit D insufficiency: serum levels < 30 ng/ml
Vit D sufficiency: serum levels > 30 ng/ml Ideal Vit D range*: 30-50ng/ml
Toxicity: > 150ng/ml, when combined with raised serum calcium
(*Higher status may be preferred for athletes to allow a greater safety margin and to optimize performance; some agencies working with elite athletes often set their own thresholds for desired Vitamin D concentrations)
Ie they quote no evidence for the 25OH vit D ceiling of 50ng/ml.
Owens DJ1, Close GL ea . UK Universities . 2015..A systems-based investigation into vitamin D and skeletal muscle repair, regeneration, and hypertrophy. Skeletal muscle is a direct target for vitamin D. Observational studies suggest that low 25[OH]D correlates with functional recovery of skeletal muscle following eccentric contractions in humans and crush injury in rats. However, a definitive association is yet to be established. To address this gap in knowledge in relation to damage repair, a randomised, placebo-controlled trial was performed in 20 males with insufficient concentrations of serum 25(OH)D (~18ng/ml). Prior to and following 6 wk of supplemental vitamin D3 (4,000 IU/day) or placebo (50 mg of cellulose), participants performed 20 × 10 damaging eccentric contractions of the knee extensors. Supplemental vitamin D3 increased serum 25(OH)D and improved recovery of peak torque at 48 h and 7 days postexercise. Together, these preliminary data are the first to characterize a role for vitamin D in human skeletal muscle regeneration and suggest that maintaining serum 25(OH)D may be beneficial for enhancing reparative processes and potentially for facilitating subsequent hypertrophy.
2016 Is there an optimal vitamin D status for immunity in athletes and military personnel? He CS1, Gleeson M ea .Vitamin D is mainly obtained through sunlight ultraviolet-B (UVB) exposure of the skin, with a small amount typically coming from the diet.It is now clear that vitamin D has important roles beyond its well-known effects on calcium and bone homeostasis. Immune cells express the vitamin D receptor, including antigen presenting cells, T cells and B cells, and these cells are all capable of synthesizing the biologically active vitamin D metabolite, 1, 25 hydroxy vitamin D.There has been growing interest in the benefits of supplementing vitamin D as studies report vitamin D insufficiency (circulating 25(OH)D < 50 nmol/L) in more than half of all athletes and military personnel tested during the winter, when skin sunlight UVB is negligible. The overwhelming evidence supports avoiding vitamin D deficiency (25(OH)D< 30 nmol/L)to maintain immunity and prevent upper respiratory illness (URI) in athletes and military personnel.Recent evidence supports an optimal circulating 25(OH)D of 75 nmol/L to prevent URI and enhance innate immunity and mucosal immunity and bring about anti-inflammatory actions through the induction of regulatory T cells and the inhibition of pro-inflammatory cytokine production. We provide practical recommendations for how vitamin D sufficiency can be achieved in most individuals by safe sunlight exposure in the summer and daily 1, 000 IU vitamin D3 supplementation in the winter.
Sarris J1, Ng CH1. Ea, Universities of Melbourne, & Deakin, Australia; & Harvard Boston; 2016 show in Adjunctive Nutraceuticals for Depression: A Systematic Review and Meta-Analyses. http://www.ncbi.nlm.nih.gov/pubmed/27113121 Adjunctive standardized pharmaceutical-grade nutrients, known as nutraceuticals, has the potential to modulate several neurochemical pathways implicated in depression. A systematic search up to 2015 for clinical trials using adjunctive nutrients for depression RESULTS: Primarily positive results were found for studies testing S-adenosylmethionine (SAMe), methylfolate, omega-3 (primarily EPA or ethyl-EPA), and vitamin D,. Mixed results were found for zinc, folic acid, vitamin C, and tryptophan. . No major adverse effects were noted in the studies adjunctive omega-3 versus placebo revealed a significant and moderate to strong effect in favor of omega-3. CONCLUSIONS: Current evidence supports adjunctive use of SAMe, methylfolate, omega-3, and vitamin D with antidepressants to reduce depressive symptoms.
Raina AH1, Bhat FA1 ea ., India.. 2016 Association of Low Levels of Vitamin D with Chronic Stable Angina: A Prospective Case-Control Study. http://www.ncbi.nlm.nih.gov/pubmed/27114971 Coronary artery disease (CAD) is a major cause of death and disability in developed countries. Chronic stable angina is the initial manifestation of CAD in approximately 50% of the patients. Recent evidence suggests that vitamin D is crucial for cardiovascular health. The prevalence of vitamin D deficiency in our region is 83%. METHODS: a prospective case-control study in 100 cases of chronic stable angina compared controls. Vitamin D deficiency was defined as <20 ng/mL, vitamin D insufficiency as 20-30 ng/mL and normal vitamin D level as 31-150 ng/mL.RESULTS: The prevalence of vitamin D deficiency among cases and controls was 75% and 10%, respectively. 13% had normal vitamin D levels (31-150 ng/mL). None had a toxic level of vitamin D. Among the controls, 10% were vitamin D-deficient, 57% had normal vitamin D levels. The mean vitamin level among cases and controls was 15.53 ng/mL and 40.95 ng/mL, respectively, statistically significant (P ≤ 0.0001). Among the cases, we found that an increasing age was inversely related to vitamin D levels (P = 0.027). Low levels may be an independent, potentially modifiable cardiovascular risk factor.
Jetty , Glueck Kumar ea . Jewish Hospital Cincinnati, Ohio, USA 2016 show 12mo Safety of 50,000-100,000 Units of Vitamin D3/Week in Hypercholesterolemic Vitamin D-Deficient, Patients with Reversible Statin Intolerance. : http://www.ncbi.nlm.nih.gov/pubmed/27114973 Such Vitamin D3 therapy (was safe and effective when given for 12 months to reverse statin intolerance in patients with vitamin D deficiency. Serum vitamin D rarely exceeded 100 ng/mL, never reached toxic levels, and there were no significant change in serum calcium or eGFR
https://riordanclinic.org/2013/10/vitamins-d3-and-k2-the-dynamic-duo/ As we explore the healing power of higher doses of vitamin D3 at the Riordan Clinic, we have found it prudent to partner the safety and effectiveness of this dynamic duo. For every 5,000–10,000 units of D3 being recommended and tested for, we are recommending 100 mcg of K2 mk7 to be sure and prevent the inappropriate calcification that higher doses of D3 alone could cause.
Newsletter: Gary Null and vitamin D toxicity 2010 by John Cannell, MD http://www.vitamindcouncil.org/newsletter/newsletter-gary-null-and-vitamin-d-toxicity/ “Warning: If you intend to take massive doses of vitamin D based on this newsletter, which I highly recommend you do not, read the entire newsletter. In addition, accurate determination of side effects of massive doses of vitamin D was not available in the early 1930s, nor was accurate determination of the true amount in each pill possible. Is 2,000,000 IU/day of vitamin D toxic? Ask Gary Null, alternative medicine guru and entrepreneur. He took his own supplement, Ultimate Power Meal, for a month and became extremely ill; one batch of Power Meal apparently contained 1,000 times more vitamin D than it should. That is, it contained 2,000,000 IU of vitamin D3 per serving instead of 2,000 IU per serving. Mr. Null became sicker and sicker as he gulped it down.
After suing his own supplier for permanent physical damage, Mr. Null then reported it took 3 months to get the extra vitamin D out of his system and that he is now alive and well. If Mr. Null took it for the full month that he claims, and if his Power Meal contained 2,000,000 IU per dose, Mr. Null consumed 60,000,000 IU in one month. Could he really be fine now with no lasting injuries? In an attempt to answer that question, I went back to the 1930s and 40s. Massive doses in the 1930s The earliest references I could find to enormous doses of vitamin D were in the 1930s. In 1935, Drs. Dreyer and Reed, of the University of Illinois School of Medicine, published their observations on 700 patients treated with “massive” doses of vitamin D for up to two years.1 ….” read on..http://www.vitamindcouncil.org/newsletter/newsletter-gary-null-and-vitamin-d-toxicity/ http://www.livescience.com/50765-vitamin-d-supplements-toxicity.html
Vitamin D Overdose Dr. Liji Thomas, MD 2016 http://www.news-medical.net/health/Vitamin-D-Overdose.aspx vitamin D toxicity can occur from high intakes of supplements containing vitamin D, but not from dietary intake. Prolonged sun exposure also does not result in vitamin D toxicity because the previtamin D3 is degraded as the skin heats up, and also because of the formation of various other non-functional forms of vitamin D from the thermally activated compound. Long term intakes of vitamin D above the upper limit recommended causes symptoms of toxicity. However, the intakes must be higher than about 40,000 IU/day, or the serum level of 25-hydroxy above 500-600 ng/mL, and the patient is usually also taking excessive amounts of calcium as well.
Dietary Supplement–Induced Vitamin D Intoxication Klontz KC, Acheson DW. To the Editor 2004: Vitamin D intoxication that is associated with the consumption of dietary supplements is reported rarely. In 2004, the Food and Drug Administration (FDA) learned of the following case. A 58-year-old woman with diabetes mellitus and rheumatoid arthritis began taking a dietary supplement called Solutions IE Ageless Formula II on January 12, 2004. Fatigue, constipation, back pain, forgetfulness, nausea, and vomiting soon developed. On March 15, 2004, she was hospitalized because her speech was slurred, and a blood glucose reading taken at home was 30 mg per deciliter. On admission, her serum levels were as follows: calcium, more than 3.75 mmol per liter; 25-hydroxyvitamin D, 460ng/ml (normal range, 9-5);; parathyroid hormone, 12 ng per liter (normal range, 10 to 65); and creatinine, 265 μmol per liter. The patient was treated with intravenous normal saline, furosemide, and pamidronate. On March 19, 2004, while still hospitalized, she was informed by the product distributor of an error in product formulation such that 188,640 IU of vitamin D3/d had been added to the daily serving size of six capsules instead of the intended 400 IU. IE SHE HAD TAKEN ~12.2MILLION IU OF VIT D3 IN 2 MONTHS. At discharge on March 24, the patient’s serum levels were as follows: calcium, 2.60 mmol per liter; blood urea nitrogen, 10.0 mmol per liter; and creatinine, 221 μmol per liter. The patient died from a cause unknown to us on January 8, 2005. Laboratory analysis of the product by the FDA, obtained from one of two lots reportedly overfortified with vitamin D3, revealed 186,906 IU of vitamin D3 in each serving size of six capsules, indicating that the patient had consumed roughly 90 times the recommended safe upper limit of 2000 IU per day. Long-term daily vitamin D consumption of more than 40,000 IU (1000 μg) is needed to cause hypercalcemia in healthy persons.2 In March 2004, the product distributor announced that during the previous month it had received three complaints from customers who had been hospitalized for hypercalcemia and vitamin D toxicity
2011 Vitamin D toxicity due to a commonly available “over the counter” remedy from the Dominican Republic. Lowe H1, Bilezikian JP. ea Columbia Univ, NY.. http://press.endocrine.org/doi/10.1210/jc.2010-1999?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed& Hypercalcemia in ambulatory patients is occasionally caused by vitamin D toxicity. We report nine patients presenting to Columbia University Medical Center with hypercalcemia due to a supplement from the Dominican Republic containing massive amounts of vitamin D. All reported recently taking Soladek readily available in the Dominican Republic and in Upper Manhattan. serum calcium values before the ingestion of Soladek were not elevated According to the manufacturer’s label, each 5-ml vial of Soladek contains vitamin D3 (600,000 IU), vitamin A (120,000 IU), and vitamin E (5 mg). Laboratory analysis by HPLC revealed that the supplement actually contained vitamin D(3) (864,000 IU) and vitamin A (predominantly retinyl palmitate 123,500 IU) per vial.IE 864000 IU VIT D /day FOR UNKNOWN DURATION. a similar case was reported earlier http://www.thecamreport.com/2009/11/soladek-toxicity-in-a-60-year-old-woman/
Comments by Prof Robert P. Heany Creighton University, Omaha, Nebraska on Lowe et al: Hypercalcemia in vitamin D intoxication JCEM http://press.endocrine.org/e-letters/10.1210/jc.2010-1999 The report by Lowe et al. on vitamin D intoxication from an OTC supplement (1) is instructive and useful. I comment on the authors’ suggested mechanism of hypercalcemia in such cases. The authors propose that the elevated concentration of serum 25- hydroxy-vitamin D [25(OH)D] is the responsible agent, through loose binding to the vitamin D receptor. While my colleagues and I have shown that 25(OH)D can improve calcium absorption (2), I believe there is a simpler explanation for hypercalcemia in vitamin D intoxication, particularly as the reported values of 25(OH)D were not uniformly high in these nine cases. [In fact the patient with the highest serum calcium had actually the lowest value for 25(OH)D.] Instead, as Vieth suggested several years ago in a paper actually referenced by Lowe et al. (3), elevation of free circulating 1,25(OH)2D (calcitriol) is the most parsimonious explanation. This level is not commonly measured, and was not reported in the cases described by Lowe et al. Vieth has estimated the binding capacity of the D-binding protein (DBP) at approximately 4700 nmol/liter, and it is generally recognized that fewer than 5% of its binding sites are occupied at typical cholecalciferol inputs. However, in the face of huge cholecalciferol doses, as in the nine cases described here, it can easily be calculated that most or all of the binding sites on the DBP would be occupied by cholecalciferol itself as well as by 25(OH)D and 24,25(OH)2D, all of which are bound to the DBP more avidly than is calcitriol. Lowe et al. did not measure serum cholecalciferol, but it is virtually certain that its concentration would have been elevated, if for no other reason than that the capacity of the hepatic 25-hydroxylase is limited, and serum cholecalciferol concentration rises steeply for cholecalciferol inputs in excess of the saturation level of the 25-hydroxylase [which typically occurs at serum cholecalciferol levels of about 10 nmol/L and serum 25(OH)D of about 80 nmol/liter (4)].Even if all of the binding sites of the DBP were not continuously occupied by less polar metabolites, high occupancy would shift the equilibrium between the free and the bound calcitriol, so that free calcitriol concentration would likely have been substantially above normal values continuously. The authors speculate as to the origin of the elevated total calcitriol concentrations, given the down-regulation of the renal 1-Ã¡- hydroxylase in such cases.
2016.Deficient serum 25-hydroxyvitamin D is associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-3) study. Lupton JR1Michos ea . Cross-sectional studies have found an association between deficiencies in serum vitamin D, as measured by 25-hydroxyvitamin D (25[OH]D), and an atherogenic lipid profile. These studies have focused on a limited panel of lipid values including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG).OBJECTIVE: Our study examines the relationship between serum 25(OH)D and an extended lipid panel (Vertical Auto Profile) while controlling for age, gender, glycemic status, and kidney function.METHODS: We used the Very Large Database of Lipids, which includes US adults clinically referred for analysis of their lipid profile from 2009 to 2011. Our study focused on 20,360 subjects who had data for lipids, 25(OH)D, age, gender, hemoglobin A1c, insulin, creatinine, and blood urea nitrogen. Subjects were split into groups based on serum 25(OH)D: deficient (<20 ng/mL), intermediate (≥20-30 ng/mL), and optimal (≥30 ng/mL). The deficient group was compared to the optimal group using multivariable linear regression.RESULTS: In multivariable-adjusted linear regression, deficient serum 25(OH)D was associated with significantly lower serum HDL-C (-5.1%) and higher total cholesterol (+9.4%), non-HDL-C (+15.4%), directly measured LDL-C (+13.5%), intermediate-density lipoprotein cholesterol (+23.7%), very low-density lipoprotein cholesterol (+19.0%), remnant lipoprotein cholesterol (+18.4%), and TG (+26.4%) when compared with the optimal group.CONCLUSION: Deficient serum 25(OH)D is associated with significantly lower HDL-C and higher directly measured LDL-C, intermediate-density lipoprotein cholesterol, very low-density lipoproteins cholesterol, remnant lipoprotein cholesterol, and TG
- Low-Level VitaminD Is strongly Associated with Atrial Fibrillation in Patients with Chronic Heart Failure.Belen E1, , Cetin M2ea. Atrial fibrillation (AF) freuently accompanies heart failure (HF), and causes exacerbation of symptoms and treatment failure in such patients. Vitamin D was recently suggested to be an important mediator of cardiovascular disease, including HF.OBJECTIVES: The aim of this study was to evaluate the relationship between vitamin D deficiency and AF in patients with chronic HF. METHODS: The study included 180 chronic HF patients that were divided into 2 groups based on having sinus rhythm [AF (-) group] or chronic AF [AF (+) group]. Vitamin D status was assessed via measurement of the serum 25-hydroxyvitamin D (25[OH]D) concentration.RESULTS: Mean age of the patients was 66 ± 8.7 years and 53.9% were male. There weren’t any significant differences in age, gender, body mass index, etiology or chronic HF stage between the 2 groups. The vitamin D level in the AF (+) group was significantly lower than in the AF (-) group (11.05 ng/mL vs. 20 ng/mL, p < 0.001) The left atrium to body surface area ratio (LA/BSA) was significantly higher in the AF (+) group (45.03 mm/m2 vs. 42.05 mm/m2, p < 0.01). Independent predictors (based on multiple regression) of AF were vitamin D level (OR = 0.854, 95% CI: 0.805-0.907, p < 0.001) and LA/BSA ratio (OR = 1.077, 95% CI: 1.003-1.156, p < 0.05). The optimal vitamin D cut-off value for the prediction of AF was 16.50 ng/mL, with a sensitivity of 76.0% and specificity of 65.5% (AUC = 0.75, 95% CI: 0.67-0.82).
Vitam Horm. 2016;100:255-71. doi: 10.1016/bs.vh.2015.10.001. Epub 2015 Nov 30. Molecular Approaches for Optimizing Vitamin D Supplementation. Carlberg C1.Vitamin D can be synthesized endogenously within UV-B exposed human skin. However, avoidance of sufficient sun exposure via predominant indoor activities, textile coverage, dark skin at higher latitude, and seasonal variations makes the intake of vitamin D fortified food or direct vitamin D supplementation necessary. Vitamin D has via its biologically most active metabolite 1α,25-dihydroxyvitamin D and the transcription factor vitamin D receptor a direct effect on the epigenome and transcriptome of many human tissues and cell types. Different interpretation of results from observational studies with vitamin D led to some dispute in the field on the desired optimal vitamin D level and the recommended daily supplementation. This chapter will provide background on the epigenome- and transcriptome-wide functions of vitamin D and will outline how this insight may be used for determining of the optimal vitamin D status of human individuals. These reflections will lead to the concept of a personal vitamin D index that may be a better guideline for an optimized vitamin D supplementation than population-based recommendations.
- Comparative efficacy of vitamin D status in reducing the risk of bladder cancer: A systematic review and network meta-analysis.Zhao, , Huang J3. The optimal concentration of individual vitamin D intake for preventing bladder cancer has not, to our knowledge, been defined. To evaluate the comparative efficacy of different serum 25-hydroxyvitamin D concentrations in preventing bladder cancer, we conducted a systematic search of the literature published up to April 2015.METHODS: We applied a pairwise meta-analysis to estimate direct evidence from intervention-control studies and a network meta-analysis within a Bayesian framework to combine direct and indirect evidence. Moreover, a dose-response curve was utilized to predict the optimal median serum 25-hydroxyvitamin D concentration based on the odds ratio (OR) for each quintile concentration.: Seven studies of a total of 90757 participants, including 2509 bladder cancer patients, were included. Two prospective cohort studies with 57 591 participants and 494 bladder cancer patients, and five case-control studies with 33 166 participants and 2264 bladder cancer patients. From the network meta-analysis, we observed that sufficient serum 25-hydroxyvitamin D concentrations (>75 nmol/L) were superior to all other 25-hydroxyvitamin D concentrations in decreasing the risk of bladder cancer: OR = 0.68 and 95% credible interval (CrI) 0.52 to 0.87 compared with severely deficient concentrations (<25 nmol/L); OR = 0.65 and 95% CrI 0.49 to 0.86 compared with moderately deficient concentrations (25-37.5 nmol/L); OR = 0.61 and 95% CrI 0.47 to 0.80 compared with slightly deficient concentrations (37.5-50 nmol/L); and OR = 0.65 and 95% CrI 0.48 to 0.85 compared with insufficient concentrations (50-75 nmol/L). In addition, we noted a roughly inverse correlation between bladder cancer risk and 25-hydroxyvitamin D concentrations (R(2) = 0.98, P = 0.007).CONCLUSIONS: Ensuring sufficient serum 25-hydroxyvitamin D concentrations might play an important role in decreasing the risk of bladder cancer. The serum 25-hydroxyvitamin D concentration ≥30ng/ml was associated with a 60% lower risk of bladder cancer incidence.
the Ides of March 2016: Where have we been the past 5 years in ignoring the crucial role of K2 supplement with vit D3? against cancer, fractures, infections, vascular disease and diabetes ,
like the crucial role of Lugols iodine + selenium, and magnesium (not calcium), coQ10, and animal, marine and coconut ie saturated fat oil- supplement for all chronic disease prevention?
Considering that our western processed food staple diet, and the diet of the poor majority everywhere, is increasingly deficient especially in these nutrients, with by profit-motivated industrial design disease-promoting cholesterol-depletion, refined sugars, transfats, antibiotics, hormones, and noxious at-any-dose elements from fluorine and aluminium upwards.…
I see I was promoting K2 in my emails 4 years ago, and since 2009, on my Healthspanlife blog ie in my lectures and thus in my healthspanlife blends .
But I indeed don’t seem to have published a review of K2 on my blog- till now!
– and there are so many refs out there since the first K2 mention on Pubmed in 1946,
and its first Pubmed human supplement mention in 2002 Improvement with maternal supplement of vitamin K2 of vitamin K status of breastfeeding infants (MK40). Nishiguchi T, Terao T ea. Semin Thromb Hemost. 2002 : 28533-8.
Unlike the Big Pharma-Disease-Industry- controlled denialists of conservative safe natural phamacological vitamin therapy like the Linus Pauling Institute and Wikipedia https://en.wikipedia.org/wiki/Vitamin_K2,
the vitamin K2 Polish scientist Dr Katarzyna Maresz PhD 2015 writes (see abstract below) Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health. Maresz K1. International Science and Health Foundation Krakow, Poland Inadequate calcium intake can lead to decreased bone mineral density, thus increase the risk of bone fractures. Recent scientific evidence, however, suggests that elevated consumption of calcium supplements may raise the risk for heart disease and can be connected with accelerated deposit of calcium in blood-vessel walls and soft tissues. In contrast, vitamin K2 is associated with the inhibition of arterial calcification and arterial stiffening. Dosing of K2 was supported by a population-based study with 16 000 healthy women aged 49 to 70 years drawn from EPIC’s cohort population. After 8 years ,it showed that a high intake of natural vitamin K2 (ie, not synthetic K2, but not of vitamin K1) was associated with protection against cardiovascular events. For every 10 mcg of dietary vitamin K2 consumed (in the forms of menaquinone 7 (MK-7), menaquinone 8 (MK-8), and menaquinone 9 (MK-9), the risk of coronary heart disease was reduced by 9%. … The researchers found that a daily dose of 180 mcg was enough to improve bone mineral density, bone strength, and cardiovascular health. They also showed that achieving a clinically relevant improvement required at least 2 years of supplementation.
While vit D3 cholecalciferol soltriol was the multiprevention megavitamin of the past decade, and CoQ10 the decade before that, catching up with the protean benefits of increasingly diet- deficient vitamins published (350 000 Pubmed citations) the past century, and of vitamin K since 1936, and K2 since 1946,
vit K2 is the most publicized ie advancing megavit of the current decade:
Adequate intake ie ~45 to ~150mcg/d is crucial with magnesium, boron etc to balance vigorous vit D3 supplement,
for both bone, immune/cancer, and cardiovascular health.
Thus even just ~55mcg/d K2 supplement HALVES the risk of cardiovascular disease – very important in overweight/stressed/ aging people.
BUT The authorities quoted have assessed safety and optimal longterm effective doses of vitamin K3 and vitamin D3 IN ISOLATION for major prevention. However, we know that optimal nutrition is balanced nutrition, not one or two nutrient is superdose with an average fastfood mediocre diet.
This finally convinces me to add vit K2 ~ 35 to 100mcg/day ie 200 to 700mcg/wk to my own vit D3 supplements. at a trivial bulk wholesale cost of ~10mg/d 1% K2 ie ~R0.1/day or R14 – ( US$1) bag per 40 weeks of vit D3 @ 50 000iu vit D3 twice a month.
Like Mercola 2010 http://articles.mercola.com/sites/articles/archive/2010/08/26/this-could-be-even-bigger-than-the-vitamin-d-discovery.aspx, Byron Richards already in 2010 wrote a major review promoting K2 multipurpose: http://www.wellnessresources.com/health/articles/vitamin_k2_bones_cardiovascular_health_blood_sugar_control_cancer_prev/
As a recent BBC review details, “Vitamin K1 has a relatively short half-life and is rapidly cleared from the blood by the liver within eight hours. In comparison vitamin K2 has a longer half-life of up to 72 hours, meaning it remains biologically active in the body for longer. Vitamin K2 is also absorbed better by the body, and is linked to cardiovascular health. It directs calcium to the bones, and prevents it from being deposited where it shouldn’t be, for example arteries and organs, where it can cause harm.
