This case involves a 65-year-old woman who began mammograms at age 40 due to a family history of breast cancer (mother at age 80). She has already had biopsies, which revealed that she had a simple mastosis (benign condition of the breast, characterized by tension and pain in the breasts, as well as a "granular" consistency when palpating the breasts, in areas where the mammary gland is more present and dense).
A mammogram revealed two small foci of microcalcifications in one breast. A preliminary macrobiopsy was carried out, but it was unsuccessful due to difficulties in locating them. A few months later, a second macrobiopsy was performed.
The two biopsied sites revealed a carcinoma in situ (ductal carcinoma) and an "atypical hyperplasia" lesion. Due to the presence of two concomitant lesions, a complete mastectomy (complete removal) of the breast was recommended based on the pathology report.
Anatomopathology is not infallible
Breast biopsy samples can be difficult to analyze.
In a 2016 study published in the BMJ, American researchers assessed the effectiveness of 12 different strategies in reducing interpretation errors (second opinion requested for all samples, second opinion only in the case of atypia, or only in the case of the wish of the first pathologist or for first readers with less experience in breast pathology, etc...).
115 pathologists examined 240 breast biopsy specimens, one slide per case, and compared their observations to an expert consensus diagnosis.
This study revealed that pathologists who took part in the study disagreed with the expert panel's consensus about 25% of the time. Most of the disagreements were with specimens from difficult-to-interpret conditions, such as atypia, which occurs when cells appear abnormal but are not cancerous, and ductal carcinoma in situ (DCIS)
The conclusion of the study:except for invasive cancer cases where the second opinion rarely differs from the initial interpretation, ALL strategies requiring a second opinion improve diagnostic concordance and reduce misclassification rates of breast specimens from 24.7% to 18.1%, showing that variability in diagnosis is still only incompletely eliminated, especially for breast specimens with atypia.
A second opinion is thus recommended because it can mean the difference between a diagnosis of benign hyperplasia or carcinoma in situ, influencing surgical sanctions, the need for re-intervention, radiotherapy, and/or chemotherapy.
As a result, a second opinion can help patients make a therapeutic choice.
Why not propose a more systematic second reading of the biopsy?
In the case of a positive biopsy, the start of the disease is defined by this single examination of the tissue taken under the microscope (i.e., except for invasive cancer, where uncertainty is rarer) (histological diagnosis).
And it is astounding to note how, on the one hand, DCIS is considered a “stage 0” breast cancer with a very good prognosis, and how, on the other hand, the therapeutic sanctions for this DCIS and a fortiori for pre-cancerous lesions can be extremely aggressive, as aggressive as for a "true" invasive cancer.
The patient does not know the name of the person who read her biopsy; worse, she does not have the choice of the reader of her biopsy, the anatomopathologist, contrary to the choice she has for the general practitioner, the gynecologist, and even a surgeon if necessary.
This pathological anatomy report is never communicated to the patient, although it is strictly necessary and mandatory for treatment to begin. It determines the course of treatment and the therapeutic options available.
On the other hand, the pathology report is part of the patient's file and can thus be requested by the patient.
Recommendations for patients if carcinoma in situ or a borderline or atypical lesion is found.
First and foremost, don't panic; take your time. You have the following options:
1- Request that the biopsy results be sent to you physician.
2- In the event of a failure, request a complete copy of the medical file (mandatory within 8 days)
3- If you are unsuccessful, request that the Medical Council intervene to obtain it for you. You are the owner of the medical file.
4- With the result, it is legitimate to ask for a revision of the anatomopathology slides. You can even have the file re-examined by an expert (your general practitioner just has to ask for it).
5-It is also possible to ask for a second opinion from another surgeon, possibly located in another region.
The therapeutic choice can be discussed: a less aggressive intervention or even simply "careful monitoring," knowing that unfortunately in France, for the moment, very few practitioners are adept at this wait-and-see approach which is being studied in several large European trials, including the LORD trial which is still including patients.
(-Since February 2019 are also accepted CIS grade II, in addition to grade I
-Since July 2020, the randomized trial has been transformed into a patient preference trial: women have the choice of the trial arm (either surveillance or conventional treatment)
Estrogen receptor and HER2 testing has been added before patients are enrolled in the trial to rule out high-grade lesions, to provide even greater safety in the trial
-There are now 28 sites open in the Netherlands, 6 in Belgium, and 15 sites will open in other countries (France, to come!)
Conclusion
An anatomopathological diagnosis should be reviewed and discussed by caregivers, rather than being accepted as a "gold standard" because it may trigger a series of aggressive treatments, the usefulness of which should be discussed with the patient.
Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.
Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.
This graphic is based on the Cochrane meta-analysis and M. Baum's study on the consequences of screening when treatment effects are considered.
Cochrane Data
The Cochrane Collaboration (currently the Cochrane Organization) is a non-profit organization composed of volunteer researchers from all over the world who are financially independent of the pharmaceutical industry.
This collaboration aims to systematically organize scientific information and medical research data based on properly conducted clinical trials. The scientifically validated data are summarized in an accessible way and published in the Cochrane library.
To assess the screening results and weigh the benefits and risks, researchers gathered data from all previous screening studies, which included 600,000 women – both screened and not screened. They combined the findings of all studies conducted since the 1970s to compare the benefits and harms of each situation. To make their results more concrete, they projected them onto two fictitious populations of 2 000 women in the form of a "dot chart."
Each dot represents a woman. Researchers from the Cochrane Collaboration indicate overdiagnosis (red dots), false alarms (blue dots), avoidable deaths (dark dots), and deaths (black dots) to provide a comparative picture of what happens when you have a screening versus when you don't.
Michael Baum is an Emeritus Professor of Surgery, Division of Surgery and Interventional sciences, University College London, London WC1E 6BT, United Kingdom.
According to this researcher, when treatment-related deaths are included in the mortality count, the harms of breast cancer screening outweigh the benefits.
These deaths must be considered because the expected benefit of screening (the golden dot materializing the 'life saved') is outweighed by the death due to therapeutic complications (the green dot materializing the 'life shortened' by damage caused by surgery, radiotherapy, chemotherapy, and hormone therapy).
Quote from the last paragraph of the study:
"If each of those were translated into total lives saved from all causes then I would remain content but, unfortunately, when 10 000 are screened along the way about 120 to 140 cases will be overdiagnosed with the current age group invited. Four fifths of these women would receive radiotherapy and would be at an increased risk of dying of ischaemic heart disease and lung cancer. Knowing the background risks (box 2) and multiplying these by the factors 1.27 and 1.78 gives us increases of 2% for lung cancer and 1.33% for myocardial infarction. Adding that to all cause mortality rates I crudely estimate that an additional one to three deaths might be expected from other causes for every breast cancer death avoided."
Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.
Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.
Duggan C., Trapani D., Ilbawi A., Fidarova E., Laversanne M., Curigliano G. et al. National health system characteristics, breast cancer stage at diagnosis, and breast cancer mortality: a population-based analysis DOI:https://doi.org/10.1016/S1470-2045(21)00462-9
Concept of early clinical diagnosis
The authors make a distinction in their article between screening and early detection of breast cancer symptoms.
