8 August 2019
Several international researchers complain about the fact that by making estimates of specific breast cancer mortality, the deaths resulting from heavy treatment that women undergo after cancer detection are largely underestimated. Assessing overall mortality would also allow the inclusion of deaths due to treatment.
In a synthesis, Gotsche, a former Cochrane Collaboration Investigator, an independent collective of Nordic researchers, writes :
I believe that if screening had been a drug, it would have been withdrawn from the market long ago. Many drugs are withdrawn although they benefit many patients, when serious harms are reported in rather few patients. The situation with mammography screening is the opposite: Very few, if any, will benefit, whereas many will be harmed. I therefore believe it is appropriate that a nationally appointed body in Switzerland has now recommended that mammography screening should be stopped because it is harmful.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582264/
1° Michael Baum's study :
https://www.bmj.com/content/346/bmj.f385
Harms from breast cancer screening outweigh benefits if death caused by treatment is included
Over the past 30 years, the percentage of patients undergoing chemotherapy has increased from 20% to about 80% [1]. It is obvious that chemotherapy will expose the patient to effects on her survival, her comfort of life, expose her to other morbid effects [2] [3].
Anti-hormonal treatments (anti-aromatases or Tamoxifen) can cause thromboembolic complications and myocardial infarction. A risk of secondary endometrial cancer with Tamoxifen has been noted. [4] [5] Women may experience earlier signs of menopause, arthralgia, neuropathies and cognitive dysfunction, weight gain....
Radiotherapy can cause heart and lung complications. The risk of radiogenic coronaritis increases by 7.4% per gray received by the heart and is the cause of sometimes major cardiac problems and poor prognosis. [6] [7]
But also more serious diseases such as haemopathies [8] and radiation-induced lung or oesophageal cancers. [9]
For all these reasons, Michael Baum, Professor Emeritus of Surgery, a British oncologist specialized in the treatment of breast cancer, concludes: « harms from breast cancer screening outweigh benefits if death caused by treatment is included »
2° A 1989 publication
https://www.bmj.com/content/298/6688/1611
Authors' CONCLUSIONS - Adjuvant radiotherapy after simple mastectomy for early breast cancer results in a slight excess of late mortality due to other cancers and heart disease. The risk must be weighed against the higher risk of local recurrence in the absence of immediate postoperative radiotherapy. The balance must be assessed for each patient ....
3° A disturbing Brazilian study :
https://bmjopen.bmj.com/content/7/8/e01639
We have analyzed this study here : https://cancer-rose.fr/2017/11/12/surmortalite-imputable-au-depistage-une-etude-bresilienne-troublante/
The direct association between higher breast cancer mortality and the proportion of women who use the private health sector (and use screening more often) is in line with studies on the subject published in Brazil. This counter-intuitive conclusion of increased access to health care leading to increased mortality can be explained by "over-diagnosis", but the authors also point out that wealthier women are more exposed to potential carcinogens.
According to the authors, mammography screening did not have a positive effect: rather, it was associated with an increase in breast cancer mortality.
Treatment of breast cancer has many side effects that can result from surgical complications, radiation therapy, chemotherapy and anti-estrogen therapy. The authors note that the absence of a decrease in all-cause mortality between screened and unscreened populations has been attributed to the additional risks of treatment, which are more common in screened women. The increased risks of cardiovascular disease due to cardiac toxicity from anthracycline and trastuzumab treatment and radiation therapy are well documented, and the authors also cite radiation-induced cancer due to radiation from mammography and radiation therapy.
4° Danish study of Jorgensen
https://www.ncbi.nlm.nih.gov/pubmed/20332505
https://www.bmj.com/content/340/bmj.c1241
Jorgensen k. J. Breast cancer mortality in organised mammography screening in Denmark: comparative study. BMJ. 2010;340:c1241.
The study by Karsten Jorgensen (of the Nordic Cochrane Centre) identified all cases of breast cancer deaths in Denmark from 1971 to 2006 by year, region and five-year age groups (correlated with the total female population). Breast cancers occurring in women excluded from screening (women aged 35-54 and 75 and over) were included. Mortality was observed during the ten years where screening may have had an effect.
The result is surprising because the reduction in mortality appears to be greater in unscreened areas.
Breast cancer mortality in women aged 55-74 was reduced:
- by 1% in areas where screening was available,
- by 2% in areas where it did not exist,
- of 5% in women aged 35-54 years where screening was available,
- by 6% in the same age group in areas where it did not exist.
- No change in mortality was observed in women over 75 years of age.
The reduction in mortality recorded in Denmark is therefore not related to screening, and is even more pronounced in areas where screening is not practiced.