The Kansas Riordan Clinic promotes the Superhuman Duo of D3+K: they point out that ” Because an accurate LD50 for vit D in humans has never been determined (thank God!) most researchers use the LD50 for dogs as an estimate for humans, using a hypothetical human subject weighing 50kg, 110 pounds: in order to reach the LD50 dose, that subject would need to consume over 3,500 of the 50,000 IU D3 caps in a 24 hour period (146 capsules an hour, total 175million iu) in order to have a 50% chance of dying. By conscientiously using vitamin K2 in conjunction with D3, this issue of “metastatic calcium” is thoroughly avoided. Finally, like vitamin D3, strong evidence demonstrates vitamin K’s amazing ability to reduce cancer risk. For example, men taking vitamin K2 mk7 (a naturally occurring long acting form of K2) at 45 mcg a day can statistically reduce their risk of prostate cancer by 60%! That is just one of many cancer risks that are reduced significantly by regular K2 ingestion. As we explore the healing power of higher doses of vitamin D3 at the Riordan Clinic, we have found it prudent to partner the safety and effectiveness of this dynamic duo. For every 5,000–10,000 units of D3 being recommended and tested for, we are recommending 100 mcg of K2 mk7 to be sure and prevent the inappropriate calcification that higher doses of D3 alone could cause.
For the safety of vigorous dose of vitamin D3, the masses of D3 evidence we assembled by August 2015 is that 2million units as a single oral dose does no harm to nonagenarians, nor has over 100 000iu a day for 28 years ie over a billion iu in middle-aged women.
In 2015, Like *Joe Leech and *Hogne Vik , *Angela Pifer nutritionist notes the essensiality of balancing vit D3 with K2 “Vitamin D3 should never be taken alone. Always take a combination Vitamin D3/ Vitamin K2 liquid emulsion, at night for best absorption. This is because vitamin D3 improves calcium absorption across the GI tract and vitamin K2 is the cofactor needed to transfer calcium into your bones, and not your arteries. (Eur J Clin Nutr. 2016 Feb 24. doi: 10.1038/ejcn.2016.3. Steady-state vitamin K2 (menaquinone-7) plasma concentrations after intake of dairy products and soft gel capsules. Knapen, Vermeer ea . Maastricht University, Netherlands. In a previous human intervention study, we observed an improved vitamin K status after 8 weeks of intake of a yogurt fortified with vitamin K2 (as menaquinone-7, MK-7) and vitamins C and D3, magnesium and polyunsaturated fatty acids. It was hypothesized that the added nutrients contributed to this improvement. Here we report on a study in which we compared the fasting plasma concentrations of MK-7 from (a) yogurt enriched with MK-7, vitamins D3 and C, magnesium, n-3 poly unsaturated fatty acids (n-3 PUFA) and fish oil (yogurt Kplus), (b) yogurt fortified with MK-7 only (yogurt K) and (c) soft gel capsules containing only MK-7, For 42 days in healthy men and postmenopausal women between 45 and 65 years of age daily consumed either yogurt K, yogurt Kplus or capsules. RESULTS: The increase in plasma MK-7 with the yogurt Kplus product was more pronounced than the increase in MK-7 with the capsules, reflecting vitamin K status improvement. No significant differences in fasting plasma concentrations of various biomarkers between the yogurts were found. CONCLUSIONS: Dairy matrix and nutrient composition may affect MK-7 delivery and improvement of vitamin K status. Yogurt fortified with MK-7 is a suitable matrix to improve the nutritional status of the fat-soluble vitamins.)
Some recent of the other 5000 K2 refs on Pubmed, apart from the abundant reviews by Garry Gordon, Joe Mercola, Mike Howard, Jeff Dach, Townsend letter, ea , are
Integr Med (Encinitas). 2015;14; 34-9. Proper Calcium Use: Vitamin K2 as a Promoter of Bone and Cardiovascular Health. Maresz K1. International Science and Health Foundation Krakow, Poland Inadequate calcium intake can lead to decreased bone mineral density, thus increase the risk of bone fractures. Supplemental calcium promotes bone mineral density and strength and can prevent osteoporosis. Recent scientific evidence, however, suggests that elevated consumption of calcium supplements may raise the risk for heart disease and can be connected with accelerated deposit of calcium in blood-vessel walls and soft tissues. In contrast, vitamin K2 is associated with the inhibition of arterial calcification and arterial stiffening. An adequate intake of vitamin K2 has been shown to lower the risk of vascular damage because it activates matrix GLA protein (MGP), which inhibits the deposits of calcium on the walls. Vitamin K, particularly as vitamin K2, is nearly nonexistent in junk food, with little being consumed even in a healthy Western diet. Vitamin K deficiency results in inadequate activation of MGP, which greatly impairs the process of calcium removal and increases the risk of calcification of the blood vessels. An increased intake of vitamin K2 could be a means of lowering calcium-associated health risks. “ Calcium Concerns: If at least 32 mcg/d of vitamin K2 is present in the diet, then the risks for blood-vessel calcification and heart problems are significantly lowered, the elasticity of the vessel wall is increased. Moreover, the beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women has been seen in clinical trials. If less vitamin K2 is present in the diet, then cardiovascular problems may arise. Dosing of K2 was supported by a population-based study with 16 000 healthy women aged 49 to 70 years drawn from EPIC’s cohort population. After 8 years ,it showed that a high intake of natural vitamin K2 (ie, not synthetic K2, but not of vitamin K1) was associated with protection against cardiovascular events. For every 10 mcg of dietary vitamin K2 consumed (in the forms of menaquinone 7 (MK-7), menaquinone 8 (MK-8), and menaquinone 9 (MK-9), the risk of coronary heart disease was reduced by 9%. A study on 564 postmenopausal women also revealed that intake of vitamin K2 was associated with decreased coronary calcification, whereas intake of vitamin K1 was not. ” A recent, double-blind, randomized clinical trial investigated the effects of supplemental MK-7, MenaQ7 (NattoPharma ASA, Hovik, Norway) for a 3-year period in a group of 244 postmenopausal Dutch women. The researchers found that a daily dose of 180 mcg was enough to improve bone mineral density, bone strength, and cardiovascular health. They also showed that achieving a clinically relevant improvement required at least 2 years of supplementation.It showed a significant improvement in cardiovascular health as measured by ultrasound and pulse-wave velocity, which are recognized as standard measurements for cardiovascular health. In that trial, carotid artery distensibility was significantly improved for a 3-year period as compared with that of a placebo group. Also, pulse-wave velocity showed a statistically significantly decrease after 3 years for the vitamin K2 (MK-7) group, but not for the placebo group, demonstrating an increase in the elasticity and reduction in age-related arterial stiffening.”
* Nutrients. 2015 Oct ;7;8905-15. Menaquinone-7 Supplementation to Reduce Vascular Calcification in Patients with Coronary Artery Disease: Rationale and Study Protocol (VitaK-CAC Trial).Vossen, Kroon ea Coronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis and is a strong and independent predictor of cardiovascular disease (CVD). Arterial calcification is caused by an imbalance in calcification regulatory mechanisms. An important inhibitor of calcification is vitamin K-dependent matrix Gla protein (MGP). Both preclinical and clinical studies have shown that inhibition of the vitamin K-cycle by vitamin K antagonists (VKA) results in elevated uncarboxylated MGP (ucMGP) and subsequently in extensive arterial calcification. This led us to hypothesize that vitamin K supplementation may slow down the progression of calcification. To test this, we designed the VitaK-CAC trial which analyses effects of menaquinone-7 (MK-7) supplementation on progression of CAC. The trial is a double-blind, randomized, placebo-controlled trial including patients with coronary artery disease (CAD). Patients with a baseline Agatston CAC-score between 50 and 400 will be randomized to an intervention-group (360 microgram MK-7) or a placebo group. Treatment duration will be 24 months. We hypothesize that treatment with MK-7 will slow down or arrest the progression of CAC and that this trial may lead to a treatment option for vascular calcification and subsequent CVD.
* Ugeskr Laeger. 2015 Aug;177:V12140700. Vitamin K2 influences several diseases]. Hey H1, Brasen CL. Lillebælt, Kabbeltoft, In this paper we discuss the evidence of vitamin K2 deficiency which is a factor in several chronic diseases like diabetes, osteoporosis, cancer, inflammatory and cardiovascular diseases. This deficiency is very common in the mentioned diseases although it is rarely treated by clinicians. Randomized clinical trials have shown that patients witr can benefit from vitamin K2 supplement. Further studies are needed to ascertain the effect of vitamin K2 supplement in patients with diabetes and inflammatory bowel diseases.
* Oman Med J. 2014;29;172-7. Vitamin k dependent proteins and the role of vitamin k2 in the modulation of vascular calcification: a review. El Asmar, Arbid ea, American University of Beirut, Lebanon. Vascular calcification, a cause of cardiovascular morbidity and mortality, is an actively regulated process involving vitamin K dependent proteins (VKDPs) among others. Vitamin K is an essential micronutrient, present in plants and animal fermented products that plays an important role as a cofactor for the post-translational γ-carboxylation of glutamic acid residues in a number of proteins. These VKDPs require carboxylation to become biologically active, and they have been identified as having an active role in vascular cell migration, angiogenesis and vascular calcification. calcification.
* Dermatoendocrinol. 2015 Jan;6e968490. Vitamin K: an old vitamin in a new perspective. Gröber U, Reichrath J, Holick MF, Kisters Essen, Germany.& Boston, MA USA. The topic of “Vitamin K” is currently booming on the health products market. Current research increasingly indicates that the antihaemorrhagic vitamin has a considerable benefit in the prevention and treatment of bone and vascular disease. Vitamin K1 (phylloquinone) is more abundant in foods but less bioactive than the vitamin K2 menaquinones (especially MK-7, menaquinone-7). Vitamin K compounds undergo oxidation-reduction cycling within the endoplasmic reticulum membrane, donating electrons to activate specific proteins via enzymatic gamma-carboxylation of glutamate groups before being enzymatically reduced. Along with coagulation factors (II, VII, IX, X, and prothrombin), protein C and protein S, osteocalcin (OC), matrix Gla protein (MGP), periostin, Gas6, and other vitamin K-dependent (VKD) proteins support calcium homeostasis, inhibit vessel wall calcification, support endothelial integrity, facilitate bone mineralization, are involved in tissue renewal and cell growth control, and have numerous other effects.
2016 CHOOSING BREAST SCREENING, BAD DIET/LIFESTYLE ARE OBSESSIVE-COMPULSIVE DISORDERS. SCREENING MAMMOGRAPHY ASSAULT UPDATE : FLOOD OF PROGRESS AGAINST BREAST CANCER/ DISEASE.
NEXT SURE TOUCH CLINIC CAPETOWN 30 April 2016 For those who (despite clinical reassurance, and the evidence against screening for silent breast and prostate cancer as recently again published below in a British Journal) ), still want screening breast imaging, Saturday 30 April 2016 is the next Sure Touch imaging clinic by our Breast Screening Sister (and if required, specialist doctor) for asymptomatic women with well breasts who despite the futility and risks still desire screening breast imaging.
Book at the Natural Wellness Clinic in Grove Bldg Claremont Cape Town (between ABSA on Grove and Cavendish). ph 021 6831465/ 021 6717415 or 0712025274 office hours to book appointments , or email firstname.lastname@example.org, or ph Reyhana 0763910463 . (next Thermography clinic +- June tba ).
UPDATE 22 APRIL 2016: BREAST SCREENING OF WELL WOMEN BY SOUTH AFRICAN MEDICAL SCHEMES : a reminder:
DIAGNOSTIC xray mammography is an invasive DIAGNOSTIC procedure FOR A BREAST LUMP/BLEEDING that irradiates and crushes the breasts; and is therefore universally recommended by independent experts and trials ONLY for women ( with a breast lump) where cancer needs to be excluded; and provided as a free service by the state every 10 years, and by medial schemes as a prescribed medical benefit PMB on demand.
Prof Michael Baum University College London, London responded: “Catch it early, save a life and save a breast’: this misleading mantra of mammography: The one thing every layperson and politician knows with confidence with regard to breast cancer is that you’ve got to ‘catch it early,’ preferably before you can even feel it. It may come as a shock to some readers, but I disagree and there’s such a thing as ‘catching it too early’. Like Peter Gøtzsche in the current edition of the JRSM,1 the global breast cancer screening programme has to be considered a ‘failed experiment.’ I also agree that the screening service as now provided should be closed down. I would go on to suggest that all the human and technological resources released by the closure of the National Health Service Breast Screening Service (NHSBSP), be redeployed into more fruitful areas for enhancing women’s health. That aside we have much to learn from the fact that the experiment, set up in good faith, has indeed failed to live up to our expectations. The mantra, ‘Catch it early, save a life and save a breast’, turns out to be a false promise. Screening may have a borderline effect on reducing cause-specific mortality but does not save lives as judged by the outcome measure of all-cause mortality.2 As far as saving breasts is concerned, the opposite is the truth. Populations of women attending for screening have a greater chance of a mastectomy than any control group.2
The hypothesis being tested in the experiment originated in the last half of the 20th century and was based on the assumption of the log linear kinetics of cancer development with distant dissemination being determined by the size (a poor surrogate for ‘age’) of the cancer. This was considered so self-evident as to have been translated into an ideological expression of faith. Yet, the experiment failed. The national breast screening programmes around the world have provided us with a natural experiment of the greatest historical importance, first, because it failed to deliver and, second, because of the recognition that mammography in asymptomatic women leads to the over-diagnosis of ‘pseudo-cancers’.3
Cancer was defined by its microscopic appearance about 200 years ago. The 19th century saw the birth of scientific oncology with the discovery and use of the modern microscope. Rudolf Virchow, often called the founder of cellular pathology, provided the scientific basis for the modern pathologic study of cancer.4 As earlier generations had correlated the autopsy findings observed with the unaided eye with the clinical course of cancer 100 years earlier,5 so Virchow correlated the microscopic pathology of the disease. However, the material he was studying came from the autopsy of patients dying from cancer.
In the mid-19th century, pathological correlations were performed either on cadavers or on living subjects presenting with locally advanced or metastatic disease that almost always were pre-determined to die in the absence of effective therapy. Since then without pause for thought, the microscopic identification of cancer according to these classic criteria has been associated with the assumed prognosis of a fatal disease if left untreated. There is a syllogism at the heart of the diagnosis of cancer and therefore runs like this; people frequently die from malignant disease, under the microscope this malignant disease has many histological features we will call ‘cancer,’ ergo anything that looks like ‘cancer’ under the microscope, will kill you. I would therefore like to restate the argument, that some of these earliest stages of ‘cancer’ if left unperturbed, would not progress to a disease with lethal potential. These pathological entities might have microscopic similarity to true cancers, but these appearances alone are insufficient to predict a life-threatening disease. If we stand back and take a broader look at nature this shouldn’t be surprising.
Conventional mathematical models of cancer growth are linear or logarithmic, in other words completely predictable at the outset; predicting transition from in-situ phases to early invasive and from early invasive to late invasive over time. Most natural biological mechanisms are non-linear or better described according to chaos theory. The beauty of the tree in full leaf and the symmetry of a sprig of broccoli, reflect their fractal geometry that looks remarkably similar to the appearance of the mammary ducts and lobules under the microscope.6 The rate of growth and the development of the lung along with the fingers and toes in the fetus cannot be described in linear terms. Prolonged latency followed by catastrophe should not be all that surprising.7 We accept the case for prostate cancer, as we know that most elderly men will die with prostate cancer in situ and not die of prostate cancer. In fact, the UK national PSA screening trial (ProtecT) is predicated on that fact with two a priori outcome measures defined, deaths from prostate cancer versus the number of cancers over-detected and treated unnecessarily.8
Further support for this contention comes from other sources. For example, there has been an epidemic of bilateral mastectomies in the USA following the uncontrolled proliferation of MRI scans in the routine work-up of women presenting with a single focus of early breast cancer.9,10 The MRI scan is guilty of unveiling not only latent foci of pseudo-cancers outside the index quadrant but also latent foci harboured in the contra-lateral breast. This is heartbreaking when one considers all the work over three decades and all the patient volunteers in trials of breast conservation.11,12 We now know with the utmost confidence that breast-conserving surgery is a safe alternative to more radical surgery, yet that hard won knowledge is brutally ignored when the surgeon is induced to treat the MRI image rather than the patient. Next, it is worth noting that contrary to all common sense predictions, the increased rate of detection of duct carcinoma in situ has led to an increase in the mastectomy rate for the screened population.2,3 Up to 45% of screen detected cases of duct carcinoma in situ end up having mastectomy because of the multi-centricity of the disease.13 Yet, the paradox is that clinically detected multi-centric invasive breast cancer is relatively uncommon.14 In conclusion, therefore, we can state, with a great deal of conviction, that a large proportion (in the order of 50%3) of screen detected (pre-clinical) foci of breast cancer is not programmed to progress if left unperturbed. This observation is of seismic importance and could set the agenda for breast cancer research for the next decade. If we choose to ignore these observations, because they fail to support our ideological belief system, then we will have missed an opportunity of a lifetime and that would be unforgivable.
The superiority of even ultrasound screening over xray mammography has been shown in women with dense breasts (like most today in our obese society) in Br J Cancer. 2015 ; 112: 998–1004. A multi-centre randomised trial comparing ultrasound vs mammography for screening breast cancer in high-risk Chinese women Shen ea, Chinese women tend to have small and dense breasts and ultrasound is a common method for breast cancer screening in China. However, its efficacy and cost comparing with mammography has not been evaluated in randomised trials. Methods: At 14 centres across China during 2008–2010, 13 339 high-risk women aged 30–65 years were randomised to be screened by mammography alone, ultrasound alone, or by both methods at enrolment and 1-year follow-up. Results: Among the 30 cancers (of which 15 were stage 0/I) detected, 5 (0.72/1000) were in the mammography group, 11 (1.51/1000) in the ultrasound group, and 14 (2.02/1000) in the combined group (P=0.12). In the combined group, ultrasound detected all the 14 cancers, whereas mammography detected 8, making ultrasound more sensitive (100 vs 57.1%, P=0.04) with a better diagnostic accuracy (0.999 vs 0.766, P=0.01). There was no difference between mammography and ultrasound in specificity (100 vs 99.9%, P=0.51) and positive predictive value (72.7 vs 70.0% P=0.87). To detect one cancer, the costs of ultrasound, mammography, and combined modality were $7876, $45 253, and $21 599, respectively.
update: 28 July 2015 Mammography’s $4-Billion Problem Millions of women receive false-positive results annually, and 20,000 are overtreated. by Shannon Firth WASHINGTON — For too many women, breast cancer screening does more harm than good, a researcher said here. Thermography is a non-invasive imaging procedure which uses a heat-sensitive camera to capture an image of the human body. Since we are pretty much symmetrical beings, seeing one breast significantly warmer than the other would be a red flag, suggesting the presence of a heat-generating lesion. The lesion could be an abscess, or increased blood vessels feeding an early tumor, or simply a recent hematoma from injury. In any case, no radiation is used to obtain the image, there is no compression of the breast, and the study can be repeated frequently with no risk of inducing neoplastic transformation. Studies show that thermography can diagnose significant inflammatory disease up to several years before a mammogram shows calcification. Insurance does not pay for this test. Thermography does not diagnose cancer. Nor does mammography. At least thermography is helpful and does no harm. And if a mass is palpated, then excisional biopsy is indicated no matter what the tests show. Common sense needs to prevail.
July 06, 2015 Mammograms Again Found to Have No Impact on Mortality JAMA Intern Med. . Breast Cancer Screening, Incidence, and Mortality Across US Counties Harvard University, Cambridge, Massachusetts Importance Screening mammography rates vary considerably by location in the United States, providing a natural opportunity to investigate the associations of screening with breast cancer incidence and mortality, which are subjects of debate. Objective To examine the associations between rates of modern screening mammography and the incidence of breast cancer, mortality from breast cancer, and tumor size. Design, Setting, and Participants An ecological study of 16 million women 40 years or older who resided in 547 counties reporting to the Surveillance, Epidemiology, and End Results cancer registries during the year 2000. Of these women, 53 207 were diagnosed with breast cancer that year and followed up for the next 10 years. The study covered the period January 1, 2000, to December 31, 2010, and the analysis was performed between April 2013 and March 2015. Exposures Extent of screening in each county, assessed as the percentage of included women who received a screening mammogram in the prior 2 years. Main Outcomes and Measures Breast cancer incidence in 2000 and incidence-based breast cancer mortality during the 10-year follow-up. Incidence and mortality were calculated for each county and age adjusted to the US population.Results Across US counties, there was a positive correlation between the extent of screening and breast cancer incidence (weighted r = 0.54; P < .001) but not with breast cancer mortality (weighted r = 0.00; P = .98). An absolute increase of 10 percentage points in the extent of screening was accompanied by 16% more breast cancer diagnoses (relative rate [RR], 1.16; 95% CI, 1.13-1.19) but no significant change in breast cancer deaths (RR, 1.01; 95% CI, 0.96-1.06). In an analysis stratified by tumor size, we found that more screening was strongly associated with an increased incidence of small breast cancers (≤2 cm) but not with a decreased incidence of larger breast cancers (>2 cm). An increase of 10 percentage points in screening was associated with a 25% increase in the incidence of small breast cancers (RR, 1.25; 95% CI, 1.18-1.32) and a 7% increase in the incidence of larger breast cancers (RR, 1.07; 95% CI, 1.02-1.12). Conclusions and Relevance When analyzed at the county level, the clearest result of mammography screening is the diagnosis of additional small cancers. Furthermore, there is no concomitant decline in the detection of larger cancers, which might explain the absence of any significant difference in the overall rate of death from the disease. Together, these findings suggest widespread overdiagnosis.
2 March 2015: this update says it al about the futility and risks of breast cancer mammography screening:
Breast Cancer Screening: Benefits and Harms:
Breast cancer is the second most common cancer among women in the United States.
BENEFITS OF SCREENING Screening for breast cancer means looking for signs of breast cancer in all women, even if they have no symptoms. The goal of screening is to catch cancers early. Early-stage cancers are easier to treat than later-stage cancers, and the chance of survival is higher. Routine screening for breast cancer lowers one’s risk of dying of breast cancer.
Screening for breast cancer is done by mammography. A mammogram is a special series of x-rays taken of the breast. A doctor looks for any abnormal signs or patterns on the mammogram that might be breast cancer. These signs usually show up on the mammogram before any lump can be felt in the breast. If there is anything unusual on the mammogram, more tests have to be done. These tests can include another mammogram, an ultrasound, or a biopsy. Studies have shown that women who have routine mammograms have 10% to 25% less chance of dying of breast cancer than women who do not have mammograms.
Another possible harm of screening is overdiagnosis. This means finding something on a mammogram that is breast cancer or has a chance of becoming breast cancer, but is such a low-risk type of tumor that it would never have caused any health problems if left alone. Instead, because it was found on mammogram, standard cancer treatment, such as surgery and radiation therapy, is recommended. In cases of overdiagnosis, these treatments are unnecessary and costly and can have both physical and psychological side effects. It is difficult to know exactly how often overdiagnosis happens, but some studies estimate that 1 in 5 breast cancers found on mammograms are overdiagnosed and lead to unnecessary treatment.
12 February 2015 Why I’m Opting out of Mammography JAMA Intern Med. at a routine appointment a few days after my 40th birthday, my gynecologist gave me a prescription for a mammogram. There was no discussion, no explanation. Just a slip of paper, handed to me without a word as I left the examination room. When I asked the doctor what she’d just given me, she told me it was an order for a mammogram. I could call the number to schedule an appointment. “Wait—why should I get a mammogram?” I asked. “Because it could save your life.” Her voice conveyed a note of impatience… read on..
24 Jan 2015 early diagnosis ( by screening the well), and treatment of pre-cancer of eg breast and prostate is increasingly discredited as dangerous, especially for women at ~10years younger prime-of life ( and much higher risk than men) due to menopause. .
This is the same cancer rate found in random adults killed in accidents. SO WHAT MAMMOGRAPHY SCREENING OF WELL BREASTS ACHIEVED EXCEPT COUNTLESS IRRADIATION, SURGERIES AND THUS STRESS?
Commentary: Prof Peter Gøtzsche Nordic Cochrane, Denmark. Int. J. Epidemiol. Jan 2015: SCREENING- A SEDUCTIVE PARADIGM THAT HAS GENERALLY FAILED US: “Screening healthy people has face value and great public and political appeal. It looks so simple, and yet screening is fraught with difficulties. These start already with the terminology, and common slogans like, ‘Catch the disease early, before it has produced any symptoms!’ are misleading on two counts.
First, disease means lack of ease, which is not what we understand by being healthy; but people who work with screening tend to forget that they deal with healthy people. For example, women being invited to mammography screening are often called patients in scientific articles. The second error is the assumption that the disease is caught early. That is rarely the case, and breast cancer is again a good example. If we assume that the growth rate for a particular cancer is constant, then the women have harboured the cancer for 21 years on average before it is large enough to be detected by mammography screening.1 Finding precursors to cancer is of course an entirely different matter.