We therefore distinguish :
-Anticipated diagnosis = screening, which is based on repeated mammograms, as practiced in many countries.
- Early clinical diagnosis = the earliest possible detection of the first symptoms of breast cancer; this detection relies on the training and information of women and physicians and/or midwives (caregivers in general), on the one hand by raising their awareness (remembering to look for the symptom in the breast), and on the other hand by educating them on 'what' to look for.
- This concept of early clinical diagnosis contrasts with a late diagnosis due to the presence of symptoms of existing cancer that have been neglected for a long period due to a lack of information for women and a lack of training for caregivers.
The authors note that some countries do as well with early symptom detection as countries that use screening.
The Lancet article suggests that early diagnosis may work as well as screening.
Ukraine appears to have chosen this option, which is appropriate for developing countries that cannot afford routine mammography screening.
However, we can draw a pertinent question and a lesson from these findings for our countries where campaigns are in full swing, with mammographic screening, which no longer demonstrates its effectiveness and has drawbacks: What if early detection had a better benefit/risk ratio than routine mammographic screening?
Reducing breast cancer mortality with less overdiagnosis
The findings of the study, published in The Lancet Oncology, support the WHO recommendation, implying that early clinical diagnosis may be as effective as screening in avoiding advanced cancers and lowering mortality from breast cancer.
The benefit-risk balance of early diagnosis may be better than that of mass screening because it eliminates overdiagnosis and overtreatment caused by mammographic screening.
A serious alternative
As explained in detail on the website of Dr. Vincent Robert, statistician, this is an alternative to both screening and "doing nothing."
The idea, promoted by the WHO and confirmed by the Lancet study, is to offer this option to women to broaden their range of options and allow them to choose the path that appears to be most suitable for them, with full knowledge of the facts.
Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.
Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.
With the emergence of predictive software [1] the radiological criterion of breast density, i.e., the predominance of fibroglandular tissue over fatty tissue in the female breast, has become, despite the lack of conclusive studies, a risk factor for breast cancer on its own. Breast density is generally high in young, non-menopausal women (but may persist after menopause), in leaner women with low body fat, and in women undergoing hormone replacement therapy during menopause.
As we said, it is a radiological criterion; whether this characteristic is really associated with an increased risk of cancer, opinions diverge and the question is far from being decided in the course of studies, which does not prevent opinion leaders from raising the scarecrow of dense breasts to terrorize women, if need be....[2]
What is established, however, is that with high breast density the discriminating power of mammography and the ability of the radiologist's eye to detect a lesion are greatly diminished, and it is only a short step from there to make a shortcut between breast density and cancer risk.
Available studies
Several studies are available, starting with the Wolfe study [3] on the relationship between breast density and breast cancer risk. This old study was strongly contested at the time, even by the supporters of screening.
Other studies have since been published, studying the relevance of linking this density factor with other risk factors, in order to develop models for calculating the risk of contracting breast cancer within 5 years. [4] [5] [6] [7] [8] [9] [10]
Today, there is no convincing evidence that high breast density is associated with risk of death from breast cancer. Today, no tool for estimating the risk of breast cancer using breast density has yet proven its relevance.
The HAS(Higher Authority for Health in France), in a work on the identification of risk factors, writes:
"High pre-menopausal breast density was not retained as a risk factor at the end of the work of part 1."[11]
The viewpoint published in JAMA on May 9, 2019[12]
The background is the adoption by the US Congress of legislation on breast density.[13]
More precisely this legislation requires the US Food and Drug Administration (FDA)[14] as part of the regulatory process to ensure that all mammography reports and summaries provided to patients include information on women' s breast density. This authority, which oversees the regulation of mammography facilities and quality standards, has previously required the reporting of breast density in radiologists' reports.
Based on published studies (see our bibliography), and according to the authors of this viewpoint published in JAMA, breast density as a risk factor for developing breast cancer draws attention to the fact that the associated increase in cancer risk is modest, and that for women diagnosed with breast cancer, increased breast density was not associated with an increased risk of poor-prognosis cancer or death from breast cancer.
Dense breasts are common (43% of women aged 40 to 74 years) and the majority of women with dense breasts will not develop breast cancer....
According to the editors of this article, notification of breast density may increase confusion and anxiety related to mammography and breast cancer, without providing clear recommendations on what women with dense breasts should do.
The USPSTF [15], in 2016, concluded that there was insufficient evidence to recommend additional breast imaging in women with dense breasts. This group raises several points of concern with this legislation requiring notification of breast density information to women.
Significant variability and limited reproducibility in the determination of dense breasts. This variability exists on an examination whether it is read by one radiologist or by different radiologists. The exam for a given patient may have different classifications and lead to misunderstandings leading to a reduction in a woman's confidence in screening in general, and confusion about her own breast cancer risk.
Uncertainty about initiatives undertaken by women who have been notified of significant breast density to reduce their risk of dying from breast cancer. This refers to the request for additional tests for which there is no evidence to support the indication, as there is no evidence that the addition of imaging other than mammography in women with dense breasts will reduce cancer mortality; instead, these additions increase false positives, unnecessary biopsies, and overdiagnosis. The recall rate is significantly increased by the addition of ultrasound (by 14%), and by the addition of MRI (from 9 to 23%) with low PPVs[16] and an obvious additional cost. The authors remind us that MRI, often considered to be harmless, is likely to have a (small) excess risk of nephrogenic systemic fibrosis, and uncertain risks of gadolinium deposition in the brain when the examinations are repeated. Tomosynthesis (TS) is mentioned as an additional technique used, but the authors point out that longer-term studies are needed to determine whether the routine use of TS in women with dense breasts leads to a real improvement in breast cancer outcomes (mortality, decrease in the rate of serious cancers).
Difficulty in communicating information about breast density to patients. Experts consider this communication difficult and dependent on the literacy level of the population. Study results show poor understanding and confusion and misinformation of patients when information about breast density is given.
Impact Analysis of FDA[17]
In this analysis the FDA claims that mandating breast density reporting would reduce breast cancer mortality in women, as well as costs through early detection of cancers .... But the authors of the viewpoint point to a troubling lack of evidence to support this arbitrary conclusion.
The FDA analysis failed to include in its calculation the costs associated with overdiagnosis, with overtreatment due to additional tests, and the costs of additional visits to primary care physicians.
In conclusion
The authors believe that breast density notification has implications for public health and that physicians, researchers, public health experts, and organizations should take a stand against this imposed rule.
Breast density notification could give clinicians and patients the opportunity to discuss a particular woman's risk of breast cancer, which depends on many factors other than breast density.
Predictive models of breast cancer risk include breast density, but its addition improves predictive estimates little. The addition of complementary imaging should be limited to high-risk women based on other risk factors to be included than breast density alone.
Discussions about the potential benefit of additional imaging for dense breasts should focus on the lack of evidence for a reduction in breast cancer deaths, and the well-known increase in false positives, unnecessary biopsies, and increased health care costs, as well as increased overdiagnosis and overtreatment.
In particular, when deciding on annual surveillance for high-risk women, these elements should be taken into consideration.
Clinicians should also engage patients in discussions about the importance of lifestyle (limiting alcohol, avoiding obesity, regular exercise) to reduce breast cancer risk.