(Indeed, in many countries where screening has been introduced, there has been some reduction in mortality since the 1990s, i.e. before the introduction of screening programs and national campaigns. Therapeutic advances are one explanation for this state of affairs, perhaps also the real prevention campaigns (move more, eat less...), the elimination of hormonal substitutes treatments).
5° A meta-analysis: Positive and negative effects on long-term survival of radiotherapy for early breast cancer: an overview of randomized trials
Published May 20, 2000 DOI: https://doi.org/10.1016/S0140-6736(00)02263-7
(by the Early Breast Cancer Trialists Collaborative Group)
Background
The long-term effects of radiation therapy on mortality from breast cancer and other causes remain uncertain.
The methods
This is a meta-analysis of the 10- and 20-year outcomes of 40 "unconfounded" randomized trials* of radiotherapy for early breast cancer. It is a review of individual patient data on recurrence and cause specific mortality in 20,000 women, half of whom were node-positive.
The areas of radiotherapy generally included not only the chest wall but also the axillary, superclavicular and internal mammary lymph nodes.
* "Unconfounded randomised trials of radiotherapy": Only trials in which comparisons are "unfounded" are included. By definition, in unconfirmed clinical trials, a group differs from the others only in the treatment of interest.
Results
A reduction of about two-thirds in the local recurrence rate was observed in all trials, largely independent of patient type or type of radiation therapy. Therefore, to assess the effects on breast cancer mortality, the results of all trials were combined.
Breast cancer mortality was reduced but mortality from other causes, particularly cardiovascular, was increased. There was little effect on early deaths, but analyses of later deaths indicate that, on average after the second year, radiotherapy reduced annual breast cancer mortality rates by 13.2% but increased those from other causes by 21.2%. Nodal status, age and decade of follow-up strongly influenced the ratio of breast cancer mortality to other mortality.
Interpretation
Radiotherapy regimen capable of producing a two-thirds reduction in the local recurrence observed in these trials, but without long-term hazard, are likely to result in an absolute increase in survival at 20 years of about 2 to 4% (except for women at particularly low risk of local recurrence).
The average risk observed in these trials, however, would reduce this 20-year survival benefit in young women and would reverse the benefit in older women.
Bibliography
[1] Spielman, Khalil, Kinetics of tumor proliferation and efficacy of adjuvant chemotherapy. Study of mitotic activity. In: Breast cancer. Proceedings of the postgraduate French-language course in oncology. pp. 455-46
http://eknygos.lsmuni.lt/springer/65/455-463.pdf
[2] Morgan g, WarD r, Barton m. The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. Clinical Oncology. 2004 Dec;16(8):549- 60. Review.
https://www.ncbi.nlm.nih.gov/pubmed/15630849
[3]Cancer Drugs Approved on the Basis of a Surrogate End Point and Subsequent Overall SurvivalAn Analysis of 5 Years of US Food and Drug Administration Approvals
Chul Kim, MD, MPH; Vinay Prasad, MD, MPH JAMA Internal Medicine. 2015 Dec;175(12):1992-4.
https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2463590
[4] Matthews A , Stanway S Long term adjuvant endocrine therapy and risk of cardiovascular disease in female breast cancer survivors: systematic review. BMJ. 2018 Oct 8;363:k3845.
https://www.ncbi.nlm.nih.gov/pubmed/30297439
[5] Fleming CA , Heneghan HM et al. Meta-analysis of the cumulative risk of endometrial malignancy and systematic review of endometrial surveillance in extended tamoxifen therapy. British Journal of Surgery. 2018 Aug;105(9):1098-1106.
https://www.ncbi.nlm.nih.gov/pubmed/29974455
[6] Junod B. Lethal side effects and radiotherapy induced cancers of breast cancer overdiagnosed in France. In Preventing Overdiagnosis Conferences. Oxford, 17 Septembre 2014. [en ligne]. http://formindep.fr/effets-indesirables-mortels-et-cancers-induits-par- radiotherapie-des-cancers-du-sein-surdiagnostiques-en-france/
[7]Sarah C. Darby, Ph.D., Marianne Ewertz et al. Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer. The New England Journal of Medicine. 2013;368:987-998.
https://www.nejm.org/doi/full/10.1056/NEJMoa1209825
[8] Martin MG , JS Welch et al. Therapy related acute myeloid leukemia in breast cancer survivors, a population-based study. Breast Cancer Research and Treatment. 2009 Dec;118(3):593-8.
https://www.ncbi.nlm.nih.gov/pubmed/19322652
[9] Bois ME , Vogel V et al. Second malignant neoplasms: assessment and strategies for risk reduction. Journal of Clinical Oncology. 2012 Oct 20;30(30):3734-45.