A third problem with screening is that it always causes harm. Sometimes it also leads to benefits, and sometimes the benefits are sufficiently large to outweigh the harms. The main focus in screening trials should therefore be to quantify the harms, but this has rarely been the case, if ever. Screening trials focus on disease-specific mortality, which may seem natural, but it is the wrong outcome. Screening leads to overdiagnosis, and interventions that are beneficial for real patients can be lethal for healthy overdiagnosed people. Radiotherapy of overdiagnosed women may kill at least as many as those who are spared dying from breast cancer by attending breast screening.2
Total mortality should therefore be the primary outcome in screening trials of mortality, and Saquib et al. report a systematic review in this issue of the journal that aimed at clarifying whether screening lowers total mortality for diseases that carry a high disease-specific mortality.3 They focused on cancer, cardiovascular diseases, type 2 diabetes and chronic obstructive pulmonary disease. They did not find any screening trials for hypertension or chronic obstructive pulmonary disease. Disease-specific mortality was reduced with ultrasound for abdominal aortic aneurysm in men, mammography for breast cancer and faecal occult blood test and flexible sigmoidoscopy for colorectal cancer, but the risk ratio point estimates for all-cause mortality were all very close to 1.00 (range 0.98–1.03).
Screening proponents often say that disease-specific mortality is the right outcome, arguing that in order to show an effect on total mortality, trials would become unrealistically large. I believe this argument is invalid, for both scientific and ethical reasons. We do randomized trials in order to avoid bias, and our primary outcome should therefore not be a biased one. Drug interventions are usually more common in a screened group, and they tend to increase mortality for a variety of non-disease related reasons.4
From an ethical perspective, it is problematic to screen the whole population in a certain age group without knowing whether this makes people live longer, while knowing almost certainly that it makes people less happy. It took 50 years after the first randomized trial of mammography started before we knew what the psychological consequences are of the many false-positive findings.5 A specially designed questionnaire was developed using focus groups and women who had attended screening were followed up for 3 years. Even after so long a time, those who had experienced a false-positive diagnosis had an anxiety level (and other psychological problems) that fell between that for women with breast cancer and women who had always been told they did not have cancer. This study showed for the first time that the psychological harms of breast screening are substantial and long-lasting, and they affect a huge number of healthy women, as the cumulative risk of a false-positive result after 10 mammograms ranges from about 20% to 60%.6 Added to this comes the psychological harm inflicted on all the overdiagnosed women who do not know that they are overdiagnosed but think that they suffer from a fatal disease. It is therefore pretty clear that any utility analysis that takes the psychological harms of breast screening into account will come out negative, as was recently reported by the Swiss Medical Board.7
It is worth noting that when screening does not work, it might be because beneficial effects are outweighed by harmful ones. Diabetes drugs, for example, are approved on the basis of their glucose-lowering effect without knowing what they do to patients. And the only large trial of tolbutamide ever performed was stopped prematurely because the drug increased cardiovascular mortality.4 Rosiglitazone was once the most-sold diabetes drug in the world, but it was taken off the market in Europe in 2010 as it causes myocardial infarction and cardiovascular death; and pioglitazone has been linked to heart failure and bladder cancer.4
Screening is popular, but we need to be much more careful in the future when we contemplate approaching healthy people with our screening tests, and should demand much stronger evidence than when we treat patients.”
September 16, 2014 — A U.K. clinical trial examining whether mammography screening should be offered to a broader range of women must be halted due to ethical and medical concerns, according to a letter published in BMJ by a group of longtime opponents to breast screening. But not everyone agrees, and the controversy looks set to continue. In a strongly worded letter published (BMJ) on 16 September, a group led by Dr. Susan Bewley raised concerns about the U.K. age-extension trial, which is examining whether the age range for screening should be extended to both younger and older women. They challenge the design of the trial as well as the qualifications of its chief investigator, calling the study an “out of control trial with ineffective oversight.”“Our concerns relate to the science and ethics of this trial. Women should always be told the full facts — here they are unwittingly participating in a research trial without fully realizing that the harm/benefit ratio is uncertain,” Bewley said. “There is no overall mortality benefit from breast screening at any age if you look at the Nordic Cochrane review — only a reduction in breast cancer mortality.”
|Age, y||No. of Breast Cancer Deaths Averted With Mammography Screening Over Next 15 y||No. (95% CI) With ≥1 False-Positive Result During the 10 yc||No. (95% CI) With ≥1 False Positive Resulting in a Biopsy During the 10 yc||No. of Breast Cancers or DCIS Diagnosed During the 10 y That Would Never Become Clinically Important (Overdiagnosis)d|
|40||1–16||6,130 (5,940–6,310)||700 (610–780)||?–104e|
|50||3–32||6,130 (5,800–6,470)||940 (740–1,150)||30–137|
|60||5–49||4,970 (4,780–5,150)||980 (840–1,130)||64–194|
Invisible Risks, Emotional Choices — Mammography and Medical Decision Making Lisa Rosenbaum, M.D. cardiologist & journalist N Engl J Med October 16, 2014: in 1993, frightened New York City parents agitated for asbestos removal from schools. As often occurs, public fear trumped expert risk assessment; the parents’ demands were met, the victory was celebrated, but then the celebration crashed. It turned out that removing the asbestos would mean closing the schools for weeks, disrupting parents’ lives. “As the costs of the removal came on-screen,” writes behavioral economist Cass Sunstein, “parents thought much more like experts, and the risks of asbestos seemed tolerable: Statistically small, and on balance worth incurring.”1
It is partly because our perceptions of risk are so influenced by our changeable emotions that we turn to experts to perform cost–benefit analyses. From environmental regulations to nuclear energy, such expert assessments inform policies meant to improve public health and welfare. We would not ask airline passengers to create standards for aviation safety or car owners to optimize fuel-emission standards, and in medicine, too, we still depend on expert-generated guidelines. Increasingly, however, in this era of patient-centered care and shared decision making, those guidelines emphasize the role that patient preference should play in the weighing of risk and benefit for any given evidence-based recommendation. This approach, with virtue on its side, is driven by the aspiration that we can, with the proper tools, empower patients to think like experts. But can we?
Many medical decisions involve considerable uncertainty and complex tradeoffs, but none seem to highlight the tension between emotions and risk assessment more than mammography screening. Although the U.S. Preventive Services Task Force (USPSTF) recommended in 2009 that women under 50 years of age not undergo routine mammography screening, and that those between 50 and 75 years of age be screened less frequently, screening rates have apparently held steady or perhaps even increased. There are many possible reasons for this trend: physicians’ habits, conflicting guidelines, medicolegal concerns, radiologists’ preference for the status quo, and the mandating of screening coverage for women of all ages in the Affordable Care Act. But I suspect that the trends also reflect the powerful role that emotions play in both reinforcing women’s commitment to screening and the challenge of communicating the potential harms of mammography.
Consider a discussion with a 45-year-old woman with no family history of breast cancer about the most likely harm of screening: a false positive result. Maybe you say, “For someone like you, there is around a 50% chance that if you have regular screening over the next 10 years, you will have a false positive result. That could lead to repeat testing, potentially including a biopsy, and lots of worry and anxiety.”2 But though doctors striving to reduce unnecessary testing tend to emphasize the psychological stress involved, this possibility does not seem to loom large for women facing this decision.
Perhaps these results reflect the likelihood that, when facing tough tradeoffs, we anticipate and try to avoid regret, rather than anxiety. Despite the demonstrable harms on the population level, cancer screening rarely begets regret for the individual. As Ransohoff and colleagues have written about the persistence of prostate-cancer screening, “the screening process is one without negative feedback. A negative test provides reassurance. A positive one is accompanied by gratitude that disease was caught early. And a false positive test, regardless of the distress it may cause, is nevertheless followed by relief that no cancer was ultimately found.”5 So women who have had false positive mammograms may spend the rest of their lives worrying that they are at heightened risk for breast cancer. But they are not left with regret about having had the test in the first place.
What about the risk of overdiagnosis — being diagnosed with and treated for a tumor that would never have become clinically significant? The potential toxic effects of treatments, ranging from chemotherapy and radiation to lumpectomy and mastectomy, make overdiagnosis the greatest potential harm of mammography screening. Though overdiagnosis has been notoriously difficult to quantify, a recent analysis of data on mammography screening over the past 30 years suggests that of all breast cancers diagnosed, 22 to 31% are overdiagnosed.6 Nevertheless, there are few risks of this magnitude that are more “off-screen” than overdiagnosis.
The first challenge in conveying this risk to women is that many are simply unaware that overdiagnosis occurs. One survey showed that only 7% of women believed that there could be tumors that grow so slowly that an affected woman would need no treatment; another study showed that women found the concept confusing even after a brief educational intervention. After being educated, women thought the information should be considered in decision making, but most believed it would not affect their own intent to be screened.3,7
This disconnect between awareness and intent speaks to the fundamental challenge of conveying the potential harms of mammography screening. That is: we do not think risk; we feel it. As research on risk perception has shown, we are often guided by intuition and affect.8 For example, when our general impressions of a technology are positive, we tend to assume that its benefits are high and its risks are low. We estimate our personal risks of disease not on the basis of algorithms and risk calculators, but rather according to how similar we are, in ways we can observe, to people we know who have the disease. And when we fear something, we are far more sensitive to the mere possibility of its occurrence than its actual probability.
That may be why overdiagnosis does not resonate emotionally. We do not see women walking around with “an overdiagnosis.” Instead, we see breast-cancer survivors. We do not hear people complaining about having endured radiation, chemotherapy, and a lumpectomy. What we hear instead is, “Thank goodness I had a mammogram and caught it early.” Our relatives do not eye us critically when we get a mammogram that reveals a nascent tumor. But people shake their heads and say, “I wish she had taken better care of herself,” when we are diagnosed after not having been screened. Thus, we can be educated about overdiagnosis. We can refine our estimates about its likelihood and incorporate them into our recommendations, as the USPSTF did in 2009. But it is hard to summon fear of a risk that remains invisible.
So how do we balance the goal of engaging women in decision making with the reality that emotions play a powerful role in shaping our understanding of benefit and risk? Some experts emphasize the need to address sources of misperception that inform beliefs far outside clinical encounters. Researchers at Dartmouth, for example, have described the misleading nature of various screening-advocacy campaigns. One advertisement by the Komen Foundation, for instance, features a photo of a beautiful young woman, with a caption reading, “The 5-year survival rate for breast cancer when caught early is 98%. When it’s not? 23%.”9 Though 5-year survival rates, because of lead-time bias and overdiagnosis, do not actually tell you whether the test saves lives, the visceral appeal of “catching something early” easily eclipses the difficult mental calculations one must undertake to figure out why early detection does not necessarily mean living longer.
The problem is that once impressions have formed, whatever their source, educational efforts to address misperceptions often fail and can even backfire. In a recent randomized trial evaluating approaches to vaccine education, for example, researchers found that, among parents least likely to vaccinate their children, exposure to information emphasizing that there is no link between vaccines and autism mitigated misperceptions but nevertheless further reduced their intention to vaccinate.10 Indeed, the fact that sound scientific information that challenges beliefs can simply intensify those beliefs has been recognized by cognitive psychologists for decades. What was more disappointing in this study was that more creative attempts to engage parents emotionally, such as using images or narratives of children dying of measles, not only failed to increase vaccination intent but also cemented some parents’ conviction that there is a link between vaccines and autism.
If there is tension between belief and sound medical information regarding vaccines, for which the benefits so clearly outweigh the risks, the tension is only heightened for decisions with more complex tradeoffs. The vaccine study thus raises two key challenges for the profession.
The first is empirical. As the locus of decision making shifts toward the patient, this study reminds us how little we know about how beliefs inform interpretation of medical evidence — or about how to negotiate those beliefs in pursuit of better health. Closing this empirical gap is daunting. Not only does each person have his or her own belief system, but the particular beliefs that are relevant for a decision regarding, say, elective percutaneous coronary intervention or palliative chemotherapy may be quite different from those relevant to childhood vaccination or mammography screening. Moreover, even though it is more practical and financially feasible to conduct a study that looks at how interventions affect knowledge and intent, what we really need are long-term studies of how new approaches to sharing information affect downstream behaviors and outcomes.
Which brings us to the second challenge, more ethical than empirical: How do we balance the need to honor preferences and values with the imperative to translate our evidence base into better population health? Our current default, particularly since medical recommendations are increasingly debated publicly, is to emphasize that decisions are “personal.” After the 2009 guidelines were published, the Obama administration and many physician leaders were all over the news reminding us of the importance of personal preferences. But even as more data accrue, including a recent review suggesting that the harms of mammography are greater than we once thought and the benefits fewer,11 the message we hear is not “Let’s do fewer mammograms.” Rather, it is “Let’s honor patients’ preferences.”
Though we certainly need to be sensitive to patients’ values, it is often hard to distinguish values from an emotional understanding of risk. Consider the decision to initiate statin therapy for primary prevention of cardiovascular disease. One patient, an avid tennis player, may recognize the potential for improved cardiovascular health but feel that the prospect of myalgias simply outweighs any potential benefit. That is a preference. Another patient hates drug companies and therefore believes that statins must lack cardiovascular benefit and be highly likely to cause myalgias and liver disease. That is an emotional understanding of risk. Both patients arrive at the same choice, but should we really celebrate them as equally informed decisions?
The tangled nature of emotions and values is particularly relevant to mammography screening, as evidenced in qualitative research done since the 2009 guidelines were released. One study explored the beliefs and attitudes of an ethnically diverse sample of women in their 40s. Though many were unaware of the guidelines, the researchers found that educating them about the new recommendations strengthened rather than diminished their commitment to screening. Women also expressed fears that the guidelines were an attempt by insurers to save money and keep them from getting the care they needed. Many women, expressing their abiding conviction that mammograms save lives, said they would have “no use” for a decision aid and viewed the weighing of benefits and harms as “irrelevant.” In fact, many said they wanted to be screened more than once a year and beginning before the age of 40 years. Finally, many believed that it was unjust that laywomen had been left out of the guideline-development process and the weighing of potential benefits and harms that it entailed.12
Such responses echo a broader debate among leading scholars of risk perception about whom we should rely on to evaluate risk. Some, such as Sunstein,1 recognizing our general difficulties in thinking about probabilities, argue that this task ought to be left to experts who can create policies to maximize public welfare. But the psychologist Paul Slovic has argued that the very concept of risk is subjective. Whereas experts tend to conceive of risk as “synonymous with expected annual mortality,” Slovic reminds us that riskiness means more to people than mortality rates.13
Undoubtedly, the recognition of the affective nature of risk perception is critical to the physician’s role in helping patients live longer, higher-quality lives. But even if we can, in some general way, address misleading statistics that drive inflated perceptions of the benefits of mammography, what do we do about the 38-year-old woman who insists on annual screening because she just lost her best friend to breast cancer? Or the 43-year-old with fibrocystic breasts who last year had a false positive mammogram and is now convinced her risk is even higher? Is there some hierarchy of emotional reasoning dictating that certain causes of heightened fears are more acceptable than others? Or because we know it is often impossible to tease out sources of belief, much less rank them, is a better approach the more paternalistic one: definitive guidelines on which physicians base their recommendations, with less emphasis on the role that patient preference ought to play?
One of the hallmarks of heuristic reasoning, as emphasized by Daniel Kahneman,14 is that faced with a hard question, we answer an easier one instead. In some sense, then, as a profession, we have fallen into a collective heuristic trap. Rather than confront these thorny ethical questions head on, we have answered an easier question: Should we respect patients’ values and preferences? The right answer will always be yes. The much harder question is how to balance that respect with our professional responsibility to use our expertise to translate clinical science into better population health.
Defaulting to patient preference in the face of uncertainty has become the moral high ground. But it is as much our job to figure out how to best help our patients lead healthier lives as it is to honor their preferences. No matter how well we can define the tradeoffs of a medical decision, the threshold at which we decide that benefits outweigh harms is as subjective as individual patients’ perceptions of those tradeoffs. But this recognition does not stop us from making rigorous attempts to quantify the tradeoffs, any more than it should stop us from trying to better understand how our patients’ feelings and beliefs inform their understanding of those numbers, consequent behaviors, and health outcomes. As Slovic has emphasized, experts’ efforts to communicate risk will fail in the absence of a structured two-way process. “Each side, expert and public, has something valid to contribute,” he notes. “Each side must respect the insights and intelligence of the other.”13
“Hello , What are you doing to detox your patients on a daily basis? We live in a crazy world where nutritional supplements with little or no clear risks to consumers are seized/ restricted, but Authorities drag feet on stopping the use of a proven toxin like BP-A found as a coating inside of most canned goods. Please understand that Randy Jirtle at Duke has shown that BP-A made healthy brown Agouti mice become obese, yellow and diabetic! That effect led to an epigenetic change, which will persist for generations and was shown to be an epigenetic change in methylation.Plan to protect yourself with lots of methylation support. I take my Beyond B12 sublingual product that provides Methyl Folate and Methyl B12. Please know virtually everyone tests positive for BP-A in urine much of the time, as we have great difficulty in avoiding this poison in our daily living. Yet authorities ignores the dangers although they finally are doing something to protect babies a little.How can anyone practice effective medicine today and ignore the toxin burden we all carry. Remember when I got out of training in 1958 normal sperm count was 140 million; today few have 40 million. I detox daily with my “Power Drink” and PEMF and I definitely show real benefits even at age 79.“BPA has been linked to possible health problems of the brain, breast and prostate. In 2008, the environmental group Natural Resources Defense Council asked the FDA to ban use of the chemical because of what it termed “serious adverse health effects.”In 2011, the American Medical Association deemed BPA an “endocrine-disrupting agent” and urged that “BPA-containing products with the potential for human exposure be clearly identified.” The FDA said it continues to evaluate the safety of BPA-containing products.”http://online.wsj.com/article/SB10001424127887323740804578600113164806902.html?mod=djemHL_t
Tying up Garry Gordon’s two themes above is obviously the fact that , as in eg the USA ARED (Centrum) trial, the Lemon-Rollo McMaster supermouse trials and the Scottish Highlands, and China supplement trials, multisupplements are longterm (especially with vigorous levels of vitamins C and D and magnesium) both antioxidant, insulin sensitizing, methylating, Nitric-oxide promoting and (heavy metal) detoxicants- ie promote healthspan and suppress degenerative diseases and infection. . .
UPDATE 18 OCT 2014: more arguments against screening mammography from UK and Canada:Curr Oncol. Oct 2014; 21(5): 210–214. Reflections on screening mammography and the early detection of breast cancer. A Countercurrents Seriesa S.A. Narod, MD *Women’s College Research Institute, Women’s College Hospital, Toronto, ON.A little learning is a dangerous thing.— Alexander Pope, An Essay on CriticismIn the stormy aftermath of the recent publication of results from the 25-year Canadian National Breast Screening Study (nbss)1, various opinions questioning the validity of the study’s results have been expressed2–7. I was a latecomer to the study. In 2005, I was charged with oversight of the final record linkage and the statistical analysis and interpretation of the final data set. Dr. Anthony Miller has been my mentor since 1987. Our first joint paper, on screening for cervical cancer, was published in 19918. I chose not to respond to individual criticisms, but instead to collect my thoughts and to try to explain why the study authors saw no benefit from screening.Most of the criticism from the radiology community focuses on issues of study design (which they claim was inadequate) and on the quality of the mammography (which they also claim was inadequate). Cancer survivors bolster those criticisms with testimonials and appeals to common sense. Supporters of the study are drawn from the public health community, and they tend to focus on overdiagnosis and health economics.The report at issue is not the first emerging from the nbss. Earlier reports9,10 were criticized for not having allowed adequate follow-up time. But the 25-year results resemble the early results, and the authors are no longer criticized for premature disclosure. None of the first-generation critics have acknowledged the consistency; instead, they look elsewhere and point out other weaknesses. They claim that high-risk women were assigned to the mammography arm in violation of the principle of randomization. In his bestseller The Emperor of All Maladies, Siddhartha Mukherjee says, as a matter of fact, that high-risk women were assigned surreptitiously to the mammography arm, which explains the lack of observed benefit11.The most recent nbss report1 tallied the breast cancers that occurred in each of the two study arms after the screening period ended (that is, between years 6 and 25), counting 2584 cancers in the screening arm and 2609 cancers in the control arm. If the screening arm had been enriched for women at “high risk,” that enrichment must have been performed in a peculiar fashion, using only risk factors that have a transient effect. Perhaps Dr. Mukherjee would care to explain what those factors were. It follows that the excess of cancers seen in the screening period (years 1–5: 666 vs. 524) was a result of early diagnosis and not from stacking the deck.In any case, compelling evidence against the criticism of assignment of high-risk women to the screening arm is provided in the most recent analysis1, and that criticism is no longer raised (although no one has retracted or apologized). Instead, critics now insist that many women with palpable lesions were sent directly to the screening arm by duplicitous research assistants. There is no reason to believe that such actions (which would involve a national conspiracy of dozens of coordinators who spoke two official languages) were taken, but even if they had been, the study and its conclusions would not necessarily be invalidated. Even if all the women with prevalent cancers had been shunted to the screening arm, the situation could still be remedied by ignoring all cancers found at the first screening round (prevalent cancers) and focusing instead on the incident cancers. Such a strategy is not uncommon in screening studies. In the nbss, no woman had the opportunity to “cross the floor” from one study arm to the other after initial assignment. Therefore, if we exclude all prevalent cases from the analysis and focus on women with no cancer at study entry, we can re-evaluate the benefit of mammography thereafter. The hazard ratio for death from breast cancers detected in screening rounds 2–5 was 0.90 (95% confidence interval: 0.69 to 1.16;p = 0.40).But what about crossover? It is claimed that a certain proportion of the women in the control arm—perhaps as high as 20%—opted for screening off-study, in particular after the screening period was over. That crossover will, some say, eclipse a benefit of screening that might otherwise have ensued. That is, the benefit of mammography (which might well have been substantial) was nullified by a subcohort of independently-minded women who went for mammography at the end of the 5 years. That speculation is fanciful, but if true, should be welcomed, because it can now be said to a patient who, at age 40, requests a mammogram, that there is no hurry; she can come back in 5 years for a mammogram and achieve the same net benefit. And when she comes back at age 45, she can be reprieved again until age 50.Crossover is a form of contamination that results in misclassification of the exposed and unexposed groups. In a trial, it will tend to bias the result toward the null. The best way to avoid misclassification is to randomize the patients after they agree to participate—as the nbss did. In contrast, in the Swedish two-county trial (discussed in more detail a little later in this article), the subjects were randomized by intention-to-treat—that is, by whether they received or did not receive an invitation to mammography12–15. Of the 78,085 women in Sweden who were offered screening, 69,645 accepted and 8440 declined. In effect, then, 8440 women in the Swedish study were de facto misclassified (versus an undisclosed number of hypothetical crossers-over in the Canadian study). The proponents of the Swedish study do not see that misclassification as a shortcoming, but instead use it to buoy their argument in favour of screening. They say that if everybody invited for screening came for screening, then the protective effect would have been more profound. In the Swedish study, all women in the control group were offered a screening test after the screening period ended (a reasonable thing to do); but those authors were not criticized for “contaminating” their study.
The second issue raised concerns the quality of the mammography. After all, the nbss tests were completed 30 years ago using 30-year-old technology. I still wonder how things might have been done differently. Mammography screening identified 212 women with breast cancer who would otherwise have been missed. They had cancers that were, on average, 1.4 cm in size, with 67% being node-negative. The survival of those women was very good. At the end of the study period, 170 women with a nonpalpable mammography-detected breast cancer were alive or had died of other causes. How many of those lives did screening save? Fifty? Twenty-five? Ten? Unfortunately, all we can say is that the number was too few to be noticed. If a significant number of those 170 lives had, in fact, been saved, surely the difference between study arms would have been noticeable. Breast cancer deaths numbered 180 in the mammography group and 171 in the control group. Perhaps some of the survivors believe that their lives were saved. They might perhaps have written a letter to the editor of their local newspaper extolling the virtues of mammography. But 42 women with a nonpalpable mammography-detected cancer died (none of whom has written a letter to the editor).
I am also among the authors of several publications on the benefits of screening by magnetic resonance imaging (mri) in high-risk women16–18. Those studies were greeted as successes, given that they demonstrated how, with the use of mri, breast cancers could be downstaged. Those studies were accepted by the radiology community as being supportive of screening. Whether mri reduces mortality has not yet been shown. I cannot predict whether mri screening will be effective in reducing mortality 10 years down the line, but I fully expect that if a mortality benefit fails to materialize, the studies will be criticized for using 30-year-old equipment and a poor study design.
Much of the criticism of the nbss has come from Drs. Daniel Kopans and László Tabár, and fellow travellers such as Siddhartha Mukherjee and Patrick Borgen2–7,11. They use the Swedish two-county trial as evidence of a good study that supports the use of mammography and quote a 30% reduction in mortality. Naturally, they do not criticize their canonical study, but it is time to take a closer look.
In the nbss, women were randomized on an individual basis after they had attended the study centre. The result was two groups of equal size and 100% compliance with the first screen. In Sweden, the two counties were divided into 19 geographic strata that were then divided into either 2 blocks (Östergötland) or 3 blocks (Kopparberg). The resulting 45 blocks were randomized, and women in more than half the blocks were sent a letter of invitation to screening. Of the 59% of women who received an invitation, 89% came for the first screen and 83% came for the second screen14.