Research will be needed to improve the coherence of reports on breast density and the quality of communication.
Additional research will also be essential to judge the long-term outcomes of complementary imaging to determine whether the benefits outweigh the harms.
But the authors point out that such studies will be increasingly difficult to conduct if the use of complementary imaging is routinely incorporated into screening mammography in women with dense breasts, which is currently the case (Editor's note).
"Mammographic screening should be individualized based on a woman's age, breast density, history of breast biopsy, family history of breast cancer, and knowledge regarding the benefits and harms of screening."
The Contributions of Breast Density and Common Genetic Variation to Breast Cancer Risk Article (PDF Available) in JNCI Journal of the National Cancer Institute 107(5) · May 2015 with 77 Reads DOI: 10.1093/jnci/dju397 · Source: PubMed Celine M Vachon
[6] McCormack VA, dos Santos Silva I. Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2006;15(6):1159–1169 https://www.ncbi.nlm.nih.gov/pubmed/16775176
[7] KERlikowske K, Cook AJ, Buist DS, et al. Breast cancer risk by breast density, menopause, and postmenopausal hormone therapy use. J Clin Oncol. 2010;28(24):3830–3837. https://www.ncbi.nlm.nih.gov/pubmed/20644098
Breast Cancer Research and Treatment May 2012, Volume 133, Issue 1, pp 1–10| Cite as
Risk prediction models of breast cancer: a systematic review of model performances Thunyarat Anothaisintawee, Yot Teerawattananon, Chollathip Wiratkapun
"Most (risk prediction) models have produced relatively low discrimination in internal and external validations. This low discriminative accuracy of existing models may be due to a lack of knowledge of risk factors, heterogeneous subtypes of breast cancer, and different distributions of risk factors among populations."
[9] McCarthy AM, WE Barlow, Conant EF, et al; Consortium PROSPR. Cancer du sein de mauvais pronostic diagnostiqué après mammographie de dépistage avec résultats négatifs. JAMA Oncol . 2018; 4 (7): 998-1001. doi: 10.1001 / jamaoncol.2018.0352
"Breast density has received much attention as a primary factor identifying the need for additional screening, but it may be more effective to consider both breast density and age to identify women at risk for poor prognosis breast cancer."
[10] Gierach GL, Ichikawa L, Kerlikowske K, et al. Relation entre la densité mammographique et la mortalité par cancer du sein dans le Consortium de surveillance du cancer du sein. J Natl Cancer Inst . 2012; 104 (16): 1218-1227. doi: 10.1093 / jnci / djs327
"High mammographic breast density was not associated with risk of death from breast cancer or any cause after controlling for other patient and tumor characteristics. Thus, risk factors for breast cancer development may not necessarily be the same as factors influencing risk of death after breast cancer development."
[14] The Food and Drug Administration is the U.S. Food and Drug Administration.
[15] Melnikow J, JJ Fenton, Whitlock EP, et al. Supplemental breast cancer screening for women with dense breasts: a systematic review for the US Preventive Services Task Force.
(USPSTF, United States Preventive Services Task Force is an independent U.S. preventive services task force of primary care and prevention experts that systematically reviews evidence of effectiveness and develops recommendations for clinical preventive services).
16] Positive predictive value, which is the likelihood that the subject actually has cancer when he or she has a positive test.
[17] Office of Policy, Planning, Legislation and Analysis, Office of the Commissioner, Food and Drug Administration. Mammography Quality Standards Act; Amendments to Part 900 Regulations: File No. FDA-2013-N-0134.
Mammography Quality Standards Act; Amendments to Part 900 Regulations (Proposed Rule) Regulatory Impact Analysis
Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.
Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.
Effect of screening by clinical breast examination on breast cancer incidence and mortality after 20 years: prospective, cluster randomised controlled trial in Mumbai
- Contribution of Dr M.Gourmelon for the decoding the presentation of the risks of mortality. Appendix b
- Contribution of Dr V.Robert for the statistical analysis. Appendix c
27/02/2021
Three randomized controlled trials were conducted in Russia, China and the United Kingdom [appendix a] involving a total of almost 400,000 women, which showed neither a decrease in breast cancer mortality nor a decrease in mastectomies. On the other hand, false positives were increased, leading to additional examinations and biopsies with normal results, and they also caused an increase in women's anxiety.
There was also a question of screening by trained professionals, the problem being the reproducibility from one practitioner to another which is not good. In short, clinical breast examination as a routine screening method has not been retained, as breast self-examination does not ultimately prove to be an effective method for the early detection of breast cancer. And it is still unclear whether screening by clinical breast examination can actually reduce breast cancer mortality
An Indian trial
A new study using the idea of clinical breast examination as mass screening is being conducted by a team of researchers in Mumbai, who are publishing the results of their 20-year randomized controlled trial.
The objective of the study was to test the effectiveness of breast cancer screening by clinical examination in reducing mortality from the disease and also in reducing the stage of cancer at diagnosis, compared with no screening.
151,538 women aged 35 to 64 years with no history of breast cancer participated in the study. Women in the screening group (75,360) received four rounds of clinical breast examination screening (performed by trained primary care professionals) and cancer awareness information every two years. Women in the control group (76,178) received information on cancer awareness and eight rounds of active surveillance every two years.
It is examined whether, in the screening group, the cancer found is of a lower stage at the time of diagnosis compared with unscreened women, and of course whether mortality from the disease has decreased.
The main results of the study are as follows:
-Clinical breast examination performed every two years by primary care professionals significantly reduced the stage of breast cancer at diagnosis. -Clinical breast examination led to a non-significant 15% reduction in overall breast cancer mortality; BUT this is a relative reduction, i.e., for the screened group compared to the unscreened group (control group). See: [appendix b] -The authors conclude that there was a significant reduction of nearly 30% in mortality in women aged ≥ 50 years. BUT This is a subset analysis done post hoc, not provided for in the original study protocol, so after the data were known; again, this is not an absolute reduction but a relative reduction in risk by comparing two groups. See: [appendix b] -No significant reduction in mortality was observed in women under 50.
From the authors' perspective, what the Mumbai trial provides:
-In this 20-year study, clinical breast examination by trained health workers in Mumbai led to a reduction in breast cancer at diagnosis and a reduction in mortality from the disease by nearly 30% in women aged 50 years and older, but with no reduction in mortality observed in the group of women under 50 years. -A 5% reduction in all-cause mortality was observed in the screening arm compared with the control arm, but this was not statistically significant. -Clinical breast examination should be considered for breast cancer screening in low- and middle-income countries.
Review of the Study for Robustness
We present here the analysis of Dr. Robert, statistician of the Cancer Rose group, which you will find more exhaustively in the appendix at the end of the article [Appendix c].
In his opinion, the post-hoc analyses [1], which are included in the abstract and in the conclusion, are problematic.
We summarize his main conclusions about the study:
1-Post-hoc analyses raise suspicions of either a lack of scientific rigor or a lack of objectivity, with a propensity to want to demonstrate a posteriori, by an analysis not previously foreseen in the study protocol and made on the basis of the available data, at any price the effectiveness of screening by clinical breast examination.