The Canadian women were offered 5 mammograms 1 year apart. The Swedish women were offered mammograms every 2 years (ages 40–49) or every 3 years (ages 50–74) for up to 8 years. They underwent fewer screens (Table i). The cancers detected by mammography in Canada were similar in size to those detected in Sweden (Table i), but the size of the cancers occurring in the control group were very different. Those comparisons suggest that physical examinations or breast cancer awareness (or both) were important contributors to the size of cancers detected in Canada. A diminution of cancer mortality would not be expected to be associated with a 0.2 cm mean difference in tumour size, but might be expected with a net reduction of 0.7 cm in size19. Of the cancers detected in the screening arm of the Canadian trial, 68% were palpable. That fact has been a source of criticism. But a physical examination was not conducted as part of the screening protocol in Sweden, and the comparable number of palpable tumours was not given. Therefore, given the much longer mean time between screening visits in Sweden, and the high proportion of women in the screening arm that were never screened, I estimate that between 70% and 80% of the cancers in the mammography arm in Sweden would have been palpable and could have been detected by physical examination—had it been done. The fact that the relevant number is not given is a critical lapse. Suppose, for the sake of argument, that 100% of the cancers detected in the screening arm in Sweden were in fact palpable (not a gross exaggeration). What then would be the point of mammographic screening? And if that number (the palpable fraction) is not available, how can the results be judged? Neither the Swedish nor the Canadian trial can exclude the possibility that the benefit from invitation to mammography might have been restricted to women with palpable cancers.
A comparison of key parameters in the Canadian National Breast Screening Study (nbss) and the Swedish two-county trial
The Canadian study reports the number of cancers detected in the follow-up period after the end of the screening period and the number of subsequent deaths from breast cancer. From year 6 to year 25, 2584 incident cancers occurred in the screening group, resulting in 298 deaths (11.5%), and 2609 incident cancers occurred in the control group, resulting in 321 deaths (12.3%). Those data are important because they confirm that, in the absence of screening, the cancer incidence and mortality are equal in the study groups. Where are the comparable numbers for the Swedish study? Again, they are not given. But in looking at the extraordinary Figure 1 from the most recent report of the Swedish study12, the mortality curves are seen to continue to separate at 25 to 29 years after the initiation of screening, and long since screening had stopped.
Tabár and colleagues ask readers to believe that the benefits of mammography are everlasting (or at least for 20 years beyond the end of screening). They make that claim despite having no surety about whether the deaths from breast cancer in years 25–29 were the result of cancers diagnosed during the screening period or diagnosed after screening had stopped. They claim that most of the deaths from breast cancers diagnosed in the control arm occurred more than 10 years after diagnosis. Thus, the reader is asked to accept that a mean of 2.3 mammograms obtained in year 1–7 are more likely than a baseline imbalance in breast cancer risk to lead to a reduction in breast cancer mortality of 30% in years 25–29!
The incidence and mortality rates corresponding to cancers that were diagnosed after the screening trial was stopped are unavailable. Seeing the survival curves corresponding to cases detected in the screened and unscreened cohorts would be interesting. In the nbss, most cancer deaths occurred, as expected, within 10 years from diagnosis1. When the nbss was challenged as to having achieved an even balance in the study groups, the authors provided the relevant data. The Swedish authors should do the same. Patrick Borgen has stated that the nbss is the “worst clinical trial ever done”5—an extraordinary statement. Either he has devoted his life to poring over medical tracts with the zeal of a Talmudic scholar, or he is speaking nonsense. But refuting his claim is easy: it takes merely the time required to read the Swedish papers.
Once the facts are accepted (that screening mammography fails to do what it was intended to do, and that overdiagnosis is real and substantial), then the most interesting questions can begin to be addressed. Did the nbss fail because mammography is not a sufficiently sensitive imaging technique? Or has the screening community been working under false premises?
Consider sensitivity. Proponents of mammography say that the technique is currently better than it was in the 1980s, largely because it is more sensitive. (Specificity is also important, but is not at issue here.) They argue that “the more sensitive, the better.” The earlier a cancer can be identified and managed, the better. The smaller, the better. But those contentions generate an interesting paradox. Consider a woman with a small early-stage breast cancer. The recommendation is that this woman be followed with annual bilateral mammography for 5 or more years to identify recurrences and contralateral cancers20. That recommendation is based on the knowledge that the risk of contralateral cancer is between 0.5% and 0.8% annually21 and that a diagnosis of contralateral cancer is associated with an increase in mortality from breast cancer22. (It has not been shown that screening for contralateral cancer reduces mortality.) But mri is a much more sensitive screening tool than mammography, and by using mri in that setting, a small contralateral breast cancer can be identified in 4% of women with newly-diagnosed breast cancer23. And yet routine mri of the contralateral breast is not recommended, because it has not been shown to improve survival. Instead, the recommendation for follow-up with annual mammography continues. The paradox is this: If 8 years’ worth of incident breast cancers can be identified in one shot, why bother to pick them up in dribs and drabs? The mri-detected occult lesions are understood not to be clinically meaningful because they do not adversely affect mortality (overdiagnosis); however, if a similar lesion were to be found as a primary cancer in the ipsilateral breast, the radiologists insist that it is clinically meaningful. Once the paradigm that an increase in sensitivity increases overdiagnosis is accepted (that is, not all lesions are clinically meaningful), then it is the responsibility of clinicians to try to determine the ideal level of sensitivity.
The nbss has been berated for working with 30-year-old machinery, but I think that the greater problem is that clinicians are still working under 30-year-old assumptions. How much is really known about the relationship between size and survival? How confident is our community about early detection? It is universally accepted that tumour size and survival are inversely related for women diagnosed with palpable breast cancer24. That understanding is the rationale for early detection by mammography or other means. But it does not logically follow that a decrease in tumour size will necessarily lead to a decrease in mortality.
Consider two analogous situations. First, among women with breast cancer who experience a local recurrence, the strongest predictor of death is a short time from diagnosis to local recurrence25. However, that finding does not imply that a further shortening of the time from diagnosis to recurrence through intensive imaging would worsen survival. Second, studies of children with neuroblastoma noted that the children diagnosed in the first year of life experienced much better survival than those diagnosed thereafter26. That observation encouraged physicians to consider that screening for neuroblastoma by measuring urinary metabolites would increase the proportion of children diagnosed in the first year and thereby reduce mortality. The resulting clinical trial unfortunately found no benefit27. Neuroblastoma with a favorable prognosis is detectable by screening, but those cases are associated with a very high rate of spontaneous regression or maturation of the neuroblastoma into benign ganglioneuroma. Very few cases of neuroblastoma detected by screening have unfavourable biologic features such as N-Myc amplification28.
The relationship between breast cancer size and survival is not fixed, and the slope of the curve that defines the relationship varies according to the stage and pathologic features of the breast cancer24. The strongest relationship is seen with large cancers and node-positive cancers29. The relationship is attenuated among women with triple-negative cancers, with her2 (human epidermal growth factor receptor 2)–positive cancers, and with BRCA1-positive cancers19,30. Size does not predict mortality well for women with nonpalpable cancers29. Is it possible that there are additional categories wherein the size–survival relationship does not hold, and that eventually every woman with breast cancer will be able to be assigned to one of those categories? If more specific categorization were to be possible, then there would be no expectation of benefit from early detection—through mammography or any other means. In statistical terms, the question is “Are there variables n1, n2, n3, … nx, such that, after adjusting for n1, n2, n3, … nx in a follow-up study, size is no longer predictive of survival?” For example, in a study of 5423 women with cancers of less than 2.0 cm, tumour size was not predictive of survival after adjustment for grade, hormone receptor status, and her2 expression30. Those data suggest that, as the mean size of breast cancers in a population diminishes, further reductions in size can achieve only marginally less benefit. The lesson of mammography should be used to rethink the fundamentals of breast cancer and its natural history so that planning can commence for the experiments and clinical studies that will lead to better outcomes in the future.
Curr Oncol. Oct 2014; 21(5): 215–216. re: Reflections on screening mammography and the early detection of breast cancer Baum, MD ChM* *Professor Emeritus of Surgery & Medical Humanities, University College, London, U.K.
I welcome this opportunity to comment on the piece by Dr. Steven Narod in this issue of Current Oncology. His commentary systematically responds to, and rebuts, the near-hysterical reactions to the recent publication of the 25-year follow-up results of the Canadian National Breast Cancer Screening Study1. I admire his restraint in the face of criticisms that go way beyond the boundaries of polite scientific disputation.
Much of the criticism the authors of the trial have faced goes so far as to accuse them of being guilty of scientific misconduct and fraud. Those charges are libellous, but I’m sure that Narod et al. are wise enough not to resolve their differences in a court of law, but simply to open their books to scientific scrutiny, in a way that fair-minded clinicians can judge who are the real culprits. Narod has achieved precisely that end in his timely and measured response. My only criticism is minor … in that he doesn’t go far enough. For example, it could easily be pointed out that the results of the National Breast Cancer Screening Study sit comfortably within the confidence intervals of a Cochrane Collaboration overview of the screening trials, with no hint of heterogeneity2. If anything, the trial in that overview that is closest to being an outlier is the Swedish two-county trial, whose authors are the shrillest of all the critics3.
The debate is so polarized that, leaving aside possible conflicts of interest, the only assumption that can be made is that the clash is one of ideology rather than scientific discourse. In other words, the true believers in the screening dogma will never be persuaded of the error of their ways by data alone, and so when facts don’t fit their prejudice, they resort to ad hominem attacks.
I was one of those who established the first screening centre in London and South East England in 1988, but as an open-minded clinical scientist, I allowed the emerging new data to change my mind. With all due modesty, that is what is called an expression of scientific integrity. Of course, as Narod points out, the prolonged and futile debate merely inhibits real progress on the subject. The importance of breast screening programs lies not in their success, but in their failure. As Huxley put it, “The tragedy of science is the slaying of a beautiful hypothesis by an ugly fact.”
The national breast screening programs around the world have provided us with a natural experiment of the greatest historical importance, not because of their success in reducing breast cancer mortality, but because of the observations that have emerged concerning overdiagnosis of the disease4,5. About two hundred years ago, cancer was defined by its microscopic appearance. With the discovery and use of the modern microscope, the nineteenth century saw the birth of scientific oncology. Rudolf Virchow, often called the founder of cellular pathology, provided the scientific basis for the modern pathologic study of cancer6. As earlier generations had correlated autopsy findings observed with the unaided eye with the clinical course of cancer one hundred years earlier7, so Virchow correlated the microscopic pathology of the disease. However, the material he was studying came from the autopsies of patients dying from cancer. In the mid-nineteenth century, pathology correlations were performed either on cadavers or on living subjects presenting with locally advanced or metastatic disease who were almost always predetermined to die in the absence of effective therapy. Since then, and without pause for thought, the microscopic identification of cancer according to those classical criteria has been associated with the assumed prognosis of fatal disease in the absence of treatment.
A syllogism at the heart of the diagnosis of cancer therefore runs like this: People frequently die from malignant disease. Under the microscope, this malignant disease has many histologic features that we will call “cancer.” Ergo, anything that looks like “cancer” under the microscope will kill you. The screening debacle therefore suggests that some of the earliest stages of “cancer,” if left unperturbed, will not progress to a disease with lethal potential. Those pathologic entities might have microscopic similarity to true cancers, but their appearances alone are insufficient to predict a life-threatening disease.
Conventional mathematical models of cancer growth are linear or logarithmic—in other words, completely predictable at the outset. They predict transition from in situ phases to early invasive, and from early invasive to late invasive over time. Most natural biologic mechanisms are nonlinear or are better described by chaos theory8. Prolonged latency followed by catastrophe should not be all that surprising. We accept the case for prostate cancer, because we know that most elderly men will die with prostate cancer in situ and not of prostate cancer. In fact, the United Kingdom’s national prostate-specific antigen screening trial (protect) is predicated on that fact, with two a priori outcome measures defined: deaths from prostate cancer, and the number of cancers over-detected and treated unnecessarily9.
Next, it is worth noting that, contrary to all common-sense predictions, the increased detection rate of ductal carcinoma in situ has led to an increase in the mastectomy rate for the screened population4,5. Up to 45% of women with a screen-detected case of ductal carcinoma in situ end up undergoing mastectomy because of the multicentricity of the disease10. And yet the paradox is that clinically detected multicentric invasive breast cancer is relatively uncommon11. Surely that is proof enough that at least half the foci of ductal carcinoma in situ will regress if left alone; of course, determining which half remains the problem.
In conclusion, then, it can be stated with a great deal of conviction that a large proportion (on the order of 50%) of screen-detected (preclinical) foci of breast cancer are not programmed to progress if left unperturbed. That observation is of seismic importance and could set the agenda for breast cancer research into the next decade. The choice to ignore those observations, either because they do not support personal prejudice or because of some sleazy political agenda, will result in our community missing an opportunity of a life-time—and that would be unforgivable.
Narod is to be congratulated for his systematic and robust rebuttal of the unjustified attempts to destroy the credibility of the Canadian trial by a small group of vociferous critics who provide a background noise so loud that it nearly drowns out the true signal of the 25-year experiment of population screening for breast cancer.
“There’s non so blind as those that will not see.”— Jonathan Swift, Polite Conversation
Curr Oncol. Oct 2014; 21: 205–207. Screening mammography: the turning of the tide? W.D. Foulkes, MBBS PhD McGill University, Montreal, Quebec This issue of Current Oncology features a Counter-currents article by Dr. Steven Narod, “Reflections on screening mammography and the early detection of breast cancer”1, that is accompanied by a commentary from Professor Michael Baum2 supporting Narod’s thesis. Indeed, in Baum’s view, Narod’s only error was not to push home the point that the Canadian National Breast Cancer Screening Study (nbss) is not an outlier among mammography screening studies. He commends Narod for a measured response to the widespread criticism that followed publication of the 25-year follow-up results of the by now notorious nbss.
It seems as if almost everyone has an opinion on screening mammography. Everyone is entitled to an opinion, of course; but discussions about mammographic screening tend to take on a special, almost unique, quality—which perhaps speaks to the investments (financial, psychological, and career) made by many of the protagonists, which Professor Baum fleetingly mentions as potential conflicts of interest in his editorial. Baum prefers to see the ongoing debate—if that is what it is—as a clash of ideologies. But what are these ideologies that are so opposed?
Essentially, Baum’s argument is that the proponents of screening are not really scientists, in the sense that they do not accept refutation of data by data. He could be right, but I think the more parsimonious and psychologically more plausible explanation is that the aforementioned investments are simply too great: the stakes are too high. That the stakes are high is, in my view, very clear. Breast cancer is a common disease, and if population-based screening mammography is shown to have failed and is therefore no longer offered, billions of dollars would be saved every year in the United States alone3.
Narod contrasts the results of two large trials of mammography (one carried out in Sweden, the two-county study) with the nbss data. Having read these carefully laid out arguments, I think that most disinterested, but informed, readers will accept that many of the legion of criticisms that have been placed at the door of the nbss simply do not hold up to scrutiny. But mud sticks, and so many observers who do not like the results of the nbss point again and again to the same “flaws.”
One of Narod’s most telling points is that the survival curves for the two arms of the Swedish trial continue to remain separate up to 29 years after the trial was started. That observation is not consistent with any known effect of mammographic screening. It is much more likely that the populations were simply different to start with.
Further discussion of the pros and cons of these two trials is now fairly pointless. There are not much new data to be had, and I can’t see Drs. Kopans and Tabár, on reading Narod’s article, deciding that perhaps the benefits of mammography have, after all, been overestimated. Without new data, we can’t resolve this critical issue. So perhaps we need to stop the current process and actually do some new research to gather the required data.
A recent Perspective article in the New England Journal of Medicine4 noted the presence of a deep chasm separating women’s views of the likely benefit of mammographic screening and the actual data available. The nongovernmental Swiss Medical Board subsequently determined that women could not make informed decisions about screening without access to more nuanced information. Moreover, the Board felt that the benefits of mammographic screening were likely to be so small that no new screening programs should be introduced and existing programs should be allowed to run down. Their decision caused the expected uproar, but it is interesting to note that the results of a reader poll after a Clinical Decisions article 2 years earlier in the New England Journal of Medicine5 showed that a clear majority did not think that screening mammography should be started at age 40. Those results are contrary to the recommendation of many breast cancer organizations. But on the basis of these newer findings, it seems to me that the tide has turned, insofar as there are now enough interested parties prepared to question the benefits of mammography.
One of the points that Narod makes bears some discussion: He sees the problem not in terms of 30-year-old mammography machines in nbss study, but in 30-year-old thinking about the biology of breast cancer on the part of those who support screening. Logically, it can be seen that, as breast cancers enlarge, the number of cancer cells within them increases, which can provide opportunities for more malignant clones to emerge. Earlier detection will thus prevent those emerging clones from worsening outcomes. This quasi-Halstedian view, that a breast cancer makes a stately progression through biologically distinct and distinguishable stages and that the grade worsens as the tumour enlarges (assumptions that are at the heart of the original explanation of how mammography “works”6), are no longer part of mainstream thinking about breast cancer biology. Even ductal carcinoma in situ seems to possess many of the molecular changes found in invasive breast cancers, albeit at lower frequencies7,8. It seems as if the “die is cast” fairly early in the life of a breast cancer9. Intrinsic subtypes hold true as cancers grow and metastasize10, and the sojourn time varies from subtype to subtype11. Some breast cancers regress12. Others grow very rapidly13. These are not ideal biologic circumstances for the success of an “across the board” screening program. That conclusion is even borne out by a careful examination of the two-county study data14. The one group for whom screening mammography would be hoped to work—women between 40 and 49 years of age with a grade iii breast cancer (a group likely to contribute disproportionately to the observed mortality from breast cancer)—does not seem to achieve any mortality savings (see Figure 20 in Tabár et al.14). Survival at 16 years from randomization was identical in the invited and screened groups (relative risk: 0.95; 95% confidence interval: 0.55 to 1.64). One wonders if, in fact, the shoe is on the other foot. What has been learned about interpreting screening data from the current understanding of the natural history of breast cancer?
On the other side of the ledger, overdiagnosis has emerged in the past several years as a major issue in breast cancer screening. Quantifying the benefits and harms of mammography make for sobering reading by disinterested parties. If one starts with a sample of 1000 U.S. women 50 years of age, and if those women are screened annually for a decade, fewer than 4 women will avoid a breast cancer death; 3–14 women will suffer the consequences of over-diagnosis; and many hundreds will have at least 1 false alarm15. Work by Welch and Frankel suggests that women would think differently about mammographic screening for breast cancer if they were made aware of those figures at time of invitation for screening. Using best estimates, only 1 woman in 4 who develop a screen-detected breast cancer will avoid a breast cancer death16. The other 3 will do just as well, or just as poorly, without screening—or, of more concern, will have been diagnosed with a cancer that was not destined to ever present clinically. In the observational Norwegian study, only one third of the reduction in deaths from breast cancer could be attributed to mammographic screening per se17. Most women with a screen-detected breast cancer are therefore either diagnosed early (but with no effect on outcome) or are overdiagnosed.
We have been here before. Maureen Roberts, director of the Edinburgh breast screening project, died of breast cancer in 1989. While hopeful that mammographic screening would benefit women, she concluded from an analysis of the Edinburgh trial results that it did not. Before she died, she wrote “Breast screening: time for a rethink?” for the British Medical Journal18, concluding, “I feel sad to be writing this; sad because naturally after so many years I am sorry that breast screening may not be of benefit. I am also sad to seem to be critical of the many dear and valued colleagues I’ve worked with over the years, particularly those who have made such a magnificent contribution to the care and welfare of women with breast cancer. But they will recognise that I am telling the truth.”
It is time to work toward a trial of screening mammography that will incorporate variable thresholds, molecular markers, genetic testing, and psychological and physical measures of the effect of overdiagnosis. One of the two authors of the New England Journal of Medicine Perspective article discussed earlier, an ethics representative on the Swiss Medical Board, has argued that there is a moral requirement for a randomized controlled trial of mammography19 based on Welch’s idea of differing detection thresholds. I believe that women will be interested in such a study. But because almost every major U.S. medical organization focusing on breast cancer prevention, diagnosis, or treatment has stated that women should begin undergoing mammography annually from the age of 40 years, will any agency have the courage to fund it?
1. Mammograms May Offer Less Benefit Than You Think:
In one survey, most women said they believed mammography reduced the risk of breast cancer deaths by at least half and prevented at least 80 deaths per 1,000 women screened.5 In reality, mammography may, at best, offer a relative risk reduction of 20 percent and prevent in absolute terms only onebreast-cancer death per 10,000 women.
2. Mammography May Increase the Risk of Breast Cancer in Women with a BRCA 1/2 Mutation:
Results published in the British Medical Journal (BMJ) show that women carrying a specific gene mutation called BRCA1/2 (which is linked to breast cancer) are particularly vulnerable to radiation-induced cancer.6
Women carrying this mutation who were exposed to diagnostic radiation (which includes mammograms) before the age of 30 were twice as likely to develop breast cancer, compared to those who did not have the mutated gene. They also found that the radiation-induced cancer was dose-responsive, meaning the greater the dose, the higher the risk of cancer developing.
3. False Positives are Common (and Dangerous)
In the US, the risk of having a false-positive test over 10 mammograms is a concerning 58 percent to 77 percent!7, 8 When a woman is told she may have breast cancer, it causes considerable anxiety and psychological distress. Meanwhile, you will be subjected to more testing, such as biopsy or surgery, which carry their own set of risks, unnecessarily.
4. Mammograms May Not Work if You Have Dense Breasts
Up to 50 percent of women have dense breast tissue, which makes mammograms very difficult to decipher. Dense breast tissue and cancer both appear white on an X-ray, making it nearly impossible for a radiologist to detect cancer in these women. It’s like trying to find a snowflake in a blizzard.
Breast density laws have been passed in California, Connecticut, New York, Virginia, and Texas, making it mandatory for radiologists to inform their patients who have dense breast tissue that mammograms are basically useless for them. A law is now being considered at a federal level as well.
5. There are Other Screening Options
There are other screening options, each with their own strengths and weaknesses, and you have a right to utilize those options. Remember, only a biopsy can confirm cancer. Screening tools only aid in the process of showing concern.
Your Waist Size Is Linked to Your Breast Cancer Risk It’s important to remember that getting a mammogram, if you choose to, is not the same as prevention. In order to truly avoid breast cancer, you need to focus your attention on actual prevention and not just early detection, and one way to do this is by maintaining a healthy weight, and, particularly, a healthy waist size.
Researchers analyzed data from 93,000 mostly overweight post-menopausal women. This included data such as their general health, cancer status, and skirt size (which was used as a gauge of waist size). The latter – skirt size – was strongly linked to breast cancer risk.9 As TIME reported:10
“An increase in skirt size was the single most predictive measure of breast cancer risk, the study concluded. When women went up a single skirt size over a 10-year span between their mid-20s and mid-60s, they were shown to have a 33% greater risk of developing breast cancer after menopause. Buying two skirt sizes up during that same period was linked to a 77% increased risk.”
Clothing sizes can be quite ambiguous, of course, with a size 8 in one brand equal to another’s size 10. Yet, the premise that increasing waist size might increase cancer risk is sound. Breast cancer is the most common cancer in women, and obese women are thought to be up to 60 percent more likely to develop cancer than those of normal weight.
The reason for this increased risk is because many breast cancers are fueled by estrogen, a hormone produced in your fat tissue. So the more body fat you have, the more estrogen you’re likely to produce. However, excess fat around your mid-section may be particularly dangerous.
Why Your Waist-to-Hip Ratio Matters If you have a high waist-to-hip ratio, i.e. you carry more fat around your waist than on your hips, you may be at an increased risk for certain chronic conditions. Certain body compositions do tend to increase your risk of chronic disease, and carrying extra inches around your midsection has been repeatedly shown to increase cardiovascular health risks. Your waist size is also a powerful indicator of insulin sensitivity, as studies clearly show that measuring your waist size is one of the most powerful ways to predict your risk for diabetes, and this could also play a role in cancer as well.
To calculate your waist-to-hip ratio, measure the circumference of your hips at the widest part, across your buttocks, and your waist at the smallest circumference of your natural waist, just above your belly button. Then divide your waist measurement by your hip measurement to get the ratio. (The University of Maryland offers an online waist-to-hip ratio calculator11 you can use.) To determine your waist-to-hip ratio, get a tape measure and record your waist and hip circumference. Then divide your waist circumference by your hip circumference. For a more thorough demonstration, please review the video below.
|Waist to Hip Ratio||Men||Women|
|Moderate Risk||0.96-0.99||>0.81 – 0.84|
The Sugar Connection Obesity, including abdominal obesity, is driving up rates of breast cancer in many developed countries. And what is driving up rates of obesity? Many factors, actually, but sugar certainly plays a primary role. There is no shortage of research linking excessive sugar consumption with obesity, and the intake of sugar-sweetened beverages appears to have a particularly strong link. It was more than five years ago when UCLA researchers found that adults who drank at least one sugar-sweetened beverage a day are 27 percent more likely to be overweight or obese.12 Even those who only drank soda occasionally had a 15 percent greater risk.
This is far more than simply an issue of consuming “empty calories,” as sugary drinks, soda, and even fresh-squeezed fruit juice contain fructose, which has been identified as one of the primary culprits in the meteoric rise of obesity and related health problems—in large part due to its ability to turn on your “fat switch.” Alarmingly, research presented at the American Heart Association’s Epidemiology and Prevention/Nutrition, Physical Activity and Metabolism 2013 Scientific Sessions suggested sugary beverages are to blame for about 183,000 deaths worldwide each year, including 133,000 diabetes deaths, 44,000 heart disease deaths, and 6,000 cancer deaths.
About 77 percent of food items in US grocery stores contain added sugar. So it’s no wonder that, while the American Heart Association recommends a daily sugar limit of six teaspoons for women and nine for men, the average American consumes more like 22. If health agencies really wanted to make a dent in breast cancer, they would focus on sharing the truth about sugar (and grains), and their role in obesity and cancer. Unfortunately, breast cancer is big business, and mammography is one of its primary profit centers. This is why the industry is fighting tooth and nail to keep it, even if it means ignoring (or downplaying) the truth.
Avoiding Sugar and Other Top Breast Cancer Prevention Tips I believe the vast majority of all cancers, including breast cancer, could be prevented by strictly applying basic, commonsense healthy lifestyle strategies, such as the ones below. No available screening method, whether mammography or otherwise, is going to lower your risk of breast cancer… but the tips that follow will:
- Avoid sugar, especially fructose, and processed foods. All forms of sugar are detrimental to your health in general and tend to promote cancer. Refined fructose, however, is clearly one of the most harmful and should be avoided as much as possible. This automatically means avoiding processed foods, as most are loaded with fructose.
- Optimize your vitamin D levels. Vitamin D influences virtually every cell in your body and is one of nature’s most potent cancer fighters. Vitamin D is actually able to enter cancer cells and trigger apoptosis (programmed cell death). If you have cancer, your vitamin D level should probably be between 70 and 100 ng/ml. Vitamin D works synergistically with every cancer treatment I’m aware of, with no adverse effects. Ideally, your levels should reach this point by exposure to the sun or a tanning bed, with oral vitamin D used as a last resort and balanced by other nutrients like vitamin K2 and magnesium.
- Limit your protein. Newer research has emphasized the importance of the mTOR pathways. When these are active cancer growth is accelerated. One way to quiet this pathway is by limiting your protein to one gram of protein per kilogram of lean body mass, or roughly a bit less than half a gram of protein per every pound of lean body weight. For most people, this ranges between 40 and 70 grams of protein a day, which is typically about 2/3 to half of what they are currently eating. You can eat 25% more if you are exercising or pregnant.
- Avoid unfermented soy products. Unfermented soy is high in plant estrogens, or phytoestrogens, also known as isoflavones. In some studies, soy appears to work in concert with human estrogen to increase breast cell proliferation, which increases the chances for mutations and drives the phenotype associated with cancer.
- Improve your insulin and leptin receptor sensitivity. The best way to do this is by avoiding sugar and grains and restricting carbs to mostly fiber vegetables. Also make sure you are exercising, especially with Peak Fitness.
- Exercise regularly. One of the primary reasons exercise works to lower your cancer risk is because it drives your insulin levels down, and controlling your insulin levels is one of the most powerful ways to reduce your cancer risks. It’s also been suggested that apoptosis (programmed cell death) is triggered by exercise, causing cancer cells to die in the way nature intended. Studies have also found that the number of tumors decrease along with body fat, which may be an additional factor. This is because exercise helps lower your estrogen levels, which explains why exercise appears to be particularly potent against breast cancer.
In addition to exercise, try to limit your sitting time to three hours a day while taking 10,000 daily steps during your non-exercise hours.
- Maintain a healthy body weight. This will come naturally when you begin eating right and exercising. It’s important to lose excess body fat because fat produces estrogen, creating a vicious self-perpetuating cycle.
- Drink a pint to a quart of organic green vegetable juice daily. This is a simple way to get more cancer-fighting nutrients into your diet. Please review my juicing instructions for more detailed information.
- Get plenty of high-quality, animal-based omega-3 fats, such as krill oil. Omega-3 deficiency is a common underlying factor for cancer.
- Curcumin. This is the main active ingredient in turmeric and in high concentrations can be very useful adjunct in the treatment of cancer. It actually has the most evidence-based literature supporting its use against cancer of any nutrient, including vitamin D.13 For example, it has demonstrated major therapeutic potential in preventing breast cancer metastasis.14 It’s important to know that curcumin is generally not absorbed that well, so I’ve provided several absorption tips here. Newer preparations have also started to emerge, offering better absorption. For best results, you’ll want to use a sustained-release preparation.
- Avoid drinking alcohol, or at least limit your alcoholic drinks to one per day.
- Avoid electromagnetic fields as much as possible. Even electric blankets may increase your cancer risk.
- Avoid synthetic hormone replacement therapy, especially if you have risk factors for breast cancer. Many forms of breast cancer are estrogen-fueled, and according to a study published in the Journal of the National Cancer Institute, breast cancer rates for women dropped in tandem with decreased use of hormone replacement therapy. (There are similar risks for younger women who use oral contraceptives. Birth control pills, which are also comprised of synthetic hormones, have been linked to cervical and breast cancers.) If you are experiencing excessive menopausal symptoms, you may want to consider bioidentical hormone replacement therapy instead, which uses hormones that are molecularly identical to the ones your body produces and do not wreak havoc on your system. This is a much safer alternative.
- Avoid BPA, phthalates, and other xenoestrogens. These are estrogen-like compounds that have been linked to increased breast cancer risk.
- Make sure you’re not iodine deficient, as there’s compelling evidence linking iodine deficiency with certain forms of cancer. Dr. David Brownstein, author of the book Iodine: Why You Need It, Why You Can’t Live Without It, is a proponent of iodine for breast cancer. It actually has potent anticancer properties and has been shown to cause cell death in breast and thyroid cancer cells. For more information, I recommend reading Dr. Brownstein’s book. I have been researching iodine for some time ever since I interviewed Dr. Brownstein, as I do believe that the bulk of what he states is spot on. However, I am not at all convinced that his dosage recommendations are correct. I believe they are far too high.
- Avoid charring your meats. Charcoal or flame-broiled meat is linked with increased breast cancer risk. Acrylamide—a carcinogen created when starchy foods are baked, roasted, or fried—has been found to increase cancer risk as well.
Breast screening: an obsessive compulsive disorder. in Cancer Causes Control. 2014 Jul 11. Prof Yunus Luqmani a British oncology biochemist, Kuwait University writes “Mammographic screening was founded on the premises that “it saves lives”, ‘early is better than late,’ which prevails in several countries but controversial since its inception. Findings and interpretation of clinical trials data vary considerably, with disagreement on the outcome and value of such procedure, not just about the benefits but about the potential harms of mass screening. Many are being screened for the benefit of the few. Even this might be acceptable but for concern for many women with screen detected cancers that will potentially not cause them harm, and who are very likely receiving unnecessary treatment. Many call for complete cessation of indiscriminate screening if not re-assessment of age and periodicity . Of great concern is that screening is being vigorously advocated by many healthcare workers, the media, and lay persons alike without proper awareness or appreciation of the consequences. Although some National leaflets now present a truer picture, there is distinct lack of transparency to allow women to distinguish perception from reality and to make informed choices. How many would elect to be screened if they knew that for every one woman who is notionally saved by early detection, anywhere from 2 to 10 otherwise healthy women are being turned into breast cancer patients?
Benefits of mammography
|“the benefits of screening mammography are modest at best” (Elmore & Harris BMJ 2014;348:g3824). This is the conclusion after the latest research to come out of Norway where the introduction of screening has been gradually introduced over the last 2 decades (Weedon-Fekjaer et al BMJ 2014;348:g3701).The Norwegian authorities invited women between 50 and 70 years old to attend for screening every second year and looked at before and after death rates from breast cancer. They found RELATIVE risk reduction of 28% in those invited compared with those not invited to be screened. Without knowing the ACTUAL risk reduction or the harms of screening this sounds like a “good deal”. However it is an observational study not a randomised trial and therefore susceptible to various biases.For women to make up their own minds about screening, actual figures of benefits and harms need to be given because without accuracy perceived dangers and benefits are very far from reality. For example in the US or UK asking women about their estimates of breast cancer deaths – taking 1000 women aged 50 and following them for 20 years – gave the following results:
Women believe that breast cancer is a far greater threat than it really is. They also believe that screening halves such risk.
If actual death reductions from breast cancer are taken into account, screening benefits are modest at best and if all cause deaths are taken into account the benefits all but disappear.
DIET RISKS FOR BREAST CANCER:
VITAMIN INTAKE AND BREAST CANCER:
Commentary The mammography debate is one of the facets of the Miami Breast Cancer Conference this year. It seems as though the field of breast cancer has always been controversial, going back half a century, and breast cancer is a disease that, more than most others, is very polarizing. This disease engenders great passion—and great debate, which has been ongoing about the role of screening mammography.
A few weeks ago, The New York Times covered an article that was published in the British Medical Journal 1 about the Canadian National Breast Screening Study. On the surface, this study failed to show any benefit from mammography. That was the story that the writer, Gina Kolata, picked up and ran with. Ms. Kolata had written about her own experience with breast cancer a number of years ago; her breast cancer had not been picked up on a mammogram, and so she is somewhat biased.
In short, the Canadian study evaluated mammograms from more than 90,000 women who had very primitive mammograms between 1980 and 1984, and that is really the first problem with this study: the technology and the equipment then was incredibly limited, such that the mammograms only showed 30% of breast cancers; whereas, today, mammography detects 70% to 80% of breast cancers. Thus, taking results generated by technology from 34 years ago and making a conclusion about them in today’s world is a stretch.
One of the fundamental flaws of the Canadian study, besides the dated technology on which the conclusions were based, was that it was not randomized. Nurses, and, in some provinces in Canada, doctors, did a clinical breast exam, and, if they felt a mass or a lump, they preferentially put the patient into the mammography arm. That is what I would have done in their place; if I felt a lump, I would not be willing to send someone home.
By the end of the study, there were more than 100 extra breast cancers in the mammography arm and more breast cancers that had spread to lymph nodes in the mammography arm. And, in fact, the chance of dying of breast cancer was higher in the mammography arm.
All of the authorities with whom I have ever spoken or read who have reviewed this study dismiss it as very flawed. A number of the doctors who were involved with the study resigned their positions in protest. Despite all of that, The New York Times ran an article headlined, “Vast Study Casts Doubts on Value of Mammograms” (February 11, 2014).
Well, it is a vastly flawed study, and, in fact, there are six other, much larger and much better controlled studies, all of which showed a reduction in breast cancer mortality from 20% up to 40% in women who have mammograms—and that is certainly what we observe clinically.
We felt that it was important to really highlight this at the Miami Breast Cancer Conference this year. My guess is that our audience already knows this; but, what we would like to give them is the science about why the Canadian study was flawed so that they can talk to their patients and talk to their colleagues who may not be in the breast cancer field. That is really what I think our mission is for part of this year’s conference.
We think that this is dangerous information. We think that women will unnecessarily lose their lives to breast cancer if they forego mammography, which this study frankly says one should. I have a busy practice in Brooklyn, New York, and, at least once or twice a week, I see someone, without any question, whose life was saved by a mammogram.
I think that we all agree we need something better than mammography. We all agree that mammography can lead to over-diagnosis of breast cancers, and over-diagnosis happens, of course, when we screen for diseases in other areas of the body. We all accept this limitation.
But, for a major media outlet to take a single study that was deeply flawed and not even mention the existence of other studies, even as a point–counterpoint, I think was a bit outrageous!
12 March 2014 this publication on the Huffington Post website today under screening mammography is as appropriate as when it was published in 2010:
BREAST CANCER UNAWARENESS MONTH: Rethinking Mammograms
The NBCAM has assured women that “early (mammography) detection results in a cure nearly 100 percent of the time.” More specifically, the NBCAM is directed to claims for reducing the incidence and mortality of breast cancer through early detection by annual mammography starting at age 40. Moreover, mammograms can miss cancers in premenopausal women due to the density of their breasts, and also fail to detect cancers smaller than half an inch.
Still denied by the ACS is clear evidence that premenopausal mammography poses significant risks of breast cancer. The routine practice of taking two films annually for each breast results in approximately 0.5 rad (radiation absorbed dose) exposure. This is about 500 times the dose from a single chest X-ray and is broadly focused on the entire chest rather than narrowly on the breast. This is also 25 times higher than is allowed by the Environmental Protection Agency for whole-body radiation from local nuclear industries (0.02 rad). Moreover, the breast is the most sensitive organ to ionizing radiation.
As warned by the prestigious National Academy of Sciences in 1972 but still ignored by the ACS, the premenopausal breast is highly sensitive to the risks of cancer from mammography, as each rad exposure increases the risks of breast cancer by 1 percent. This results in a cumulative 10 percent increased risk for each breast following a decade of routine screening. This can also accounts for the 19-percent increased incidence of breast cancer since 1975. Not surprisingly, the prestigious U.S. Preventive Task Force, supported by the National Breast Cancer Coalition, warned last year against routine premenopausal mammography. Also, not surprisingly, routine premenopausal mammography is practiced by no nation other than the U.S.
Risks of premenopausal mammography are some four-fold greater for the 2 percent of women who are carriers of the A-T gene (ataxia telangiectasia) and are highly sensitive to the carcinogenic effects of radiation. By some estimates, this accounts for up to 20 percent of all breast cancers diagnosed annually. Compounding these problems, missed cancers are common in premenopausal women due to the density of their breasts.
That most breast cancers are first recognized by women was admitted by the ACS in 1985. “We must keep in mind that at least 90 percent of the women who develop breast cancer discover the tumors themselves.” Furthermore, an analysis of several 1993 studies showed that women who regularly performed breast self-examination (BSE) detected their cancers much earlier than women failing to examine themselves. The effectiveness of BSE, however, depends on training by skilled professionals, enhanced by an annual clinical breast examination. Nevertheless, in spite of such evidence, the ACS dismisses BSE, and claims that “no studies have clearly shown [its] benefit.”
As reported in our 1999 publication in the International Journal of Health Services, an article in a leading Massachusetts newspaper featured a photograph of two women in their twenties. The article promised that early detection by mammography results in a cure “nearly 100 percent of the time.” Questioned by journalist Kate Dempsey, an ACS communications director responded: “The ad isn’t based on a study. When you make an advertisement, you just say what you can to get women in the door. You exaggerate a point — Mammography today is a lucrative [and] highly competitive business.”
If all 20 million U.S. premenopausal women submitted to annual mammograms, the minimal annual costs would be $2.5 billion. Such costs would be increased some fourfold if the industry, supported by radiologists, succeeds in its efforts to replace film machines, costing about $100,000, with high-tech digital machines, costing over $400,000, even in the absence of any evidence for their improved effectiveness.
With this background, it is hardly surprising that the National Breast Cancer Awareness Month neglects to inform women how they can reduce their risks of breast cancer. In fact, we know a great deal about its avoidable causes which remain ignored by the ACS. These include:
- Prolonged use of the Pill, and estrogen replacement therapy.
- Prolonged consumption of milk from cows injected with a genetically engineered growth hormone to increase milk production. This milk is contaminated with high levels of a natural growth factor, which increases risks of breast cancer by up to seven-fold.
- High consumption of meat, as it is contaminated with potent natural or synthetic estrogens. These are routinely implanted in cattle before entry into feedlots, about 100 days prior to slaughter, to increase muscle mass and profits for the meat industry.
- Prolonged exposure to a wide range of hormonal ingredients in conventional cosmetics and personal care products.
- Living near hazardous waste sites, petrochemical plants, power lines, and nuclear plants.
The enthusiastic and continuing support of premenopausal mammography by the ACS is hardly surprising in view of its major conflicts of interest that still remain unrecognized. Five radiologists have served as ACS presidents. In its every move, the ACS promotes the interests of the major manufacturers of mammogram machines and films, including Siemens, DuPont, General Electric, Eastman Kodak and Piker. The mammography industry also conducts research for the ACS, serves on its advisory boards, and donates considerable funds. DuPont is also a substantial backer of the ACS Breast Health Awareness Program. It sponsors television shows touting mammography; produces advertising, promotional materials and literature for hospitals and doctor; and lobbies Congress for legislation promoting the availability of mammography. The ACS has been and remains strongly linked with the mammography industry, while ignoring or criticizing the value of breast self-examination, even following training by a qualified nurse or clinician.
The ACS conflicts of interest extend well beyond the mammography industry. The ACS has received contributions in excess of $100,000 from a wide range of “Excalibur (industry) Donors,” who manufacture carcinogenic products. These include petrochemical companies (DuPont, BP and Pennzoil), Big Pharma (AstraZenceca, Bristol Myers Squibb, GlaxoSmithKline, Merck & Company and Novartis), and cosmetic companies (Christian Dior, Avon, Revlon and Elizabeth Arden).
Samuel S. Epstein, M.D. is professor emeritus of Environmental and Occupational Medicine at the University of Illinois at Chicago School of Public Health; Chairman of the Cancer Prevention Coalition; and a former President of the Rachel Carson Trust. His awards include the 1998 Right Livelihood Award and the 2005 Albert Schweitzer Golden Grand Medal for International Contributions to Cancer Prevention. Dr. Epstein has authored 270 scientific articles and 20 books on cancer prevention, including the groundbreaking “The Politics of Cancer” (1979), and most recently “Toxic Beauty” (2009, Benbella Books: http://www.benbellabooks.com) about carcinogens, besides other toxic ingredients, in cosmetics and personal care products. Email: email@example.com. Web: http://www.preventcancer.com.
update 6 March 2014 Switzerland debates dismantling its breast cancer screening programme BMJ 2014;348:g1625 “A row has erupted in Switzerland after the Swiss Medical Board recommended that the country’s mammography screening programme for breast cancer be suspended because it leads to too many unnecessary interventions.
In a report made public on 2 February, the board said that while systematic mammography screening for breast cancer saved 1-2 women’s lives for every 1000 screened, it led to unnecessary investigations and treatment for around 100 women in every 1000.1 “The desirable effect is offset by the undesirable effects,” said the report, which was based on study data from 1963 to 1991 comparing 1000 women who were screened with 1000 women who were not. The report also concluded that screening was not cost effective.…”
update 1 Mar 2014 Supporting informed decision making when clinical evidence and conventional wisdom, clash. The nub of the screening mammography war – and all hard-sell marketing hype- is elegantly analyzed by a USA multiUniversity Communications team in Against conventional wisdom: when the public, the media, and medical practice collide. Jakob Jensen ea argue that “the screening mammography controversy was driven by the systematic removal of uncertainty from science communication. To increase comprehension and adherence, health information communicators remove caveats, limitations, and hedging so science appears simple and more certain. This streamlining process is, in many instances, initiated by researchers as they engage in dissemination of their findings, and is facilitated by public relations professionals, journalists, public health practitioners, and others whose tasks involve using the results from research for specific purposes. Uncertainty is removed from public communication because many communicators believe that it is difficult for people to process and/or that it is something the audience wants to avoid. Uncertainty management theory posits that people can find meaning and value in uncertainty. CONCLUSIONS: Science is routinely simplified as it is prepared for public consumption. In line with the model of information overload, this practice may increase short-term adherence to recommendations at the expense of long-term message consistency and trust in science”.
We see the same collusion between corporate marketeers and government regulators in so many high-profit industries:
* on Pubmed, screening mammography features for 50 years, and continued to expand exponentially without hindrance until enough epidemiologists – led by the Cochrane Group- collectively rang enough alarm bells the past decade. The zealous huge-profit USA radiology-oncology industry simply shouted down the negative result of the massive Canadian Screening Mammography trial outcome 30 years ago in 90 000 women, and continue to do so with the 25year results now reported. The huge Breast Industry retaliates by threatening whistle blowers.
*and as a result, the past 30years,- against all rational food science and biology – Montsanto’s Government- approved rape of healthy food agriculture by genetically modified crops laced with toxic environmentally persistent glyphosate C3H8NO5P- Roundup.
It is no irony that one of the leading medical scientists of the 20th century Dr John Gofman took part in the Manhattan nuclear Project, was a pioneer of VLDL lipidology, and then an activist for protecting women against the accumulating harm of mammography – “there is no safe dose of radiation”.
|at Exam.||Resulting Risk of Mammogram-Induced Breast Cancer. 1998|
|Any age in||1 exam:||1 chance in about 1,100.|
|30-34 range.||5 exams:||5 chances/1100, or 1 chance in 220.|
|Any age in||1 exam:||1 chance in about 1,900.|
|35-49 range.||10 exams:||10 chances/1900, or 1 chance in 190.|
|Any age in||1 exam:||1 chance in about 2,000.|
|50-64 range.||15 exams:||15 chances/2,000, or 1 chance in 133.|
Dr Emily Transue MD eloquently describes her personal disillusionment with screening mammography.
They fail to list other adverse effects: 7. Pain and bruising of crush mammography- sometimes prolonged; 8. spreading early and likely dormant cancer. 9. Increased incidence of breast cancer and thus more irradiation, mastectomy and all-cause mortality, and 10. complications of surgery, radiotherapy and chemotherapy. ………………………..
The Canadian study, launched in 1980, is the only trial to enroll participants in the modern era of routine adjuvant systemic treatment for breast cancer, and the women were educated in physical breast examination as advocated today.4 These important features may make this study more informative for a modern setting, compared with other randomised trials. The results of the study are strikingly similar—for both lack of efficacy and extent of overdiagnosis—to recent studies evaluating today’s screening programmes.5 6 7 The real amount of overdiagnosis in current screening programmes might be even higher than that reported in the Canadian study,4 because ductal carcinoma in situ, which accounts for one in four breast cancers detected in screening programmes,8 was not included in the analyses.
Other studies also indicate that improved treatment rather than screening is the reason for the decline in breast cancer mortality during the past four or five years.5 7 Even though different studies arrive at different reductions in breast cancer mortality (from 10% to 25%), these benefits translate to only marginal differences in absolute effects. Much larger variation is seen in the estimates of overdiagnosis.6 In studies based on statistical modelling, overdiagnosis was less than 5%.6 By contrast, most observational studies report higher estimates of overdiagnosis, ranging from 22% to 54%,6 depending on denominator used.9 When the number of breast cancers detected at screening is used as the denominator (as in the Canadian study), the amount of overdiagnosis observed in the previous randomised controlled trials is strikingly similar (22-24%).4 10
How do the data on mammography screening compare with data on prostate cancer screening by prostate specific antigen, which is currently not encouraged in the United Kingdom and other countries owing to its small effect on mortality and large risk of overdiagnosis (www.screening.nhs.uk/prostatecancer)? The figure on bmj.com shows that the absolute harms (overdiagnosis) and benefits (mortality reduction) are not very different between the screening types. The 20 year risk of breast cancer for a 50 year old woman is 6.1% with screening (including 22% overdiagnosis 4),11 and 5.0% without screening; and the corresponding numbers for prostate cancer in a 50 year old man are 3.9% with screening (including 45% overdiagnosis 12) and 2.7% without screening.11 The 20 year risk of death from cancer for a 55 year old woman is 1.5% with screening (assuming a 20% reduction in mortality2)11 and 1.9% without screening; and the corresponding numbers for prostate cancer in a 55 year old man are 1.0% with (assuming a 20% reduction in mortality12) and 1.3% without screening.11
Nevertheless, the UK National Screening Committee does recommend mammography screening for breast cancer but not prostate specific antigen screening for prostate cancer, stating that the “aim is to only implement programs that do more good than harm and that the informed choice is a guided principle of screening” (www.screening.nhs.uk/screening). Because the scientific rationale to recommend screening or not does not differ noticeably between breast and prostate cancer, political pressure and beliefs might have a role.
We agree with Miller and colleagues that “the rationale for screening by mammography be urgently reassessed by policy makers.” As time goes by we do indeed need more efficient mechanisms to reconsider priorities and recommendations for mammography screening and other medical interventions. This is not an easy task, because governments, research funders, scientists, and medical practitioners may have vested interests in continuing activities that are well established.
RESPONSES: 12 February 2014 BMJ 2014;348:g366 : 1. rebuttal by USA radiologists : Daniel B. Kopans, Professor of Radiology Harvard Medical School. Having been one of the experts called on in 1990 to review the quality of their mammograms I can personally attest to the fact that the quality was poor (1). To save money they used second hand mammography machines. The images were compromised by scatter since they did not employ grids for much of the trial. They failed to fully position the breasts in the machines so that cancers were missed because the technologists were not taught proper positioning, and their radiologists had no specific training in mammographic interpretation.
The CNBSS’s own reference physicist wrote:“..in my work as reference physicist to the NBSS, [I] identified many concerns regarding the quality of mammography carried out in some of the NBSS screening centers. That quality [in the NBSS] was far below state of the art, even for that time (early 1980’s). ” (2)
In this latest paper (3) the authors gloss over the fact that only 32% of the cancers were detected by mammography alone. This extremely low number is consistent with the poor quality of the mammography. At least two thirds of the cancers should be detected by mammography alone (4). In their accompanying editorial (5) Kalager and Adami admit that ” The lack of mortality benefit is also biologically plausible because the mean tumour size was 19 mm in the screening group and 21 mm in the control group….a 2 mm difference.” Poor quality mammography does not find breast cancers at a smaller size and earlier stage and would not be expected to reduce deaths.