2-The study is presented as randomized but in fact it is a cluster randomization (by groups of individuals and not by individuals). The authors do not give any information on the size of the clusters, nor on their characteristics. It is therefore impossible to know whether or not the randomization is sufficient to make the 'screened' and 'control' groups comparable.
3-The manner in which deaths are attributed (cause of death by breast cancer or other cause?) is debatable. When two physicians consulted to determine the cause are unanimous, the cause is retained, but if there is a disagreement a third opinion is required and the majority of opinions prevail; a rigorous process would require eliminating the disputed case.
Other remarks
Of course, there is a certain rate of over-diagnosis which dilutes the number of more advanced cancers in the total number of cancers found. This means that, as the results are expressed as a percentage, one has the impression that there are more cancers of an earlier stage in the screened group. It is surprising that the BMJ accepts this presentation in percentages which biases the results. And indeed, there are overall more women with breast cancer in the screening arm (198) than in the control arm (151).
(It is known that the presentation in percentages embellishes the data and gives a fictitious perception of reality.)
Thus, in Appendix 4 of the report of the citizens' consultation [Appendix d] (page 155) for example, since the citizens had asked for an honest rendering of the data, graphic representations are proposed of what the percentages represent "in real life").
The main point is that the overall result is not enthusiastic, since there is no statistically significant decrease in breast cancer mortality in the screened population as a whole. And it is always problematic, as Dr Robert points out, to have the results of analyses carried out afterwards, once all the data are in hand, allowing one to "choose" what one wishes to put forward, thus leaving doubt as to the admissibility of the results.
Bernard Duperray[2], in his book "Breast Cancer Screening, the Great Illusion", mentions the Shanghai study where the results found are almost opposite to those of the Mumbai trial: "In a trial carried out in Shanghai from October 1989 to October 1991 on nearly 270,000 women, 130,000 were trained in breast self-examination under medical supervision and compared with a control group (not screened). Cumulative breast cancer mortality rates after 10 to 11 years of follow-up were similar in both groups ...... [3].
To conclude
It is important to keep in mind that this study took place in a very different setting than our Western populations. Initiatives to clinically examine women breast by trained personnel in a setting like Mumbai are likely to reduce the morbidity and stage of cancers for which women may be arriving too late for care. The authors describe the difficulties[4] encountered in carrying out this trial, particularly from the point of view of financing, when Europe at the same time is capable of sacrificing 12 million euros for a study that failed before it even began, and which will not provide any usable information either on overdiagnosis or on the usefulness of mammographic screening.[5]
If this article lacks scientific robustness, and the interest of organized screening by clinical breast examination cannot be formally affirmed, the non-interest of this type of screening by clinical examination is not demonstrated either! A more robust three-arm trial could be imagined, with a 'no screening' arm.
A 'rapid response' to the publication of this study[6] (Ismail Jatoi-Professor and Chief, Division of Surgical Oncology and Endocrine Surgery-University of Texas Health Science Center, San Antonio) is quoted here: ".... the risk of overdiagnosis will increase with the use of more modern screening technology (i.e., tomosynthesis, magnetic resonance imaging), which increases the rate of detection of more occult (non palpable) cancers."
... "Taken together, the results of the Mumbai trial and the CNBSS[7] suggest that a clinical trial randomizing women aged 50 years and older to mammography screening versus clinical breast examination (CBE) screening is now warranted. If such a trial demonstrates that there is no additional benefit to mammography screening beyond what is achievable with CBE screening, then CBE screening should replace screening mammography as the optimal method of breast cancer screening."
Ethically, a randomized clinical trial testing mammographic screening versus clinical screening would be justified, but in France it is unfortunately not possible, since the argument often put forward is that it is unethical to exclude women from mammographic screening. It seems to be considered more ethical to coercively and insistently call women to a radiological screening that has failed....
But the pandemic and future problems of health resource allocation may lead us to rethink this kind of testing around the world, especially for underprivileged populations, rather than furthering disappointing mammographic screening with technologies we know in the western world, which increasingly leads to overdiagnosis.
References
[1] In a scientific study, post hoc analysis (from the Latin post hoc, "after this") consists of statistical analyses that have been specified after the data have been accessed. This usually creates a multiple testing problem because each potential analysis is in fact a statistical test. Multiple testing procedures are sometimes used to compensate, but this is often difficult or impossible to do accurately. Post-hoc analysis that is conducted and interpreted without adequate consideration of this problem is sometimes called "data dredging" by critics because the statistical associations it finds are often wrong. (Wikipédia : https://en.wikipedia.org/wiki/Post_hoc_analysis )
[2] Bernard Duperray "dépistage du cancer du sein, la grande illusion"-éditions Thierry Souccar.
[3] THomas DB, gao Dl et al. Randomized trial of breast self-examination in Shanghai: nal results. Journal of the National Cancer Institute. 2002 Oct 2;94(19):1445-57.
Cox B. Variation in the effectiveness of breast screening by year of follow-up. Journal of the National Cancer Institute. Monographs. 1997;(22):69-72.
Retsky m. New concepts in breast cancer emerge from analyzing clinical data using numerical algorithms. International Journal of Environmental Research and Public Health. 2009 Jan;6(1):329-48.
[7] Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ. 2014;348:g366.
b] Explanation of the misleading nature of risk presentations in terms of relative percentage reduction in risk of death. Dr M. Gourmelon
1-Clinical breast examination led to a non-significant 15% reduction in overall breast cancer mortality-
The 15% comes from the following relative calculation:
breast cancer mortality in the screening group 213 deaths, 251 in the control group.
251 -213 = 38
3800/251 = 15,13 %
This is how we obtain a 15% relative reduction in breast cancer mortality.
But what is it in absolute terms?
213 deaths for 75360 women in the screening group.
21300/75360 = 0.2826% is therefore the absolute percentage of deaths of women from breast cancer in the screening group
251 deaths for 76178 women in the control group.
25100/76178 = 0.3295% is the absolute percentage of women who died of breast cancer in the control group.
We therefore have: 0.3295 - 0.2826 = 0.0469% rounded to 0.05% fewer women deaths.
The relative percentage is therefore 15%, and the absolute percentage is 0.05%.
The absolute percentage represents the reduction in mortality of women between the screening group and the control group.
The relative percentage expresses the difference between the total number of deaths in the screening group and the control group, a reduction for a group not for individuals.
However, what is important to know for good information for women is the reduction that they can expect from screening and not how much of a reduction screening brings in the screening group compared to the non-screening group.
But to "promote" screening, it is better to put forward a figure of 15% reduction, which does not concern women directly but which they will interpret as such, than 0.05%, which is the real reduction they can expect by undergoing screening.
This is all the subtlety of presentation of the figures that most readers of the studies will not be aware of, but that the authors, yes. And that the French citizen consultation of 2015 had asked that such presentations are no longer accepted.
2-Second in the same way:
The authors conclude that there is a significant reduction of almost 30% in mortality in women aged ≥ 50 years.
The 30% comes from the following calculation, in the same way:
64 women over 50 years of age who died of breast cancer in the screening group, 93 in the control group.
There is therefore a reduction in breast cancer deaths of : 93-64 = 29
so 2900/93 = 31.18% relative reduction in mortality in women over 50.