The documented poor quality of the CNBSS mammography is sufficient to explain their results and all of the above disqualifies the CNBSS as a scientific study of mammography screening, but it was even worse than that. In order to be valid, randomized, controlled trials (RCT) require that assignment of the women to the screening group or the unscreened control group is totally random. A fundamental rule for an RCT is that nothing can be known about the participants until they have been randomly assigned so that there is no risk of compromising the random allocation. Furthermore, a system needs to be employed so that the assignment is truly random and cannot be compromised. The CNBSS violated these fundamental rules (6). Every woman first had a clinical breast examination by a trained nurse (or doctor) so that they knew the women who had breast lumps, many of which were cancers, and they knew the women who had large lymph nodes in their axillae indicating advanced cancer. Before assigning the women to be in the group offered screening or the control women they knew who had large incurable cancers. This was a major violation, but it went beyond that. Instead of a random system of assigning the women they used open lists. The study coordinators who were supposed to randomly assign the volunteers, probably with good, but misguided, intentions, could simply skip a line to be certain that the women with lumps and even advanced cancers got assigned to the screening arm to be sure they would get a mammogram. It is indisputable that this happened since there was a statistically significant excess of women with advanced breast cancers who were assigned to the screening arm compared to those assigned to the control arm (7). This guaranteed that there would be more early deaths among the screened women than the control women and this is what occurred in the NBSS. Shifting women from the control arm to the screening arm would increase the cancers in the screening arm and reduce the cancers in the control arm which would also account for what they claim is “overdiagnosis”. The analysis of the results from the CNBSS have been suspect from the beginning. The principle investigator ignored the allocation failure in his trial and blamed the early excess of cancer deaths among screened women on his, completely unsupportable, theory that cancer cells were being squeezed into the blood leading to early deaths. This had no scientific basis and was just another example of irresponsibility in the analysis of the data from this compromised trial and he finally retracted the nonsense after making front page headlines (6).
The compromise of the CNBSS trial is indisputable. The 5 year survival from breast cancer among women ages 40-49 in Canada in the 1980’s was only 75%, yet the control women in the CNBSS, who were supposed to represent the Canadian population at the time, had a greater than 90% five year survival. This could only happen if cancers were shifted from the control arm to the screening arm. The CNBSS is an excellent example of how to corrupt a randomized, controlled trial. Coupling the fundamental compromise of the allocation process with the documented poor quality of the mammography should, long ago, have disqualified the CNBSS as a legitimate trial of screening mammography. Anyone who suggests that it was properly done and its results are valid and should be used to reduce access to screening either does not understand the fundamentals, or has other motives for using its corrupted results.
2. confirmation: http://www.bmj.com/content/348/bmj.g366?tab=responses Per-Henrik Zahl, MD & statistician Norwegian Institute of Public Health. In this 30-year old study, the authors report no mortality reduction when screening with mammography and 22% overdiagnosis (1). The sensitivity of the mammography technique has improved tremendously in the last three decades. Ten years ago we got digital mammography and recently we have got tomosynthesis (2). The detection rate at mammography in the Canadian study was about 3 per 1000 in the second and later screening rounds (3). In digital mammography, the corresponding detection rate is 6 per 1000 screened woman and in tomosynthesis, the detection rate is 8 per 1000 (2). It could even have been higher if the pathologists had time to perform more biopsies (personal communications). In tomosynthesis a large number of stellate lesions appear, many more than in traditional mammography, and they are probably representing a reservoir of overdiagnosed breast cancers. In the last 15 years, the rate of interval cancer has been constant and is at the same level as in Canada 30 years ago (4). Thus, the level of overdiagnosis is far much bigger today than in Canada 30 years ago.
Hence Regulators in most countries have reduced recommendations for routine screening mammography to starting at age >50yrs and stopping by 70-75years (ie 10-12 times on average through midlife); whereas Radiology Associations ignore the risks and still advise screening annually from age 40 years, for life – ie at least THREE times as many times from age 40years. So women are doubly exposed to harmful pressure both in being bullied that they need screening xray mammography – the lie that ” screening mammography saves lives” when the benefit of this is unproven, and in being forced to undergo breast crushing repeatedly. A woman who recently attended for Sure Touch in Port Elizabeth objected to having her breasts snackwiched again by compression mammography. The flippant analogy is eerie when one considers how such women are expected to attend annually to have their breasts both flattened and irradiated – and more so with cumulative frying after therapeutic radiotherapy. No wonder some end up with a hard breast. . So while the young at heart may love nudging breasts-, and massage heals, (and Bissell and Fletcher at the Berkley lab show that gentle nudging with about 50 gm pressure knocks errant breast ductal cells back into healthy behaviour) – crushing force and coersion do women harm, not good; in contrast to men where forceful digital massage may (also with putative risk) relieve the infected painful prostate.. .
update 26 May 2013 Apart from the strident promotion of preventative mastectomy by a film star, reports the past week prompt review of : why and whether aggressive breast cancer may have doubled in young women 25-39years old; and it’s prevention by natural steps.
Lisa Willis, Karen Page, Trevor Graham, Tomás Alarcón, Malcolm Alison & Ian Tomlinson from Universities of London, Oxford, Cambridge, and Barcelona this month dissect “What Can Be Learnt about Disease Progression in Breast Cancer Dormancy from Relapse Data? why Breast cancer patients have an anomalously high rate of relapse up to 25 years after apparently curative surgery removed the primary tumour. Disease progression during the intervening years between resection and relapse is poorly understood. There is evidence that the disease persists as dangerous, tiny metastases that remain at a growth restricted, clinically undetectable size until a transforming event restarts growth. This suggests a natural question and a surprising answer: why are interesting trends in long-term relapse data not more commonly observed?” But they are observed: another recent 15 year followup study, from Denmark (Grantzau ea), furthermore shows that DXRT after early breast cancer almost doubles the risk of radiotherapy-associated second cancer to 1:200 of women so treated..
These reports raise yet further doubts about the wisdom of regular mass xrayscreening of well breasts from age 50 years let alone 40years, and worse- zealous major surgery and DXRT for preclinical disease, and then even worse, ongoing xray mammographic surveillance into old age.
They point in the opposite direction: that xray screening of well breasts should be avoided; DXRT avoided in localized early breast cancer; and surveillance for breast cancer limited to the many available non-xray methods;
and that women must be encouraged instead to maintain prevention with combination of safe natural (and multisystem-protecting) means as discussed repeatedly in this column – lifestyle, diet, exercise, and massage and oral use of safe natural preventative supplements. Anticancer antiangiogenesis factors from our diet are legion, include cannabis, mushrooms, resveratrol, green tea, black rasberry and Royal jelly. One would not recommend soya against breast cancr because of its phytoestrogen potential.
Xradiation has been known for decades eg 1978 1990 to be both an angiogenic and an antiangiogenic factor in tumour growth angiogenesis (Judah Folkman 1971) . so it is obviously a double-edged sword that should certainly not be used in the witchhunt for silent and usually irrelevant precancer in well breasts.
So we have the ludicrous situation reported today in JAMA that despite all the evidence for 20 years now to stop or at least halve mass xray screening and thus (over)treatment of silent early breast cancer, “Physicians, Patients Not Following Advice From USPSTF on Mammography Screening: In 2009, the US Preventive Services Task Force (USPSTF) recommended against routine screening mammography for women under 50 years and advised biennial rather than annual screening for women aged over 49yrs. But women and physicians ignored these recommendations. A new study from Harvard found that in 2005 to 2011, the percentage of women aged 40 to 49 years reporting that they had undergone mammography screening in the previous year was the same, about 47%. As for women aged 50 to 74 years, the percentage reporting mammography screening in the previous 12 months for each year analyzed also remained essentially the same, in the upper 50% range.”
Update 21 April 2013: FIFTEEN YEAR FOLLOWUP STUDIES OF BREAST CANCER AND ALLCAUSE MORTALITY FROM MENOPAUSE ONWARDS: Overall, long-term studies do not favour invasive breast screening or adjuvant therapy of early breast cancer, but actually argue against early diagnosis and treatment of both silent breast and prostate cancer. Rather, the focus must be on safe natural prevention to reduce the occurrence of all common degenerative diseases of aging.
Erbas ea at Univ Melbourne studied all sources for the prevalence of ductal carcinoma in situ. “The reported prevalence of undiagnosed DCIS in autopsy studies, of approximately 9%, has been used to suggest a larger reservoir of DCIS may exist in the population”.
Update 18 April 2013: a new study from Italy graphically illustrates the lower sensitivity of xray screening – U/S ie ultrasound picked up ‘significantly’ more tiny asymptomatic breast cancers missed in 22,131 women with negative mammography. “The overall U/S detection was 0.185%, but 0.55% with previous cancer vs 0.145% in women without cancer history (p = 0.0004), 0.22% in dense breasts (p = 0.17) vs .156% in fatty breasts. The U/S- generated invasive assessment was 0.19% The benign to malignant open surgical biopsy ratio was thus 0.17.” This is likely more overdiagnosis unless the women simply apply the preventative measures recommended below.
But while no screening method can diagnose cancer (only invasive biopsy can), and none can guarantee there arnt cancer cells busy germinating especially if stirred up by severe anxiety, radiation, crushing, biopsy etc, Sure Touch mapping is more accurate than even U/S for reassuring while reducing referral rate for U/S.
UPDATE 14 APRIL 2013: Because of the evidence the past score years set out below that xray screening actually does more harm than good, integrative medical clinics world wide do not promote xray screening mammography. But such clinics including in Cape Town generally offer regular safe and lower-cost anatomical eg Sure Touch mechanical tactile if not ultrasound or MRI, and physiological no-touch eg thermography ie bloodflow studies, – for those who need peace of mind. Some women choose to alternate Sure Touch and thermomammography.
While only 1 in 200 women have the familial gene risk, the majority of older women have the common multiple risk factors eg longevity, estrogenic and heavy metal pollution, stress, overweight density, smoking, alcohol; and there are many simple remedies described in these columns that can reverse most of the risk factors – not just of even genetic breast cancer and increasing overweight, but of all the major diseases of aging.
The problem remains the stubbornness of third party payers including governments to listen to both the evidence and to womens’ wishes, and pay for such safe, cheaper and arguably more accurate prscreening than crush xray mammography, if any is desired or desirable .
Dr Johnnie Ham MD MSc MBA Californian ObGyn discusses why xray screening mammography and aggressive medical assault on well breasts- the witchhunt for the pot of hidden gold, silent preclinical breast cancer – is a giant con by the for-profit high-tech medical goliath industry terrorizing and mutilating naive women.
Governments -WHO silence on harms of screening mammography : What is tragicomedy is that worldwide, government Regulators seem to be standing silently firm, not saying a word about the harm likely exceeding the medical benefit- the screening and cancer industry is far too profitable in jobs, taxes and votes. Search on the internet for Government warnings on harms of screening mammography does not yield a word of warning. Regulators and Medical Schemes piously promote quality screening, but say nothing about the harms versus benefits. The FDA still promotes annual screening mammography on line without a word about the risks and harms of mammography; others like the UK NHS promote it every 2 to 3 years. Yet the US Senate is actually considering a Republican Act to promote more xray breast imaging.
UPDATE 12 April 2013 The Wiki entry on breast cancer prognosis says now: “One result of media hype- breast cancer’s high visibility -(compared to other cancers in eg men, and other common major diseases) is that statistics may be misinterpreted, such as the claim that breast cancer will be diagnosed in one in eight women during their lives—a claim that depends on the unrealistic assumption that no woman will die of any other disease before the age of 95. This obscures reality that about ten more women will die from heart disease or stroke than from breast cancer.The emphasis on breast cancer screening may be harming women by subjecting them to unnecessary radiation, biopsies, and surgery. One-third of diagnosed breast cancers might recede on their own. Screening mammography efficiently finds non-life-threatening, asymptomatic breast cancers and pre-cancers, even while overlooking serious cancers. According to Prof Gilbert Welch of Dartmouth Institute, research on screening mammography has taken the “brain-dead approach that says the best test is the one that finds the most cancers” rather than the one that finds dangerous cancers.
The latest report Lancet 2011) on the Relevance of breast cancer hormone receptors and other factors to efficacy of Tamoxifen protection after breast cancer looked at 20 trials (n=21,457) in early breast cancer . In oestrogen receptor (ER)-positive disease, about 5 years of tamoxifen halved recurrence rates throughout the first 10 years but no further gain or loss after year 10; risk was approximately independent of progesterone receptor status (or level), age, nodal status, or use of chemotherapy. Breast cancer mortality was reduced by about a third throughout the first 15 years. Overall non-breast-cancer mortality was little affected, despite small absolute increases in thromboembolic and uterine cancer mortality (both only in women older than 55 years), so all-cause mortality was substantially reduced. In ER-negative disease, tamoxifen had little or no effect on breast cancer recurrence or mortality.
This is not surprising as tamoxifen like all synthetic sex hormones /blockers has a long list of adverse effects on bone, brain, cardiovascular, bladder, mood, immunity, body weight and metabolism, womb etc.
But the Oxford UK-led (Davies ea) landmark monumental ATLAS trial (2012) from 1996 -2010 in 36 countries and 180 000 women-years (mean presentation age mid 50s, ER+ breast cancer about 1 cm size, 2/3 had mastectomy – which is now known to increase mortality) showed that after 6846 women taking tamoxifen for up to 10 years, at about 15 years from diagnosis, tamoxifen in absolute terms was only marginal benefit- marginally reduced the risk for breast cancer recurrence, compared with stopping tamoxifen (617 vs 711; P = .002), reduced breast cancer mortality relatively by 8% (331 vs 397 deaths; P = .01) but that’s only about 1% in absolute terms, and reduced overall mortality by 10% (639 vs 722 deaths; P = .01). Over all, approximately 1/5 clinically relapsed, 1/7 deaths were from breast cancer; but of those who died, webfigures 4a and 4b of the supplementary appendix of the main ATLAS report showed that at autopsy almost half (43%) indeed had recurrent breast cancer. This gives the lie to early screening and treatment- 15 years later, even with tamoxifen for 10 years, early xray mammography detection and conventional surgical-radio-chemotherapy treatment does not cure much more than half of women with preclinical ER+ breast cancer that screening detects.The risk for recurrence by year 15 was 21.4% in the continuers group and 25.1% in the control group. ie only 3.7% absolute reduction. In addition, breast cancer mortality by year 15 was significantly reduced by nearly 3%; it was 12.2% in the continuers group and 15.0% in the control group. ie only 2.8% absolute reduction. Thus even in these women with early breast cancer, the cure rate even with tamoxifen was poor- slight reduction in the 25% recurrence and 15% breast cancer mortality rates. But almost half of the women who died had recurrence. Once again, the actual results published 4 months ago in the final Lancet report were much less impressive than the media release published 5 days later. Of these >6000 women allocated after initial surgery/ radio/chemotherapy to the tamoxifen or placebo trial, 85% did not die of breast cancer. But the cure rate was at best still only about 75%, and only half of those who died -by a mean of age 70 years – of any causes were free of breast cancer.
9 April 2013 Robert Stern at University of Arizona writes that “xray mammography alone is not a very good screening modality and has strikingly variable false positive, false negative, specificity, and efficacy rates, depending on what you read and who you believe.
8 April 2013: UPDATE: see vitamin D3 and Breast Cancer.
JAMA publishes on line from University Basel Switzerland, Shaw and Elger’s viewpoint on Evidence-Based Persuasion, often an ethical imperative to forcefully guide a hesitant patient into what seems to be the best decision, using arguments from Removal of Bias to Recommending Options and occasionally even Creating New Biases. The eternal problem remains, what is truly right? Is mass flu vaccine right? Is screening xray mammography truly lifesaving? especially if one quotes impressive but misleading relative risk reduction rather than in fact the crucial trivial absolute reduction? Is Directive Counselling however well-meant exercising undue influence? They conclude that it is an essential part of modern medical practice, without which it may be impossible to respect patients’ autonomy. Such necessary persuasion needs to meet 6 criteria.
updating the risks and futility of screening xray mammography.
There are certainly many safe natural ways we reviewed recently of reversing the risks of breast proliferation and cancer, thus justifying periodic safe low cost breast screening – mammo-imaging – by independent eg digital, mechanical tactile ” Sure Touch ” , ultrasound and/ or thermo- means.26 Feb 2013. There is a flood of new progress against breast disease , breast cancer and xray screening mammography: Contrary to the for-profit Breast industry, like all independent authorities including the Cancer Association of South Africa CANSA , the National Cancer Institute of America in 2013 no longer recommends routine xray mammography screening- it rates the EVIDENCE on X-ray screening mammography as FAIR evidence for its sole and arguable benefit – Decrease in total and breast cancer mortality – -*Consistency of studies is only Fair. External Validity: Good. Internal Validity: Variable,. But as GOOD evidence for the FIVE major HARMS of xray screening -* both consistency, internal & external validity -are good –
- Discomfort if not cellular rupture and bruising from violent 23 kg 50 lb crushing,
- Overdiagnosis and Resulting Treatment – including mastectomy or radiochemotherapy- of Insignificant Cancers:
- False-Positives with Additional Testing and Anxiety.
- False-Negatives with False senseof Security and Potential Delay in Cancer Diagnosis.
- Radiation-Induced Breast Cancer.
Winifred Cutler’s Athena Institute team warns again that screening X-ray mammography on well women is dangerous , inflicts terror, it does not reduce but may worsen the occurrence of invasive breast cancer. The Berkeley Institute’s Dr Venugopalan under profs Mina Bissell and Daniel Fletcher show that simply gentle massage helps – Compressing Breast Cancer Cells Can Stop Out-of-Control Growth Shelley Hwang ea show that in California simple lumpectomy for early breast cancer reduced deaths (up to 2009) by 28% compared to mastectomy. Belinski & Boyages at the Westmead Centre in Australia show again that common very low vitamin D levels more than double the risk of breast cancer let alone colon and all other cancers. A Harvard team (Liu ea) has just shown that the carnage of legalized poisoning (smoking – lungcancer, vascular; alcohol -liver disease, violence; adulteration with refined sugar/fructose – diabetes, vascular disease, cancer) aside, breast cancer far outstrips the other common cancers (colon, prostate cancer) in preventible life years lost. Willaims ea show again the major benefit of metformin against lethal breast cancer. Amadou ea in France confirm again the strong link between abdominal obesity and breast cancer from childhood throughout life. This again highlights the criminal stupidity of delaying metformin use till obesity let alone infertility or diabetes are established. Metformin can safely be introduced at any stage of life provided it is started at very low dose eg below 250mg/day and cautiously titrated to the maximum well-tolerated dose to avoid nausea and diarrhoea- and temporarily halved or stopped in case of intercurrent gastrointestinal upset. . Grani et al from Rome, Italy and many others remind us that both thyroid and breast malfunction are common by middle age and need to be sought and managed together. We know that in most aging populations, deleterious deficiency of especially magnesium, iodine, selenium, sulphur, and vits B, C, D and K , and melatonin and sex hormones is very common along with crippling multitoxic carcinogenic overload. So it is logical to use multisupplements, and massage anti- inflammatory anti-cancer antioxidant chelating antiestrogenic deep – penetrating iodine, coconut oil and DMSO – into the breasts as multidisease prevention and part of treatment. Oz ea in Turkey show that DMSO is more effective against breast cancer than thalidomide. But more importantly, DMSO enhances transport of any anticancer agents into cancer cells. Already in 2008 Frederick ea showed that Lugol’s Iodine is an important antiestrogen adjuvant against breast cancer. Hence we advise the harmless combination of natural multisystem micronutrients- especially fish oil, coconut oil, DMSO, vitamin C, D, K, melatonin, metformin, selenium, Lugol’s iodine and appropriate progesterone/ testosterone/ DHEA – as nutrient supplements against all chronic aging diseases especially in women at risk of breast cancer. . At Univ Newcastle on Tyne, Dr Dorota Overbeck-Zubrzycka’s landmark PhD thesis just published on FOXP3 regulates metastatic spread of breast cancer via control of expression of CXCR4 chemokine receptor promises new gene therapy in future. and her parallel study with Harvey, A. Griffiths & C. Griffith, Randomised control trial of Breast Tactile Imaging as an assessment tool for diagnosis of breast lumps in 2009/10 is now being published in full in a leading UK journal, validating this ( Sure Touch) bedside and outpatient clinic procedure as an established no-risk screening procedure, objective breast mapping record for anxious women as shown in USA, Indian and Chinese studies. Thus increasingly Authorities are accepting that screening X-ray mammography harms far outweigh trivial if any improvement in survival. But screening – by eg regular clinical exam and mechanical tactile mapping – for early signs of breast degeneration allows gentle safe self – treatment of all multisystem diseases that reverses both the breast degeneration and multisystem risk factors.
Editorial: Breast cancer screening: what does the future hold?
Personal View Harms from breast cancer screening outweigh benefits if death caused by treatment is included : Prof Michael Baum
BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f385 (Published 23 January 2013) Cite this as: BMJ 2013;346:f385
Thus they advise against screening people with an expected lifespan of below about 10 years. But who would undergo such bothersome risky screening even over 10 years for a proposed benefit (in death risk reduction) of 0.1% a decade ? They found the reasons against routine screening of those not at high risk ( ie no suspicious personal symptoms or familial history) are as usual those of the ensuing anxiety, the procedures – radiation and colonoscopy and biopsies – and overdiagnosis. The worst is of course the cumulative risk of breast irradiation, and perforation death from colonoscopy: “For cancer screening, about one in 10 patients who are screened (with xray mammography , or with fecal occult blood testing) will have a false positive result, leading to recall worry and likely biopsy/ colonoscopy. Serious complications (such as perforation, major bleeding, and death) occur in 3.1 colonoscopies per 1000 screened. One in 100 routinely mammography-screened women will be biopsied, and one in 1000 will be subject to overdiagnosis (that is, diagnosed with a breast cancer that was unlikely to have been clinically evident during their lifetime) and possibly unnecessary treatment.”
The same arguments apply strongly against routine screening of men for prostate cancer, or smokers for lung cancer, in the absence of symptoms. . It should be noted that even the Wikipedia Mammography review now strongly highlights the arguments against mass screening mammography. The introduction sums it up bluntly: “task force reports point out that in addition to unnecessary surgery and anxiety, the risks of more frequent mammograms include a small but significant increase in breast cancer induced by radiation. The Cochrane Collaboration (2011) concluded that mammograms reduce mortality from breast cancer by an absolute amount of 0.05% or a relative amount of 15%, but also result in unnecessary surgery and anxiety, resulting in their view that it is not clear whether mammography screening does more good or harm. They thus state that universal screening may not be reasonable. Mammography has a false-negative (missed cancer) rate of at least 10 percent. This is partly due to dense tissues obscuring the cancer and the fact that the appearance of cancer on mammograms has a large overlap with the appearance of normal tissues. A meta-analysis review of programs in countries with organized screening found 52% over-diagnosis.“
It can be argued that noninvasive screeing that finds suspicious premalignant signs can then motivate prevention by natural means- lifestyle diet and appropriate supplements. But since these preventative steps (including blood-pressure and waist/breast girth measurements and monthly self-exam for breast changes) hugely reduce the risks of all serious acute and chronic diseases, accidents and premature disability and death, routine mass screening for common ‘silent’ internal cancers eg breast, prostate colon lung womb and ovary , is irrelevant, risky and huge waste of resources for no benefit. Not applying sensible diet, lifestyle, blood-pressure checks and supplements is like failing to maintain your car, house, computers and electrical appliances etc , until these crucial assets break down. The evidence against hightech screening of the well of course does not stop the anxious well from worrying. As a heavy cigarette-smoking prof of lung medicine said 30 years ago, if an anxious patient demands a scope despite reassurance that the risk:benefit doesnt justify it, it is wise to do it. Or someone else will. At least in the context of the younger adult who will thereby be more motivated to apply prevention, non-xray non-invasive screening by eg Sure Touch breast mapping- from onset of menopause, or younger in eg diabetics and others more prone to cancer eg in AIDS, – and ultrasound quantitative bone-density risk measurement from toddlers upwards , in exercising ie sportspeople, and in any serious chronic disease especially with hormone overtones eg thyroid, diabetes, COPD/ asthma, cancer, arthritis, paralysis, AIDS,TB, cardiacs, renal, liver disease – are relatively low cost and safe compared to the traditional xray screening procedures. The brilliant new French movie The Intouchables is all about choices of lifestyle and the risks entailed. Thats what screening, and voluntary prevention, are about. No adult should be pressurized – by vested interests – into having hightech eg xray (breast, bone) or more invasive (eg scope, biopsy) screening without understandable explanation of the possible although infrequent immediate and distant risks, and remote if any benefits. Only the frequent incidental unexpected screening discovery of hypertension, increased breast lumpiness/density, and low bone density, and initiation of simple lifestyle diet changes and safe supplement therapy- the below- listed scores of supplements against all common degenerative diseases (and if needed the best primary antihypertensive – lowdose reserpine and co-amilozide – costs perhaps $1 a month to control most; and simple (breasts, arthritis, wound or elsewhere) antiinflammatory self massage if indicated with Lugol’s iodine, and analgesic antioxidant coconut oil and DMSO), gives huge early and permanent preventative pain and inflammatory benefits without risks. There are also promising studies on Pubmed between 1989 and 2011 of the benefits of DMSO in management of prostate problems in rats, and humans for transrectal procedures and intravenously as cancer adjuvant palliation. DMSO-MSM is cheaply and safely available . It comes back to basics that are anathema to politicians, Government, profiteers, Big Business Pharma and the Disease Industry. Motivating and enforcing better lifestyle and natural diet (minimizing sugar , aspartame, alcohol, processed food especially cornstarch) , and healthgiving realistic doses of supplements – vits (all – especially B, C, D3 and K), minerals (especially Mg, Zn, I2, Se, P, Bo,) and biological (plant and sealife – not land animal) extracts, (including fish oil, metformin, bioidentical human hormones, tryptophan, MSM, DMSO, chondroglucosamine, coconut oil, cinnamon, pepper, curcumin, arginine, carnitine, carnosine, ribose, coQ10, proline, rauwolfia) – reduces the occurrence of serious disease drastically with decades of health extension. This vastly reduces profit to the Disease Hospital-Drug and processed food- alcohol – tobacco industry in delayed disease till very old age, and thus loss of skilled workers’ jobs – that need to be taken up elsewhere. That’s called reinvention, recycling…
UPDATE: COLORECTAL CANCER SCREENING IN LOWRISK PATIENTS- NO BENEFIT ON ALL-CAUSE MORTALITY. IS IT ANYTHING BUT A HUGE EXPENSE- AND RISK?
21 Dec 2014 Update: No response has been received from or published by Annika Steffens ea of Australian universities in the past 2 months on the allcause mortality difference by CRC screening in their massive colorectal cancer CRC screening study in an older population. .
But a number of autopsy studies the past 40 years throw more light on how infrequent CRC actually is elsewhere , Australia apparently having one of the highest rates at 0.125% pa.
As regards apparently undiagnosed cancer found at autopsy: colon cancer is very infrequent, and its import drops with age; and is no more common in sudden death potential organ donors than in others. In Japan over 20 years, the incidence of unsuspected colon cancer in 3600 routine autopsies was only 0.03%pa. In Singapore in 1000 random autopsies on the other hand, incidental CRC was found in 10 ie a prevalence of 1%. In the Connecticut Cancer registry over 50 years, one cancer trebled the risk of a second cancer- especially high risk of cancers of lung, larynx, mouth, pharynx; breast;colon, uterus, ovary, cervix; suggesting a common etiology involving smoking & HPV? , ie an intriguing link between female genital tract, breast, airway and colon but not prostate.. However studies since at least 2005 including from RSA 2007, do indicate a link between HPV and prostate cancer, the latest from Crete University 2014.
So smoking, alcohol and STDs- especially HPV- are a deadly triad in male-dominated permissive countries like South Africa – but likely worse in strict Islamic countries that keep citizens (subjugated women even more than men) overdressed ie minimize sunshine and thus lifegiving vitamin D3 levels. .
refs: A new study from France asks: Are suicide rates higher in the cancer population? An investigation using forensic autopsy data. Med Hypotheses. 2014 de la Grandmaison, Charlier ea Versailles Saint-Quentin University, note previous population-based studies have identified increased suicide rates among cancer patients. In total, 232 cases were included in both the suicide and the control groups. Cancer was significantly more often found in the suicide group than in the control one (8.6% vs. 3.9%, p=0.03). the presence of cancer increased the risk of suicide. Moreover, cancer was not known to the deceased in 70% of cases, while the most frequent mental disease found in cancer-related suicide cases was depression (75%). In the 20 cancer-related suicide cases analysed herein, it was difficult to ascertain whether malignancy was the only motive for committing suicide, as cancer could be considered to be either a major causative factor for suicide or an incidental finding.
Crit Rev Oncol Hematol. 2012 Cancer prevalence and mortality in centenarians: a systematic review. Pavlidis , Audisio ea Univ of Ioannina,Greece. Data analysis demonstrates how cancer incidence and cause of death present a threefold decrease after age 90 and reach 0-4% above age 100. In addition, the number of metastatic sites are remarkably less and incidental malignant tumours or multiple primary cancers are more frequent, indicating that cancer in centenarians carries a more indolent behaviour. Cancer in the very elderly is relatively uncommon as a disease and as a cause of death. It is characterized by a slow growth and a modest life-threatening potential.
Arch Pathol Lab Med. 2009 Unexpected neoplasia in autopsies: potential implications for donor tissue safety. Sens, Cooley ea University of North Dakota.-Medical examiner cases are increasingly used as tissue donor referral sources to meet ever-growing need for transplant tissues. Assumption is often made that traumatic and sudden deaths have minimal risk of unsuspected neoplasia.-A retrospective, 5-year review of 412 autopsies from a regional, primarily forensic, autopsy service to determine the incidence of unsuspected neoplasia, potential donor referral suitability. Unsuspected neoplasia rate at autopsy was 7% (29 of 412 patients); cancer was the cause of death in 41% (12 of 29 patients) of these individuals. In patients with a history of cancer, the discordance of cancer diagnosis was 44% (4 of 9 patients [11 patients with known cancer, 2 who refused medical evaluation were excluded from the study]). Nearly 60% (17 of 29 patients) of the unsuspected cancer cases had no apparent reason for deferral of tissue procurement before the autopsy examination.
Cancer. 1988 Mar 1;61(5):1059-64. Incidental carcinoma of the colorectum at autopsy and its effects on the incidence and future trends of colorectal cancers in Singapore. Lee YS1. Ten incidental invasive carcinomas (two early carcinomas involving the submucosa, and eight advanced carcinomas involving the muscularis propria or beyond) of the large intestine were discovered in a series of 1014 consecutive autopsies. All occurred in Chinese aged 60 years and older, constituting a prevalence rate of about 3% in this age group. If unsuspected colorectal carcinomas in Chinese Singapore residents aged 60 years and older exist in those who died in 1984 to the same extent as that noted in this autopsy study, it was estimated that 146 additional cases would have been added to the Cancer Registry in that year. This would constitute 47.9% of the total number of colorectal cancers diagnosed in this age group in 1984. This potential contribution has to be taken into consideration in epidemiologic studies on the incidence and future trends of colorectal cancers in Singapore. It was observed further that incidental carcinomas were found predominantly in the ascending colon. With more frequent use of colonoscopy, the incidence of right-sided cancers of the large bowel may be expected to increase.
Natl Cancer Inst Monogr. 1985 Summary: multiple primary cancers in Connecticut, 1935-82. Curtis, Fraumeni ea The risk of developing a second primary cancer was evaluated in over 250,000 persons reported to the Connecticut Tumor Registry (CTR) during 1935-82. The CTR has collected data on cancer incidence longer than any other population-based tumor registry and thus provided researchers with a unique opportunity to investigate the occurrence of second cancers among persons followed for long periods, in some cases for more than 40 years. When compared with the general Connecticut population, cancer patients had a 31% increased risk of developing a subsequent cancer overall and a 23% elevated risk of second cancer at a different site from the first. Little variation in risk was seen for the first 20 years of follow-up, although the risk for females averaged twice that for males (41% vs. 18%). Persons who survived more than 20 years after the diagnosis of their first cancer were at highest risk: 51% for females and 45% for males. Over 1 million person-years of observation were recorded, and the excess risk of developing a new cancer was 3.5 per 1,000 persons per year. Common environmental exposures seemed responsible for the excess occurrence of many second cancers, particularly those related to cigarette smoking, alcohol consumption, or both. For example, persons with epithelial cancers of the lung, larynx, esophagus, buccal cavity, and pharynx were particularly prone to developing new cancers in the same or contiguous tissue throughout their lifetimes. A notable finding was the high risk of cancers of the lung, larynx, buccal cavity, and pharynx observed among cervical cancer patients, which suggested a common etiology involving cigarette smoking. The intriguing association previously reported among cancers of the colon, uterine corpus, breast, and ovary was confirmed in our data, which indicated the possible influence of hormonal or dietary factors. Incidental autopsy findings were largely responsible for the observed excesses of second cancers of the prostate and kidney, and heightened medical surveillance of cancer patients likely resulted in ascertainment bias and elevated risks for some tumors during the early period of follow-up, most notably cancers of the thyroid. Interestingly, patients with prostate cancer were the only ones found to be at significantly low risk for second cancer development. However, this might be an artifact of case-finding because advanced age at initial diagnosis of prostate cancer was associated with an underascertainment of second cancers.
J Am Geriatr Soc. 1979 Cancer in the aged: an autopsy study of 940 cancer patients. Ishii, Hosoda ea In an autopsy study of 940 elderly cancer patients, 1,030 cancers were identified. The prevalence rate for overall cancer declined after age 85 in men and after age 75 in women. The chief sites of major cancers were the stomach, lung, esophagus, liver, and pancreas, in that order. Incidental cancers (chiefly of the prostate, thyroid, and colon) were found more often in patients over 80 years old. For multiple primary cancers, the prevalence rate was relatively constant until the age of 70, when it rose to a peak in the 80–84 age group before declining to the original level
4 Nov 2014 update: a new POSTAL study Colorectal cancer CRC screening and subsequent incidence of colorectal cancer: results from the 45 and Up Study. by Steffen ea, from Australian universities shows the usual ~50% reduction BY SCREENING in colorectal cancer occurrence, in a population mean age 60yrs followed for a mean of 3.78yrs in 741 000 screened pts , mean 60yrs at screening, mean BMI 27kg ie a high-risk population . . But it glaringly omits mentioning the most important data: what was the allcause mortality reduction if any in the screened versus the unscreened cohorts after 3.78years? By this strange data omission, it must be assumed that the study showed no such benefit?.
All that the study confirmed is that it detected about 1000 new colon cancers in about 200 000 older people followed for almost 4 years ie an annual incidence of ~ 1 in 400 000 or 0.125% per year . This rate is similar to the 0.12% cases pa ie per year of early breast or prostate cancer claimed in USA SEER data; but the Australian CRC cancer rate reported is strangely almost three times the overall USA CRC incidence rate of about 0.04%pa found in USA men and women combined, similar to the lung cancer incidence reported there. . If the Australian data presented is correct, there must be something colotoxic (Perhaps their high beer and barbeque intake?) in the Australian diet compared to the European and USA population, since the great majority of all such citizens are of European “Caucasian” origin?
This compares to South Africa where the latest stats for the whole population (NRC/CANSA 2007) (assuming only maybe <1/4 of the population are 45yrs and up) are : prostate or breast 0.05%pa, lung or CRC 0.01%pa, and cervix (much younger- due to abuse and STD) 0.05%pa. That study reported the lifetime risk of CRC in RSA as 1:115 in men, 1:199 in women, compared to , prostate 1:26 and breast 1:35, cervix 1:42, uterus 1:176, lung men 1:91 women 1:250.
There remains no good evidence of lives saved ie reduction in all-cause mortality by such hugely costly population cancer screening for these commonest cancers. All that it achieves is the knowledge of previously silent cancer, which would mostly have been buried unknown with the patient dying of other common causes- ie creating the worried well who have become “cancer survivors”.
we await response from the authors on this primary issue .
19 Sept 2014 . is there anything to update? CONCLUSION: not really. Conservatism urges avoidance of screening anyway in those with short lifespan from other major disease, or age eg above 75years- UNLESS there is good evidence of meaningful life extension. As we concluded in 2011, is such screening worth perhaps 1 month life extension in old age?
So far there is still no good evidence to support regular mass population screening in apparently well adults without risks for any degenerative disease EXCEPT for hypertension; glaucoma; malignant melanoma; and women at risk of cervix cancer ie sexually active at a younger age.
Health benefits and cost-effectiveness of a hybrid screening strategy for colorectal cancer. Dinh T, Levin TR ea 1Archimedes Inc, San Francisco present a model rationale for FOBT screening from age 50yrs, with a single elective colonoscopy at 66yrs if FOBT remains negative – at a cost of US$10000 per putative QALY gained. . Colorectal cancer (CRC) screening guidelines recommend screening schedules for each single type of test except for concurrent sigmoidoscopy and fecal occult blood test (FOBT). We investigated the cost-effectiveness of a hybrid screening strategy that was based on a fecal immunological test (FIT) and colonoscopy. METHODS: We conducted a cost-effectiveness analysis by using the Archimedes Model to evaluate the effects of different CRC screening strategies on health outcomes and costs related to CRC in a population that represents members of Kaiser Permanente Northern California. The Archimedes Model is a large-scale simulation of human physiology, diseases, interventions, and health care systems. The CRC submodel in the Archimedes Model was derived from public databases, published epidemiologic studies, and clinical trials. RESULTS: A hybrid screening strategy led to substantial reductions in CRC incidence and mortality, gains in quality-adjusted life years (QALYs), and reductions in costs, comparable with those of the best single-test strategies. Screening by annual FIT of patients 50-65 years old and then a single colonoscopy when they were 66 years old (FIT/COLOx1) reduced CRC incidence by 72% and gained 110 QALYs for every 1000 people during a period of 30 years, compared with no screening. Compared with annual FIT, FIT/COLOx1 gained 1400 QALYs/100,000 persons at an incremental cost of $9700/QALY gained and required 55% fewer FITs. Compared with FIT/COLOx1, colonoscopy at 10-year intervals gained 500 QALYs/100,000 at an incremental cost of $35,100/QALY gained but required 37% more colonoscopies. Over the ranges of parameters examined, the cost-effectiveness of hybrid screening strategies was slightly more sensitive to the adherence rate with colonoscopy than the adherence rate with yearly FIT. . CONCLUSIONS: In our simulation model, a strategy of annual or biennial FIT, beginning when patients are 50 years old, with a single colonoscopy when they are 66 years old, delivers clinical and economic outcomes similar to those of CRC screening by single-modality strategies, with a favorable impact on resources demand. Clin Gastroenterol Hepatol. 2013 Sep;:1158-66.
16 Sept 2014: PREVENT INSTEAD OF SCREEN: Dr Ng from DANA FABER CANCER INST, BOSTON MASS asks in . Vitamin D for Prevention and Treatment of Colorectal Cancer: What is the Evidence? Vitamin D insufficiency is highly prevalent in the U.S, particularly among colorectal cancer (CRC) patients- – studies suggest that higher vitamin D levels are associated with lower risk of incident CRC as well as improved survival in patients with established CRC. There remains a great need to improve prognosis for patients with CRC, and investigating vitamin D as a potential therapeutic modality is an attractive option in regards to safety and cost, particularly in this era of expensive and often toxic anti-neoplastic agents. Curr Colorectal Cancer Rep. 2014 Sep 1;10:339-345
But as we know well from many studies, conventional “high” doses of vitamins C (eg hundreds of mgs/d) and D (a few hundred to a few thousand iu/d) have only modest benefit for prevention and against existing disease- it requires about 10-15fold higher vit D3 ie 80-100iu/kg/day, and 100 to 500 more vit C ie a few to a few score gms vit C a day to have major impact. These must not be in isolation, as they may be limited by conditioned deficiency of other micronutrients especially vits K2. . We know well from eg the ATBC trial of vits A and E that too much and too late may be harmful, especially if these are not in natural balanced forms of all the vits A and E groups.
14 Sept 2014 A colleague is surprised that at 72yrs I have never had a screening scope.
so I recheck the evidence after 3 years, since my 2011 review. Even The USA National Cancer Institute review of colon cancer screening (updated to 24 July 2014) agrees that Based on solid evidence, there is little evidence that screening for colorectal cancer (CRC) reduces all-cause mortality, possibly because of an observed increase in other causes of death, although in some studies it may reduce CRC mortality; and there is always serious risk of harms. Overall, the NCI concludes that On initial (prevalence) examinations, from 1% to 5% of unselected persons screened with stool gFOBT guaiac faecal occult blood test (collected over 3 days, repeated up to yearly ) have positive test results ie 30 per 1000 recalled; of whom on imaging 2% to 10% have cancer and approximately 20% to 30% have adenomas,[26,27] depending on how the test is done.That translates to colon cancer detected in about 3% of 6% = 0.18% of the target population screened – of whom 74% occur between 55 and 84 yrs. .
As a recent Spanish team review last year says, No strategy, whether alone or combined, has proven definitively more effective than the rest: Economic evaluation of colorectal cancer (CRC) screening. Cruzado J1, Carballo F. ea 1Colorectal Cancer Prevention Program for Instituto Murciano de Investigación Biosanitaria, Murcia, Spain Because of its incidence and mortality colorectal cancer represents a serious public health issue in industrial countries. In order to reduce its social impact a number of screening strategies have been implemented, which allow an early diagnosis and treatment. These basically include faecal tests and (then) studies that directly explore the colon and rectum. No strategy, whether alone or combined, has proven definitively more effective than the rest, but any such strategy is better than no screening at all. Selecting the most efficient strategy for inclusion in a population-wide program is an uncertain choice. Here we review the evidence available on the various economic evaluations, and conclude that no single method has been clearly identified as most cost-effective; further research in this setting is needed.. Best Pract Res Clin Gastroenterol. 2013 ;27:867-80.
BUT: Is aging per se a real risk factor for suffering colon cancer? No good evidence yet. all cancers do increase with aging. But there is still no hard evidence of meaningful life extension from colon, breast or prostate screening for silent risks in those without other cancer risk factors.
The NCI found four completed trials of FOBT faecal occult blood testing since 2004 – in Minneapolis(46500), Denmark (31000), Sweden(68000) and UK(151000) – ie 300 000 older lowrisk adults- these find no benefit in terms of increased length of life. The longest, – 30 year followup in Minneapolis – looks at the longterm mortality benefit of CRC screening– and as with breast and prostate screening for silent cancer in those without significant risk factors. So organized mass population screening eg every 1 or 10 years from age 50 years does not save lives in the elderly at low risk ie no colon symptoms- at an enormous cost in the scores of well people – about 1.2 per 1000- needed to screen, with about 3% of these found positive needing imaging- at major risk of unforseen problems- to find one cancer, shorten the lead time, save a life from silent cancer. We all die from something eventually. 99.82% of the population screened did not develop colon cancer.
In firstworld people the risk of colon cancer is generally below that of breast and prostate cancer respectively: Wiki sums it up- Based on rates from 2007-2009, 5% of US men and women born today will be diagnosed with colorectal cancer during their lifetime. The median age at diagnosis for cancer of the colon and rectum in the US was 69 years of age. Approximately 0.1% were diagnosed under age 20; 1.1% between 20 – 34; 4.0% between 35 – 44; 13.4% between 45 – 54; 20.4% between 55 a-64; 24.0% between 65 – 74; 25.0% between 75- 84; and 12.0% 85+ years. Rates are higher among males (54 per 100,000 c.f. 40 per 100,000 for females). about 20% of such cancer patients have a familial genetic risk.
so faecal screening would be the mass screening method of choice, with about 25% recall rate for costly colon imaging to find the 1.2 cases per 1000 in the target population. But that is supposed to uncover silent colon cancer 2 years earlier, allowing expected drastic reduction in the 75% mortality of clinically presenting colon cancer. So why do no trials of colon cancer screening show reduction in all-cause mortality? Perhaps its because the lethal colon cancers occur and present clinically younger in those with lethal genetic risks eg Lynch syndrome, or predisposing colon inflammation eg ulcerative colitis, Crohn’s; or those with multiple polyposis who are more likely to bleed early.
But we know that real chronic colonic disease is par excellence a western Saccharine Disease ie of our urban fastfood high sugars, low fibre diet, inadequate water intake, and slothful low sunshine ie couch potato low vitamin D constipated lifestyle; with often smoking and alcoholism. . Naturally the Wiki review, written to favour regular screening to find profitable more silent cancers (like breast and prostate screening) , does not mention this. .
Shaukat A1, Church TR ea (in N Engl J Med. 2013;369:1106-14 Long-term mortality after screening for colorectal cancer. Minneapolis VA Health Care System USA). In randomized trials, fecal occult-blood testing FOBT reduces mortality from colorectal cancer. However, duration of the benefit is unknown, as are the effects specific to age. METHODS: In the Minnesota Colon Cancer Control Study, 46,551 participants, 50 to 80 years of age, were randomly assigned to usual care (control) or to annual or biennial screening with fecal occult-blood testing. Screening was performed from 1976 through 1982 and from 1986 through 1992. We used the National Death Index to obtain updated information on the vital status of participants and to determine causes of death through 2008. RESULTS: Through 30 years of follow-up, 33,020 participants (70.9%) died. A total of 732 deaths 2% were attributed to colorectal cancer: 200 of the 11,072 deaths (1.8%) in the annual-screening group, 237 of the 11,004 deaths (2.2%) in the biennial-screening group, and 295 of the 10,944 deaths (2.7%) in the control group. Screening reduced colorectal-cancer mortality (relative risk with annual screening, 0.68; 95% confidence interval [CI], 0.56 to 0.82; relative risk with biennial screening, 0.78; 95% CI, 0.65 to 0.93) through 30 years of follow-up. No reduction was observed in all-cause mortality (relative risk with annual screening, 1.00; 95% CI, 0.99 to 1.01; relative risk with biennial screening, 0.99; 95% CI, 0.98 to 1.01). The reduction in colorectal-cancer mortality was larger for men than for women in the biennial-screening group (P=0.04 for interaction). CONCLUSIONS: The effect of screening with fecal occult-blood testing on colorectal-cancer mortality persists after 30 years but does not influence all-cause mortality. The sustained reduction in colorectal-cancer mortality supports the effect of polypectomy.
For mass Sigmoidoscopy screening, Five sigmoidoscopy screening RCTs have reported incidence and mortality results.- Norway 2 trials; and United Kingdom; Italy; and the U.SA, in 166,000 participants in the screened groups and 250,000 controls. Follow-up ranged from only 6 to 13 years. There was an overall 28% relative reduction in CRC mortality (RR, 0.72; 95% CI, 0.65–0.80), an 18% relative reduction in CRC incidence (RR, 0.82; 95% CI, 0.73–0.91), and a 33% relative reduction in the incidence of left-sided CRC (RR, 0.67; 95% CI, 0.59–0.76). There was no effect on all-cause mortality.
For mass colonoscopy screening, no trials have been completed to give any evidence of longterm mortality benefit.
One group proposes a screening program based on periodic stool FIT faecal immunological test , with a single colonoscopy at 66yrs. Dinh , Levin ea Archimedes Inc, San Francisco,( Clin Gastroenterol Hepatol. 2013 ;11:1158-66 Health benefits and cost-effectiveness of a hybrid screening strategy for colorectal cancer) In our simulation model, a strategy of annual or biennial FIT, beginning when patients are 50 years old, with a single colonoscopy when they are 66 years old, delivers clinical and economic outcomes similar to those of CRC screening by single-modality strategies, with a favorable impact on resources demand.
UPDATE 20 Oct 2011 A chiropracter asks: what is the recommendation regarding screening colonoscopy, mammography, prostate for cancers? would MD’s and DO’s get one and if so in what circumstance?
The only link between breast, prostate, bowel, ovary and womb cancers is that these organs (unlike cervix cancer) are genetically linked through common sex hormone influences; and (apart from the breasts) coincidentally abut ..
Prostate cancer associates with higher estrogen and DHT levels. As for usually estrogen-dependent breasts and breast cancer screening in low-risk breasts discussed previously, the overwhelming evidence favours no screening at all without symptoms or risk factors. Unlike for breast cancer, treatment for prostate cancer (as for colon cancer) seems to make no difference except when there is obstruction or bleeding. For asymptomatic PRCA the rule remains: watchful waiting. Like women and breast cancer, many men have undiagnosed ie asymptomatic prostate cancer at autopsy for other causes of death.
Colon cancer is different. it is less common in women with estrogen replacement.
But unlike prostate and breast cancer where invasive screening of all lowrisk patients likely causes more harm (including despondency) than good, it is hard to find good colon cancer studies of asymptomatic lowrisk people that show no benefit of screening colon imaging. Studies of colon cancer imaging are inevitably by practitioners who have a major commercial vested interest in such imaging.
But how many studies have been done comparing colon screening with no screening in patients who truly have none of the risk factors – – heredity, meat diet, smoking, overweight, bleeding, inflammatory bowel disease, polyps, diabetes?
Few articles are against such colon screening ie rationalize or philosophize against it .
A 2011 Medscape review from a New Jersey University team concludes cautiously: “In particular, education and intervention efforts for colon imaging should be focused on patients that have risk factors eg diabetes, obesity, or are former/current smokers. This population represents a sub-group of patients who are having CRC screening at a rate lower than the average-risk population. Significant reductions in CRC incidence and mortality might be possible by providing targeted screening interventions to increased-risk individuals and by educating physicians on the importance of recommending screening to these patients even in the face of multiple competing demands”. ie it encourages colon screening in increased risk individuals.
Search of Pubmed for “incidental colon cancer at autopsy” reveals only three studies, >20 years ago, two in the orient.
Ueyama ea, Kyushu University, Japan in Am J Gastroenterol.1991 Colorectal carcinomas incidentally detected in 3,638 autopsied cases and inpatients during the past 20 yr. 17 colorectal carcinomas (0.47%) were incidentally detected among autopsied patients without clinically evident colorectal carcinoma, including 2,232 males and 1,406 females more than 40 yr old. Among the 15 male and two female index subjects, six (0.33%) were detected in the first and 11 (0.60%) in the second decade. During their survival periods, fecal occult blood studies were performed in 14 cases and positive in 12 (86%); however, two of them had gastric ulcers which were responsible for the occult blood. During the recent 11 yr, six cases (0.48%) of colorectal carcinoma (four of them males; two, females) also were detected among 1,249 inpatients who were examined by barium enema and/or colonoscopy, including 816 males and 433 females, 40 yr old, or more, in the Department of Radiology. Fecal occult blood was detected in four cases (67%) before colonic investigation. Compared with 708 surgically resected carcinomas, the incidental lesions from both sources were smaller, consisted of higher percentages of Dukes’ A type, and arose predominantly from the sigmoid colon and, rarely, from the rectum. These results indicate that the prevalence of colorectal carcinoma and its predominance in the sigmoid colon have not only apparently but actually increased in Japan, apart from improved diagnostic capabilities, and that false-negative rates with occult blood tests were surprisingly low in these autopsied cases and inpatients.