But what about the absolute reduction:
64 women died out of 20965 women over 50 in the screening group.
6400/20965 = 0.3053% absolute breast cancer mortality in the screening group
93 women died out of 21909 women over 50 in the control group
9300/21909 = 0,4245 %
or 0.4245-0.3053 = 0.1192
Therefore, in absolute terms, the reduction in mortality of women from breast cancer is 0.12%.
In the same way as before, calculating in absolute % expresses the mortality risk of women over 50 and therefore its reduction, whereas on the other hand, the relative % only expresses a reduction of one group in relation to another: the comparison between the group of screened women and the group of unscreened women and in no case the reduction of risk of women over 50 themselves.
3-Finally, the same is applicable:
A 5% reduction in all-cause mortality was observed in the screening arm compared with the control arm, but was not statistically significant :
11853 all-cause deaths in the control arm
11261 all-cause deaths in the screening arm
11853-11261= 592 fewer deaths.
59200/11853= 4.9945% so 5% fewer deaths between the screening group and the control group but not 5% fewer women who died, because for that you have to calculate in absolute percentage.
This gives:
1126100/75360= 14.94 %
1185300/76178= 15.56 %
15,56-14,94 = 0.62 %
c] Dr Robert's analysis
1. With each post hoc analysis (each subgroup comparison), we give ourselves an additional chance of arriving at a statistically significant result by chance.
Thus, to arrive almost certainly at a statistically significant result, it would be sufficient to create the subgroups at random 100x in a row. With the usual significance level of 0.05, there would be a little more than 99 chances out of 100 that at least 1 of the 100 subgroup comparisons would give (by chance, since the subgroups were formed on a random basis) a p.value <0.05 (in other words, a statistically significant result). (Editor's note: Thus we keep this analysis which seems positive according to the criteria retained by the authors and we can ignore the other 99 studies which appear negative).
Thus the authors do not report 100 post hoc analyses but only 2 (one for the under 50s and one for the over 50s). But, with the 2 post hoc analyses + the main analysis (the one without subgroups), this still gives 3 "tickets" to try to have at least one statistically significant result. The risk of error in the conclusion is therefore no longer 0.05 but about 0.143.
More importantly, it is not known how many post hoc analyses were actually performed. The authors show results for subgroups under 50 and over 50. But in fact, we don't know how many subgroups they tried before arriving at a subgroup with a statistically significant result. Nothing says that they didn't try more than 36 years: no success; then more than 37 years: no success; then more than 38 years: no success; ...; then more than 50 years: p.value = 0.02 we can publish.
The problem is that, in doing so, they would have given themselves 15 "tickets" to have a statistically significant result. The risk of error in the conclusion would therefore no longer be 0.05 but 0.537 (in other words, more than a 1 in 2 chance that the conclusion of a decrease in mortality in women over 50 years of age is due to chance and questionable statistical methodology).
The fact that the authors did post-hoc analyses (no matter how many) proves : - a lack of statistical rigor or knowledge - a lack of objectivity with a strong desire to demonstrate at all costs the effectiveness of screening by palpation (and from then on, one has the right to question the honesty of the study).
2. The study is presented as randomized but in fact it is a cluster randomization (by groups of individuals and not by individuals). The authors state that there are 20 clusters but give no information on the size of the clusters and the heterogeneity of risk factors between the different clusters. It is therefore impossible to know whether or not randomization is sufficient to make the screened and control groups comparable.
To understand the importance of the problem, let's take a caricatured situation:
2 clusters, one high-risk, the other low-risk. In this situation, randomization does not change the comparability of the groups. One will receive the high risk cluster and the other the low risk cluster. Randomization or not, the 2 groups will not be comparable. If the clusters are perfectly identical in terms of risk factors, randomization is unnecessary. No matter how the clusters are assigned to each group, there will be no problem of comparability anyway since all clusters are identical in terms of risk factors. If there are an infinite number of clusters, it does not matter whether they are identical or not in terms of risk, the randomization will balance the distribution of the high and low risk clusters between the 2 groups.
In practice, we are always in an intermediate situation, with a number of clusters > 2 but not infinite and clusters that are not perfectly identical in terms of risk. In order to judge whether or not cluster randomization is likely to produce comparable groups, it is therefore necessary to know both the number of clusters and the heterogeneity between clusters.
3. The way to decide whether or not a death is attributable to breast cancer is rather curious.
Two doctors give their opinion. If the two opinions converge, these identical opinions determine the attribution (OK with that).
If the two opinions differ, a 3rd opinion is requested and the majority opinion determines the attribution. And there is a problem. The majority decision is democratic and well adapted to politics but it is not scientific. If the opinions of the first two doctors differ, the situation is ambiguous.
And it would be more honest not to take these cases into consideration than to want to remove the ambiguity at all costs by a 3rd opinion not necessarily more reliable than the first two.
It is difficult to know how many cases of disagreement there were. There were 17% in one group and 10% in the other where the cause of death could not be attributed; but figures on the frequency of cases where the attribution was made despite a contrary opinion from at least one of the physicians cannot be found. This is crucial information.
At the very least, the robustness of the conclusions should have been checked by a sensitivity study taking into account non-attributions and ambiguities in the attribution of the cause of death (curiously, this was done for the analysis of the staging (analysis of the stage of the cancer at the time of its diagnosis) of cancers and not for the analysis of cancer deaths; in the case of deaths, this removes all reliability from the conclusions)
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Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.
In the Journal of The National Institute Volume 113, Number 1, January 2021, is published an article of 2020 on an important meta-analysis. It discusses the contribution of digital mammography in breast cancer screening, a publication that we had relayed here: https://cancer-rose.fr/2020/06/28/la-mammographie-numerique-pas-plus-efficace-dans-la-reduction-des-cancers-les-plus-graves-selon-meta-analyse-australienne/
Digital mammography, approved in 2000 by the American FDA, is also widely used in France.
Studies suggested that the new technology is equivalent to the old analog film technology for cancer detection.
A short technical description
Analog mammography produces an image printed directly on silver film.
Digital sensor radiography (CR), which has now completely replaced the analog one, is an indirect mammography technique that captures the image on a reusable plate. This receptor of image contains a photostimulated luminophore, the X-rays cause an excitation of luminescent molecules which convert the X-rays to light. An analog-to-digital converter then produces a digital image that can be archived.
Direct Digital Radiography (DR) does not use reusable plates. Sensors convert the X-ray stream directly into an electrical signal which is then digitized and transferred to the screen. The image is visible and can be analyzed on the screen directly by the radiologist. The image can then be enhanced if it is over or underexposed for a better visualization. In this case too, the images can be stored as digital files in a computerized archiving system.
The article
In the article published in the National Institute's journal, authors Otis W Brawley (oncologist and epidemiologist in Baltimore, USA) and Channing J Paller (oncologist and urologist in Baltimore, USA) first recall the results of this important meta-analysis.
Digital mammography is certainly justified by easier storage and handling of images. There is also a possibility of computer-assisted diagnosis and better performance for the exploration of dense breasts. Digital mammography also has a lower radiation exposure than film mammography, provided that the number of images is not increased unreasonably... More on this later.