- Lee YS in Cancer 1988 studied Incidental carcinoma of the colorectum at autopsy in Singapore. . . Ten incidental invasive carcinomas (two early carcinomas involving the submucosa, and eight advanced carcinomas involving the muscularis propria or beyond) of the large intestine were discovered in a series of 1014 consecutive autopsies. All occurred in Chinese aged 60 years and older, constituting a prevalence rate of about 3% in this age group. If unsuspected colorectal carcinomas in Chinese Singapore residents aged 60 years and older exist in those who died in 1984 to the same extent as that noted in this autopsy study, it was estimated that 146 additional cases would have been added to the Cancer Registry in that year. This would constitute 47.9% of the total number of colorectal cancers diagnosed in this age group in 1984. This potential contribution has to be taken into consideration in epidemiologic studies on the incidence and future trends of colorectal cancers in Singapore. Incidental carcinomas were found predominantly in the ascending colon. With more frequent use of colonoscopy, the incidence of right-sided cancers of the large bowel may be expected to increase. The current underdiagnosis of ascending colon carcinomas has to be taken into consideration when any future increase in right-sided cancers of the large bowel is observed.
Suen ea Cancer. 1974 studied Cancer and old age – autopsy study of 3,535 patients over 65 years old, in New York from 1960 to 1970 ie a decade earlier than the above oriental studies; they showed that men had cancer nearly twice as frequently as women (40% vs. 24%); and more incidental ie less aggressive neoplasms as age advanced. The most frequent cancers were those of the prostate (12% of men), gyne (7.5% of women- breast 3%) , kidney 3.5%, and colon 5.6%.. 70% of the cancers were already diagnosed in life ie 30% were incidental findings. Cancer tended to metastasize less frequently in the elderly. The most common sites of latent asymptomatic cancer reported by Berg et al The prevalence of latent cancers in cancer patients. Arch. Pathol 1971. in their study of 5636 cancer patients with ages ranging from the teens to over 80,were prostate, thyroid, colon, and kidney. They further emphasized that cancer of the colon and kidney were the ones most easily missed clinically. In our study, the most frequent sites of incidental cancer, among the common cancers, were prostate (incidental 67%), kidney (51%), colon (31.5%), and breast 16.6%.
And researchers from the Universities of California, North Carolina and Harvard – Walter ea– show in 2005 Screening for colorectal, breast, and cervical cancer in the elderly: Am J Medicine that “characteristics of individual patients that go beyond age should be the driving factors in screening decisions… in one study -Selby ea A case-control study of screening sigmoidoscopy and mortality from colorectal cancer . N Engl J Med . 1992; .”For colorectal cancer screening, fecal occult blood testing has the strongest evidence of benefit in elderly patients, while flexible sigmoidoscopy reduces mortality from colorectal cancer by 59% .Flexible sigmoidoscopy has fewer complications than colonoscopy, with perforations occurring in less than 0.1 of 1000 examinations; .” But they did not report data on benefit of colorectal screening of lowrisk adults in terms of actual overall life extension ie reduction in all-cause mortality- which benefit has not been shown in rigorous analysis of xray screening mammography or screening blood and digital exams of lowrisk men for prostate cancer. .
Lack of significant life extension by breast and colon screening was shown by Rich and Black from Vermont USA in Clin Pract. 2000 When should we stop screening? Given a starting age of 50 years, screening throughout life has a maximum potential life expectancy benefit of 43 days for breast cancer and 28 days for colon cancer.
These 1 month extensions in life expectancy do not justify screening the entire population of older persons- surely only those of us with significant risk factors need be screened.
CONCLUSION: from the above references from autopsy series, the prevalence of incidental ie asymptomatic colon cancer at routine autopsy in older deaths varies between about 0.5% and 3% in oriental and New York patients. So since I dont have any symptoms or risk factors listed, after 50 years in medicine I havent had colon or prostate imaging for a potential 4 week gain in life expectancy. I will do so promptly if I get colon symptoms.
I tell my older lowrisk patients the dubious potential benefit of cancer screening, and the serious risks, from overdiagnosis- polyps and lowgrade cancers that might never present in lifetime, to perforation ; while explaining to them that well-patient breast, prostate and colon cancer screening is hugely profitable universal policy.
For non-emergency consultations and especially costly and invasive procedures, doctors and patients need reminding that it’s the patient’s choice, not the doctors’..
This brings us to one of the ethical dilemmas of medicine: when our experience, and careful sifting of the hard evidence, conflicts with conventional wisdom- which is often based on belief and vested interests- evidence slanted hy bias- surely we practitioners have both a right to express our evidence-based personal conviction, and a duty to do so. Thus we surely have a duty to give the patient the hard evidence both for and against- be it about the power of prayer and belief, about contraception and abortion, for and against statins for mild-moderate lipidemia, or in the low-risk patient, screening mammography, prostate or colon screening.
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for appointments for consultations, or non-xray procedures by registered practitioners : Sure Touch breast prescreening on Saturday mornings next on 7 February 2015 by Sister Zeneath Ismail – cash R650 (then R450 if followup scan desired within 3 months); -QUS ultrasound quantitative bone density cash R450 -tariff item 3612- anytime; Unlike radiologists’ and thermography reports (which describe only the imaging finding), the rates quoted include relevant breast or bone consultation and management planning by specialist nurse & physician.
IF BOOKED TOGETHER, (not necessarily the same morning) then combined breast and bone screening is R1000.
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Thermography no-touch infrared screening for suspicious cancer /inflammatory changes: by Radiographer Melinda-next 23 March 2015. R900 breasts; R1100 head and upper; or lower body & pelvis; R1300 whole body.
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Under CMS Council for Med Schemes Reg 10(6), open Medical schemes eg hospital plans have to pay from their own funds (not members’ savings) for appropriate outpatient consultation (tariff item 0191) for PMBs ie major conditions eg cancer, depression, neck/spinal problems, serious heart, lung, other disease., etc. Breast and osteoporosis concerns are generally part of menopause consultations N95.9 (if not already eg breast cancer code C50) and thus are often billable med scheme benefits. The menopause billable item only applies if you are 45yrs upwards, unless you have had total hysterectomy.
On patients’ requests, appropriate invoice can be prepared and submitted to your scheme for refund of your due benefits. Some schemes eg hospital plans falsely deny due benefits until reported to their regulator CMS. For medical plans where the billable tariff benefit rate is higher than the breast screening fee paid, the med plan rate 0191 will be charged eg R790 by the contracted specialist, and refundable by Discovery to the member. some basic schemes eg Keycare, Bonitas require preauthorization, or referral by their contracted GP .
29 SEPT 2014 OVARIAN CANCER UPDATE: PROGESTERONE REPLACEMENT IS IDEAL; WHY USE ORAL HT? WHEN ESPECIALLY LONG TERM PROGESTINS GREATLY INCREASE RISK OF OVARIAN AS WELL AS BREAST CANCER.
: ABSTRACT: since last review in this column 5 years ago, what progress has there been with ovarian cancer OvCa? On Pubmed there are 81000 references, 45500 reviews on OvCa
5 Oct 2014: Ovarian Cancer Often Arises from Precursor Endometriosis Frontline Medical News, 2014 Sep 29,
29 Sept 2014 The good news is that if ovariectomy is not done at hysterectomy, then at least salpingectomy should be done- it does not cause earlier menopause. And the modern fashion for progesterone cream as baseline hormone balancing in this age of estrogen dominance, the feminization of nature, also adds major protection for heart, bone, memory, mood, and against cancer, without the risks of estrogen.
Before this month’s update, the latest, an Australian cancer review Mette ea 2013, shows that cigarette smoking increases the risk of OvCa by 30% to 60%.
The latest review 2013 Modugno ea at Univ Pittsburgh/Mayo Clinic Hormone response in ovarian cancer: time to reconsider as a clinical target? said “Ovarian cancer is the sixth most common cancer worldwide among women in developed countries and the most lethal of all gynecologic malignancies. There is a critical need for the introduction of targeted therapies to improve outcome. Epidemiological evidence suggests a critical role for steroid hormones in ovarian tumorigenesis. There is also increasing evidence from in vitro studies that estrogen, progestin, and androgen regulate proliferation and invasion of epithelial ovarian cancer cells. Limited clinical trials have shown modest response rates; however, they have consistently identified a small subset of patients that respond very well to endocrine therapy with few side effects. We propose that it is timely to perform additional well-designed trials that should include biomarkers of response.The most consistently reported reproductive and hormonally related factors found to protect against EOC are use of oral contraceptives (OCs), increasing parity, and having a tubal ligation. In contrast, increasing age and nulliparity have been consistently shown to increase EOC risk.
Recent studies, including the prospective Women’s Health Initiative (WHI) (Anderson et al. 2003) and the Million Women Study (Beral et al. 2007), report an increase in risk for both estrogen-only (ET) and estrogen–progestin (EPT) formulations, although the risk associated with EPT was lower than that of ET. A recent meta-analysis of 14 published studies found risk increases 22% per 5 years of ET use compared with only 10% per 5 years of EPT use, suggesting that risk differs by regimen (Pearce et al. 2009). Exogenous androgens may be associated with EOC. One case–control study found that use of Danazol, a synthetic androgen commonly used in the treatment of endometriosis, significantly increased EOC risk (Cottreau et al. 2003), although this finding has not been replicated (Olsen et al. 2008). Ever use of testosterone (tablets, patches, troches, or cream) has been associated with a threefold increase in EOC (Olsen et al. 2008).
Reproductive disorders and other reproductive factors : Factors affecting childbearing have also been shown to be associated with EOC. In most studies, infertility has been associated with an increased risk, which may be greatest among women who fail to conceive (Vlahos et al. 2010). In general, infertility treatment does not appear to increase EOC risk, although the subset of treated women who remain nulliparous may be at an increased risk (Vlahos et al. 2010).
Endometriosis, defined as the presence and growth of endometrial tissue outside the uterine cavity, has also been associated with EOC. A recent pooled analysis of 13 case–control studies showed a threefold increase in the incidence of clear cell EOC and a twofold increase in endometrioid EOC among women with a self-reported history of endometriosis (Pearce et al. 2012).
An increased risk of EOC was reported by one case–control study (Schildkraut et al. 1996) among women with polycystic ovary syndrome (PCOS), a condition associated with menstrual dysfunction, infertility, obesity, the metabolic syndrome, hyperandrogenism, and insulin resistance. However, the finding was based on a small number of cases (n=7) and the association was limited to nonusers of OCs and thin women. Further case–control and prospective studies have failed to confirm this relationship (Pierpoint et al. 1998, Olsen et al. 2008, Brinton et al. 2010).
Tubal ligation has been consistently shown to be associated with reduction in EOC risk (Cibula et al. 2011). This protection appears similar in magnitude to OC use and child bearing (about 30%) and is protective in high-risk women (i.e. BRCA1/2 carriers) as well. Hysterectomy has also been shown to reduce EOC risk, although the magnitude of the association is not as great nor as consistent as that reported for tubal ligation (Riman et al. 2004). Finally, reproductive factors associated with other hormonally linked cancers, such as age at first menarche, age at menopause, and length of reproductive years, have not been consistently associated with EOC (Riman et al. 2004).
Estrogens and androgens – The evidence linking these to EOC are mixed. The majority of women who develop ovarian cancer are postmenopausal at the time of diagnosis. In postmenopausal women, the major source of circulating estrogen is from the peripheral conversion (in skin and adipose tissue) of androstenedione by the enzyme aromatase.
Progesterone and progestins- Epidemiological data suggest that progestins and progesterone may have a protective role against EOC. Importantly, there is some evidence that progesterone might synergize with chemotherapeutic drugs to induce apoptosis.
Now this month comes exciting news about a Paradigm Shift: Prophylactic Salpingectomy for Ovarian Cancer Risk Reduction Frontline Medical News, 2014 Sep 24, Removing the fallopian tubes at the time of pelvic surgeries as a potential means of reducing ovarian cancer risk appears to be a movement that’s picking up steam in clinical practice.
A recent survey of 234 U.S. gynecologists showed prophylactic bilateral salpingectomy is catching on when performed in conjunction with hysterectomy, but far less so for tubal sterilization, Dr. Austin Findley observed at the annual Minimally Invasive Surgery Week. A total of 54% of respondents indicated they routinely perform salpingectomy at the time of hysterectomy in an effort to reduce the risk of ovarian cancer as well as to avoid the need for reoperations. However, only 7% of the gynecologic surgeons said they perform salpingectomy for tubal sterilization, even though 58% of respondents stated they believe the procedure is the most effective form of tubal sterilization (J. Minim. Invasive Gynecol. 2013;20:517-21).
“In my experience at various hospitals, I think these numbers are a pretty accurate reflection of what folks are doing,” commented Dr. Findley of Wright State University in Dayton, Ohio.
The prophylactic salpingectomy movement is an outgrowth of the tubal hypothesis of ovarian cancer.
“There is now increasing and dramatic evidence to suggest that most ovarian cancers actually originate in the distal fallopian tubes. I think this is a concept most people are unaware of or are just becoming accustomed to. The tubal hypothesis represents a major paradigm shift in the way we think about ovarian cancers. The previous belief that excessive ovulation is a cause of ovarian cancer is no longer regarded as accurate,” he explained at the meeting presented by the Society of Laparoscopic Surgeons and affiliated societies.
Ovarian cancer is the No. 1 cause of mortality from gynecologic malignancy, accounting for more than 14,000 deaths per year, according to National Cancer Institute data. The lifetime risk of the malignancy is 1.3%, with the average age at diagnosis being 63 years.
Only 10%-15% of ovarian cancers occur in women at high risk for the malignancy because they carry a BRCA mutation or other predisposing gene. The vast majority of ovarian cancer deaths are caused by high-grade serous tumors that have been shown to be strongly associated with precursor lesions in the distal fallopian tubes of women at low risk for the malignancy.
There is no proven-effective screening program or risk-reduction method for these low-risk women. However, with 600,000 hysterectomies and 700,000 tubal sterilizations being performed annually in the United States, prophylactic salpingectomy has been advocated as an attractive opportunity to potentially reduce ovarian cancer risk. Other common pelvic surgeries in which it might be used for this purpose include excision of endometriosis and laparoscopy for pelvic pain. It also has recently been shown to be feasible and safe post partum at cesarean or vaginal delivery (Obstet. Gynecol. 2014 [doi: 10.1097/01.AOG.0000447427.80479.ae]).
But the key word here is “potentially.” It must be emphasized that at present the ovarian cancer prevention benefit of prophylactic salpingectomy remains hypothetical; in theory, the procedure should reduce ovarian cancer risk, but there is not yet persuasive evidence that it actually does, Dr. Findley emphasized at the meeting, presented by the Society of Laparoendoscopic Surgeons and affiliated societies.
In contrast, one well-established ancillary benefit of prophylactic salpingectomy is that it eliminates the need for future reoperation for salpingectomy. This was demonstrated in a large Danish cohort study including close to 10,000 women undergoing hysterectomy and a similar number undergoing sterilization procedures. Among the nearly two-thirds of hysterectomy patients who had both fallopian tubes retained, there was a 2.13-fold increased likelihood of subsequent salpingectomy, compared with nonhysterectomized women.
Similarly, Danish women who underwent a sterilization procedure with retention of the fallopian tubes – typically tubal ligation with clips – were 2.42 times more likely to undergo subsequent salpingectomy, most often because of the development of hydrosalpinx, infection, ectopic pregnancy, or other complications (BMJ Open 2013;3 [doi:10.1136/bmjopen-2013-002845]).
The most commonly cited potential risk of prophylactic salpingectomy – decreased ovarian function – now appears to be a nonissue. This was demonstrated in a recent retrospective Italian study (Gynecol. Oncol. 2013;129:448-51) as well as in a pilot randomized controlled trial conducted by Dr. Findley and his coworkers (Fertil. Steril. 2013;100:1704-8), which appears to have answered many skeptics’ concerns. Indeed, Dr. Findley’s coinvestigator Dr. Matthew Siedhoff said he has recently been approached by researchers interested in collaborating in a larger confirmatory randomized trial, but all parties eventually agreed it was a no-go.
“It’s a little hard to demonstrate equipoise for a larger randomized controlled trial. We’re beyond that now, given that prophylactic salpingectomy really doesn’t seem to make a difference as far as ovarian function,” according to Dr. Siedhoff, director of the division of advanced laparoscopy and pelvic pain at the University of North Carolina, Chapel Hill.
Another oft-expressed reservation about salpingectomy as a means of reducing ovarian cancer risk in women seeking sterilization is that salpingectomy’s irreversibility may lead to “tubal regret” on the part of patients who later change their mind about further pregnancies. However, Dr. Findley cited a recent editorial whose authors criticized colleagues who made that claim. The editorialists argued that the tubal regret concern indicates surgeons weren’t really listening to their patients’ true desires during the informed consent conversation.
“We should not have started thinking about salpingectomy for female sterilization only once a decrease in ovarian cancer risk became part of the equation,” they declared (Obstet. Gynecol. 2014;124:596-9).
Dr. Findley noted that Canadian gynecologists are leading the way forward regarding prophylactic salpingectomy as a potential method of ovarian cancer prevention. The Society of Gynecologic Oncology of Canada in a 2011 policy statement recommended patient/physician discussion of the risks and benefits of bilateral salpingectomy for patients undergoing hysterectomy or requesting permanent sterilization. The Society of Gynecologic Oncology followed suit with a similar clinical practice statement in late 2013.
Additionally, the Canadian group declared that a national ovarian cancer prevention study focused on fallopian tube removal should be a top priority.
Gynecologic oncologists in British Columbia recently reported the eye-catching results of a province-wide educational initiative targeting gynecologists and their patients. In 2010, all British Columbia gynecologists had to attend a course on the role of the fallopian tubes in the development of ovarian cancer, during which they were advised to consider performing bilateral salpingectomy for ovarian cancer risk reduction.
Surgical practice changed dramatically in British Columbia in response. In 2009 – the year prior to the physician education initiative – salpingectomy was utilized in just 0.3% of permanent sterilization procedures. In 2010, it was 11.4%. By 2011, it was 33.3%.
Similarly, only 7% of hysterectomies performed in British Columbia in 2009 were accompanied by bilateral salpingectomy. This figure climbed to 23% in 2010 and jumped further to 35% in 2011. Meanwhile the rate of hysterectomy with bilateral salpingo-oophorectomy remained steady over time at 44% (Am. J. Obstet. Gynecol. 2014;210:471.e1-11).
This project was conducted in collaboration with the B.C. Cancer Agency, which maintains comprehensive province-wide registries. Over time, it will be possible to demonstrate whether prophylactic salpingectomy is indeed associated with a reduction in the incidence of ovarian cancer. “I think this study demonstrated that there’s a lack of awareness on this issue, but also [that there’s] potential effectiveness of introducing an educational initiative like this in changing our practice patterns. As we start talking more about this issue amongst our colleagues and our patients, we’re more likely to see a practice pattern shift in the United States as well,” Dr. Findley commented.
Danish Universities prospectively document the incidence of ovarian cancer OvCa in a million postmenopausal women PMW from 1995 through 2005. Compared to non-users, use of HT increased OvCa (mean age 62yrs) by about 40% for up to 2 years after stopping Ht, ie increased the absolute incidence of clinically diagnosed OvCa from ~ 0.04 to ~0.052% ie per 100 patient yrs.
Transdermal TD ET alone increased risk by 13%; vaginal ET by 23%; Oral ET alone increased risk by 34%; oral E+ progestin Pg by 48%; TDE+Pg by 67%.
Thus the relative incidence of OvCa rose about 33% by 7 years on HT, to 48% if HT continued beyond 7years.
In 2004 Glud ea reported an increase risk of 31% for OvCa in Danish women on OHT use – total ET dose of ~5gm ie for about for 15yrs – at a time when the standard premarin dose was 0.625mg/d (equivalent to l mg E2) if not double that .
For perspective, the relative incidence of cancers in similar mostly 1st world European women from the the USA SEER data for 2006 age over 50 years are: BrCa 0.33%, uterus 0.07%, ovary o.03%(ie very similar to the baseline Danish figure of 0.04% above), colon 0.15%,and cervix 0.01%. The new (Norwegian) analysis in the latest BMJ suggests that screening mammography may result in overdiagnosis of BrCa by up to 50% (the other 50% may arguably never have been clinically significant-diagnosed- during life) , so the provocative could argue that the relative incidence of clinically significant BrCa to OvCa is more like eg BrCa 0.2 to ovary 0.03 ie just below 10:1. But OvCa is notoriously about 70% fatal within a few years, so the absolute mortality rate – at age 60-64yrs- from the same SEER source and period are as relevant: BrCa 0.063%, uterus 0.011%, ovary 0.033%, colon 0.03% & cervix 0.005%. ie new OvCa may be only 1/10th as common as newBrCa, but BrCa kills only twice as many PMW as OvCa.
And finally the 2007 survey by Rossing ea of Menopausal Hormone Therapy and Risk of Epithelial Ovarian Cancer in women in Washington State 2002-2005 showed that ET -mostly premarin (but not ET + progestin- MPA medroxyprogesterone provera) – especially in low-parity younger slim women increased OvCa compared to non-users, and that this risk was highest- up to 90%- in users of OET for more than 6 years.
By comparison – BREAST CANCER BrCa and HT: Hoover ea 1976 are the first on Pubmed to report doubling in risk of breast cancer BrCA after 15yrs on premarin in USA ie at least 5gm cumulative dose.
In Denmark by 1994 Ravn ea reported that if there was a risk of BrCa from OHT, it was small, and only after prolonged use of estrogen (15-20 years). But by 2004 -2005 Tjønneland ea , Stahlberg ea and Ewertz ea found increased risk for BrCa of 61 to 112% associated with current use of HT. Stahlberg ea already in 2003 concluded from recent studies from both the USA and Europe that the combined treatment regimens with estrogen and progestin increase the risk of BrCa beyond the risk of unopposed estrogen.
In Norway, a recent Tromso study suggested that the dominant HT therapy used in Norway was oral estradiol E2 plus the progestin norethisterone acetate. . An earlier Tromso study in only 35000 PMW was too small- it showed that use of such OHT for >5yrs trebled the incidence of breast cancer BRCa, but did not influence that of OvCa.
Apart from smokers’ lung cancer, the commonest cancer in older women- BrCa- clinically affects perhaps 5% of PMW lifelong – but with prompt therapy after clinical presentation kills as few as 5% of sufferers- and with appropriate OHT (premarin +- provera) for up to 8years in the Women’s Health Initiative both the incidence of and mortality from BrCa, and all-cause mortality, were reduced by about one-third. Hence appropriate HT saves many from both BrCa and from premature death and disability from the commonest degenerative diseases- vascular, dementing and fracturing. 75% of women who develop BrCa die with it – not from it but from far more prevalent degenerative diseases after an otherwise normal lifespan. But the Danish evidence is that combined OHT will increase OvCa by >50%.
Ovarian Ca kills 70% of victims, and is it so rare compared to BrCa? .
Hence with the perhaps 2/3 lower incidence of OvCa, it is a relatively trivial problem for women overall- except for the 4 in 10 000 women who develop it, who have <50% 5year survival, ie 3 out of 4 of whom it will kill within a few years- compared to <25% of breast cancer victims who will be killed by the BrCa.
However, it becomes clear that these hormone-dependent cancers are both duration- and total-dose HT related; but even more important, that unopposed OET is a risk if persisted more than about 12 yrs; and even if used in far lower dose parenterally, the risk of OvCa is far higher if combined with the European fashion of androgenic synthetic progestins Pg – even parenterally; whereas the American MPA for up to 8years at least apparently if anything mitigates the OvCa risk of ET..
By contrast this column has repeatedly reviewed evidence that balancing physiological ERT with physiological testosterone replacement TRT eliminates the risk for BRCA and endometrial cancer of unopposed ERT +- PRT in PMW. Intuitively this should also apply to ovarian cancer.
Hence the message strengthens that PMW should not be exposed for any length of time at any stage to the much higher oro-hepatic HT doses (needed for symptom control) or OET+- Pg; but as in all other endocrine replacement for permanent multisystem prevention – let alone sexual function- patients with gonadal deficiency should have physiological sexhormone balance restored ie with balanced parenteral human androgen, estrogen and progesterone replacement.
It is common cause that (reproductive cycles and pregnancy aside) all the physiological prime sex hormones-DHEAdehydroepiandrosterone, P4, T, E2, E3 – are as important as all other human hormones, essential life long for optimal health; and that estrogen dominance (due to inadequate androgen and progesterone levels) is deleterious. Hence most PMW require both physiological progesterone and androgen replacement- sometimes to balance excessively high endogenous estrogens, usually to accompany necessary ERT for full balance.