For effective screening, the authors point out, three objectives must be met: more localized tumors found at the same time as a decrease in interval cancers (tumors diagnosed between two screenings), and a decrease in the incidence of advanced cancers.
Regrettably, the Australian meta-analysis by Faber et al. (Sydney School of Public Health, Australia) confirms the problem of increased overdiagnosis with this method, which allows more detection of small lesions, particularly carcinomas in situ, the vast majority of which do not affect the life of the woman diagnosed, but there is no difference in the detection rate of invasive cancers.
The study suggests that 11% of cancers detected by digital mammography are overdiagnosed. However, other analyses cited in the article are much more pessimistic about the rate of overdiagnosis attributable to the digital system [1].
The digital technique also has no effect on interval cancers, which are not reduced.
In the United States, the age-adjusted incidence rate (new diagnoses) of breast cancer increased by more than 30% from 1975 to 2000, while the incidence of advanced breast cancer at the time of diagnosis was stable for the 25 years, instead of decreasing as expected.[2]
Most importantly, the recall rate is significantly increased with digital technology because of the increase in false positives, which means that the claim of less radiation with digital technology is questionable, since these women recalled because of false suspicion of cancer will undergo, among other examinations, new X-rays.
Highlights from the article
Two interesting points are made by Brawley and Channing in relation to the results that can be extracted from the Australian meta-analysis:
1. The true measure of the value of effective screening at the population level is a reduction in cancer mortality and unnecessary treatment.
Screening should not justify its apparent success on the discovery of more and more cancers, many of which are unnecessary detections, but rather on the detection of more cancers that are important to find because they are clinically dangerous to the women who develop them. But digital mammography is not more discriminating for these forms and overdetects a large number of cancers that would not have caused any consequence.
2. It is human nature to think that the new technology is always the best, and many experts felt that digital mammography would lead to better health outcomes.
Sometimes we have to face the fact that the truth is different from what experts have put forward. These results demonstrate, according to the authors, the importance of post-marketing evaluation and open-mindedness.
These results also show the biological variations of breast cancer, and confirm a non-linear natural history of the pathology: some cancers are useless to find because they regress or do not progress, others are immediately aggressive and develop between two screening mammograms without any possibility of stopping their occurrence.
Our commentary
We invite our readers to read the work of Bernard Junod and Dr Bernard Duperray on overdiagnosis. The natural history of cancer is of paramount importance, without this knowledge we will never be able to understand the problem of overdiagnosis and interval cancers.
[2]Welch HG, Gorski DH, Albertsen PC. Trends in metastatic breast and prostate cancer–lessons in cancer dynamics. N Engl J Med. 2015;373(18):1685–1687.
Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.
Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.
This "researchers' letter" is from Australian scientists including Prof. A. Barratt, Professor of Public Health at the University of Sydney and Dr. Ray Moynihan, Australian researcher at Bond University and health journalist, focuses on the media coverage of screening tests. It was published in JAMA on April 5, 2021. The authors of the publication study the way in which the balance of benefits and harms of 5 tests are treated in the media.
Media is key to promoting testing of asymptomatic individuals in the population, and might play an important role in encouraging realistic reporting of the benefits and harms of screening, including unnecessary diagnoses.
But data suggest that medical media coverage tends to exaggerate benefits, minimize harms, and ignore conflicts of interest.
Methods
The authors studied all English-language narratives from 2016 to 2019 in LexisNexis (a publishing and professional information company), ProQuest (a global company providing tools for content search and management from dissertations, theses, books, newspapers, periodicals, etc.) and Google News.
All types of non-fiction articles from newspapers, blogs, magazines, and broadcast transcripts were included as long as they mentioned or implied benefit or harm from medical testing, with or without disclosure of conflicts of interest of the narrators involved.
The stories were reviewed for health benefits (early treatment, saving lives) and harms (false positives, overdiagnosis), and reflected views expressed by the commentators according to their agreement or disagreement.
Five early detection tests were targeted by this review: liquid biopsies, tomosynthesis also known as three-dimensional mammography (discussed on this site [1] [2]), electrocardiogram recording using the Apple Watch Series4 app, blood biomarkers for dementia, and artificial intelligence technology in dementia.
Results
Overall, media coverage focuses much more on the benefits of early detection testing than on the harms, and the risk of overdiagnosis was poorly covered.
Overall, 97% of the narratives reported benefits, 37% reported harms, and only 34% reported both benefits and harms.
63% of stories reported only benefits, while only 3% reported only harms.
Overdiagnosis was mentioned in only 57 of the 432 stories, making only 13% of all content that mentioned harms, or 5% of stories in the entire set.
In total
This study confirms the results of other similar studies on the subject of health media coverage[3] [4] [5].
The authors suggest that improved media communication would encourage a healthier skepticism about the health options available to populations, and reduce the problem of overdiagnosis (or overdetection).
They argue that strategies are urgently needed to improve media coverage so that professionals, patients and the public receive more balanced information about early detection tests.
Comments
In the past, we have repeatedly expressed our alarm at the biased reporting of scientific facts in the media.
In the case of screening mammography, easy slogans are used, facilitated by the impossibility for women to make an informed decision since they are fallaciously informed, as shown in a previous study[6].
A commentary published following the Australian study in JAMA was of particular interest to us[7]. It is that of Dr. Diamandis[8], head biochemist of the University Health Network and 'Toronto Medical Laboratories' and also division head of clinical biochemistry in the department of pathobiology at the University of Toronto in Ontario, Canada.
Indeed, we can remember the unbridled media hype and enthusiasm, as early as 2015, about "liquid biopsies"[9]. The "woman who would beat cancer", "the heroine of modern times" was presented on many television platforms and several more or less glamorous media. She was Mrs. Patrizia Paterlini-Bréchot, a scientist who worked on the development of liquid biopsies. [10][11] [12] [13] [14] [15] [16] [17]
But studies and publications that are less media-friendly[18] [19] dampen this enthusiasm about the possibility of using liquid biopsies more widely as routine population-based screening. Indeed, in addition to its high cost and complexity, these tests on circulating tumor DNA seem to suffer from the same problems of low sensitivity and specificity as traditional biomarkers if we try to use them for screening in an asymptomatic and a priori healthy population. This means that we are heading for over-diagnosis, large numbers of false positives, with panic in the population and cascades of additional examinations for those who test positive (for a better understanding of these notions, see here: https://cancer-rose.fr/2016/11/13/cancer-du-sein-un-peu-de-technique/).
In his commentary to the Australian team's study, Dr. Diamandis writes:
"More recently, as the authors pointed out, we have seen a strong push by academic researchers and companies for DNA tests of circulating tumors for early cancer detection. However, our calculations showed that this test will only be able to detect large symptomatic tumors. We further stressed the need for newspapers to provide a space for healthy debate on such controversial issues. Since: biased reporting favoring the good news, but not the bad news..."
[3] MoynihanR,BeroL,Ross-DegnanD,etal.Coveragebythenewsmediaof the benefits and risks of medications. N Engl J Med. 2000;342(22):1645-1650.
[4] MoynihanRN,ClarkJ,AlbarqouniL.Mediacoverageofthebenefitsand harms of the 2017 expanded definition of high blood pressure. JAMA Intern Med. 2019;179(2):272-273.
[5] Walsh-ChildersK,BraddockJ,RabazaC,SchwitzerG.Onestepforward,one step back: changes in news coverage of medical interventions. Health Commun. 2018;33(2):174-187.
[9]Liquid biopsy consists, schematically, in taking a blood sample to detect as early as possible material released into the blood by cancerous tumors. Three tools can be used: detection of circulating tumor DNA, circulating tumor RNA, circulating tumor cells.
For the moment, this is considered to be an interesting avenue for research. But a person who does not have cancer and is simply concerned about his or her health cannot, today, benefit from this type of blood test.
[18] Fiala C, Diamandis EP. Utility of circulating tumor DNA in cancer diagnostics with emphasis on early detection. BMC Med. 2018 Oct 2;16(1):166. doi: 10.1186/s12916-018-1157-9. PMID: 30285732; PMCID: PMC6167864.
"The use of CTCs or tcDNA as tools for early detection of primary tumor or recurrence remains a very active area of clinical research, but is not, in the absence of clinical evidence, routinely applicable."
Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.
Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.
Summary Dr C.Bour, with the help of our referent patient Sophie
Under this title the authors aim to analyze how health authorities can subtly influence citizens to participate in cancer screening programs. The researchers identified and analyzed several "categories of influence", i.e. several methods of pushing the public to undergo screenings. They point out that when influences become too severe, this is at the expense of citizens' ability to make a personal choice.
Methods of study
Two methods were chosen:
A systematic literature search was performed on three databases listing scientific articles and publications which are: PubMed, Embase and PsycINFO. In addition, a review of the so-called "grey" literature was carried out, i.e. information brochures and website content from regulatory authorities and patient organizations targeting general public.
Relevant experts were contacted via international email lists and asked to provide examples of systematic influences in cancer screening. These experts are members of independent groups and have expertise in cancer and the collateral damage of screening.
These include the following groups: EuroPrev (18 members),[1] Nordic Risk Group (24 members),[2] Preventing Overdiagnosis (27 members),[3] a Google group (breast-cancer-screening google group) with a special interest in screening mammography (42 members), and Wiser Healthcare (21 members).
Results
From the 19 articles included and the expert survey, six main categories of systematic influence were identified: (a) misleading presentation of statistics, (b) misrepresentation of harms versus benefits, (c) opt-out, (which consists in considering as passive consent the fact that a solicited patient does not object to the invitation to screen), (d) recommendation of participation, (e) fear appeals, (f) influence on general practitioners and other healthcare professionals.
The authors provide examples for each category.
a) Misleading presentation of statistics
This involves presenting mortality reduction data in an embellished way by using percentages of relative reduction in the risk of dying, instead of raw figures.
Editor’s note : For example, in the case of breast cancer screening, a mortality reduction of 20% is presented. This is a reduction in the risk of dying when comparing two groups, i.e. one group against another. With this kind of presentation, one might think that 20 out of 100 people screened would die of cancer. This is not the case, explanation: If out of 1000 screened women 4 die of breast cancer, and out of a group of unscreened women 5 die of breast cancer, the passage from 5 to 4 constitutes mathematically a reduction of 20% of mortality, but in absolute figures it only makes a difference of one woman... This is why it is important to always require a presentation in real data, and not in percentages, which embellishes the situation.
Often physicians and patients have a limited understanding of the statistics, and exposing risk reductions in relative numbers is likely to increase participation especially because citizens overrate the benefits of screening.[5]
b) Misrepresentation of harm compared to benefits:
This method of influence can be applied by presenting the benefits in relative figures, as we have just seen, and the harms in absolute figures. Alternatively, certain types of harms can be minimized and even omitted altogether.
The authors cite as an example a British information brochure on mammography screening in which the reduction in breast cancer mortality was emphasized, but a major harm such as overtreatment was omitted [6]. In addition, the same British brochure showed the risk of overdiagnosis after one round of screening, and the cumulative reduction in mortality after five rounds of screening, thus minimizing the harm while exaggerating the benefit.
Failure to inform correctly also addresses the omission of harms such as overdiagnosis and overtreatment.[6]
Editor's note: We will detail in a dedicated paragraph the very same shortcomings in the information given to women in France, which were denounced in this study, and which were also mentioned during the public consultation on screening in 2016 in France. We will come back to this.
c) Opt-out systems
This consists of assigning citizens a pre-booked appointment at the point of the invitation. If the person does not wish to participate, he/she must actively opt out. The non-refusal of the patient is considered de facto as acceptance to participate.
Editor's note: In France, we do not have this system of prebooked appointments, but the system of reminders is widely used if a patient does not show up for a screening mammography appointment (reminders by mail and sometimes SMS).
d) Recommendations of participation
A recommendation to participate in a health procedure does not provide evidence about the effectiveness or appropriateness or benefit of a screening program. Instead, it promotes one option (to participate) as the smartest or best, based on the authority of the source from which the injunction emanates. This is the argument from authority.[7]
Celebrity staging is also widely used in different countries to increase participation. Humorous examples are given in the article by Rahbek et al. In an Icelandic government video, after examining a citizen's rectum, the doctor slaps him on the bottom and exclaims, "More men should follow your example and take care of their own ass" - a recommendation, unaccompanied by factual data.
e) Fear appeals
This is a well-tried lever. By relying on the uncertainty of life and emphasizing the human fear of dying, it is easy to convince.
f) Influence on general practitioners and other healthcare professionals
The most obvious one is the system of reward by remuneration when the professional encourages a patient to participate, called P4P (Pay for performance) or ROSP (Remuneration on public health objectives) in France.
g) Others
It is not used in France but is in force in Uruguay, and it was almost introduced in Germany: it is the legislative influence.
In Germany, in 2007, a law proposal suggested that if an individual did not participate in a cancer screening program and was subsequently diagnosed with the type of cancer for which he or she had been called for screening, then that individual would have to pay double the health tax - a law proposal that was finally rejected.
In total
The authors' analysis shows that there is a common point between the six main categories of influence detailed in the article: they work through psychological biases and personal costs (i.e. time consumption or financial) on non-participation.
The article here focuses essentially on "nudging" populations, a term that refers to anything that predictably changes people's behavior by pushing them into what you want them to do, without any scruples, and even to the point of financial incentives.
Insofar as patient autonomy and informed choice are important, the authors say, the use of such influences is ethically questionable in cancer screening programs where the benefit/harm ratio is complex and scientifically contested.
Therefore, they argue, there is a need to find better ways to facilitate participation by willing citizens, without pushing reluctant citizens to participate. Instead of evaluating cancer screening programs on the basis of participation rates, programs should be evaluated on informed decision rates, regardless of participation or non-participation.
Key points
• This study finds six categories of systematic influences applied to increase participation in national cancer screening programmes.
• The categories of influences work through psychological biases and personal costs of non-participation and might not be compatible with the citizens’ informed choice.
• Research on how to properly implement informed decision models as not to complicate participation for otherwise willing citizens are needed.
Methods of pressure and manipulation by the sanitary structures in France, in particular for breast cancer screening by mammography
We will take up the six methods of influence described and analyse their application in France, specifically concerning breast cancer screening which is our subject of concern. The shortcomings of information in France have been very well identified and described in the report of the citizen and scientific consultation on breast cancer screening (2015/2016) which, let us remember, called for a halt to this screening[8] (observations of multiple failures in the information given to women).
It is important to underline the incredible cynicism of the National Cancer Institute which uses this same publication to improve the participation rate in screening!
Indeed, on the Institute's website, in the section intended for doctors (thematic access "health professionals") this publication is quoted as a basis for improving the participation rate, ignoring the denunciation of the unethical character of the influence techniques by the authors of the study.
"Conducted on the basis of a systematic review of the literature (19 articles) and with the help of experts, this study identifies different types of influence allowing to improve the participation rate in screening programs."
The critical analysis of the Rahbek et al. study is not mentioned at all...
Let's look at the information given to women according to the 6 categories of influence analyzed in the article.
a) Misleading presentation of statistics
Rahbek et al. cite the INCa booklet[9] in Table 5 of the supplements section of their study (TABLE 5. GREY LITERATURE SEARCH RESULTS) as an example of misleading presentation of statistical data, and they denounce the French booklet's presentation of mortality in terms of relative risks. In fact, in the French booklet, the reduction in the risk of dying from breast cancer (this so-called gain in mortality) is announced by INCa to be between 15 and 20%. We have also analysed this booklet and made the same observations about the misleading and embellishing information concerning the supposed gain in mortality from breast cancer screening [10].
When we visit the INCa website[11], which is supposed to guarantee proper information to the population, we immediately come across the same flaw denounced by the publication, here: https://cancersdusein.e-cancer.fr/infos/pourquoi-les-autorites-de-sante-recommandent-de-realiser-un-depistage/ : "International studies estimate that these programs can prevent between 15% and 21% of deaths from breast cancer."
The same presentation can be found again and always on the French Health Insurance website, in spite of the citizens' requests to avoid this pitfall, superbly ignored and scorned by these authorities, which are nevertheless heavily pinned for their failings, as can be seen on the website,
On the French Assurance Maladie website, it is impossible for a patient to obtain information on overdiagnosis or overtreatment. In the search box there are no hits.
But in the tab "organized breast cancer screening" you will find a video made by the INCa and a reference to the page of the Institute.
The benefits, on the official site of the INCa, are largely developed, and the harms are called here modestly the "limits of screening". In the small paragraph 'DIAGNOSIS AND TREATMENT OF SLOW PROGRESSIVE CANCER', overtreatment, a direct consequence of overdiagnosis for women, is never mentioned.
Overdiagnosis is indicated at a percentage of 10 to 20%, figures that are completely obsolete and have been revised upwards for a long time[12].
Even lower numbers appear on the page for professionals: "Based on published studies, overdiagnosis could be in the range of 1-10% or even 20%. "
We had also carried out ourselves a quantitative evaluation of the informative value of this site where the inciting for screening is obvious[14].
The French brochures are again cited in the "supplements" of the Rahbek et al study, item 'MISREPRESENTATION OF HARMS VS BENEFITS'; the authors denounce the omission of overdiagnosis in the official brochures. To be more accurate, overdiagnosis is mentioned in the booklet but very much minimized, and the description of overtreatment, a corollary of overdiagnosis, is completely missing.
Still in the same section, Rahbek et al. denounce the omission by the official French brochures of the risk of exposure to ionizing radiation. We had also noted this point in the analysis of the booklet (reference 11). But in fact this point is mentioned on page 12 of the INCa booklet, which states that: "the risk of death from radiation-induced cancer is of the order of 1 to 10 per 100,000 women who have had a mammogram every 2 years for 10 years."
This is true, but it should be pointed out that this risk increases with the repetition of examinations and incidences. Let us recall that 3 mSv are received on average with a mammography (between 2 and 3 images per breast depending on the needs), which corresponds to already 9 months of annual irradiation (which is 4.5 mSv per year for a French person).
c) Opt-out system
As mentioned above, this system is not used in France. However, if a woman does not go for screening, she will be reminded several times, sometimes even by text message, giving women the impression that screening is mandatory. However, this is not the case, screening is not mandatory and we have provided a pre-filled form on the home page that women who do not wish to undergo mammography screening can send to their departmental screening structure. 15]
At the end of the INCa booklet, it is clearly stated "You cannot or do not wish to be screened. Fill in the questionnaire in the invitation letter and return it to the address indicated. Please be aware that you can change your mind at any time. "
d) Recommendations for participation
The argument of authority is widely conveyed by opinion leaders, a radiologist speaks on the home page of the "breast cancer prevention and screening" website.
In the midst of the Covid pandemic, we saw a renowned oncologist calling on women to continue screening, scaring them and arguing loudly that breast cancer would kill more than the pandemic. When we read that the 100,000 mark was passed in one year (breast cancer causes 12,000 deaths/year), we realize how sordid these counts seem and especially how some media doctors do not hesitate to exaggerate in order to convey inciting and frightening messages.[16]
The stars in France are not to be forgotten, as shown by the TV show " Naked Stars " where celebrities unveil themselves for " the good cause " with messages that are intellectually indigent and insufficient in terms of scientific information.[17]
In 2011, Marie-Claire published multiple photos of French stars who let themselves be photographed naked to "raise awareness" of breast cancer screening, allowing this media a considerable and profitable increase in its sales.[18]
e) Fear appeals.
The organization Pink Ribbon, formerly 'Cancer-du-Sein-Parlons-en' , broadcast a spot in 2015 based on messages related to death (breast cancer, the most common, the most deadly).[19]
The INCa is not lagging behind and in 2018 was published this poster: "This cancer is at the same time the most frequent and the most deadliest in women. Yet if it is detected early, the treatments are generally less burdensome and the chances of recovery greater."
Cancer is constantly associated with a verdict of death, so much so that the medical, societal and media messages are based on a military and bellicose jargon: cancer is an enemy that will inexorably invade the body. The patient either wins or succumbs, despite the "therapeutic arsenal" or the "fight" led by the patient. As soon as a cancer is diagnosed at the mammogram, the feverishness that the doctor shows in making appointments for his patient for other examinations and surgery reinforces the idea of imminent death for the patient. Each newly diagnosed woman feels banished from the world of "normality" and threatened with expulsion from the social system (work, family, insurance, bank, etc.). The stress that some women feel after the announcement is such that they lose all control over their lives, professionally, emotionally and in their families. And this is very well recognized by the other women in the family, friends or professional environment.
f) Influence on general practitioners and other health professionals
In France this is the ROSP system (remuneration on public health objectives)[20].
Note that on the site dedicated to professionals [21], the risk of "unnecessary mutilation of women screened by excess" is well recognized, the controversy and the consultation of 2016 are mentioned, nevertheless the premium is maintained (according to web page of December 29, 2020).
But even worse is the financial incentive offered to the women themselves. Indeed, in 2020 the INCa organized a masquerade of consultation[22] where one item caught our attention, as it proposed to pay women this time in order to bring them to screening.
A citizen has expressed her concern in an article published in the JIM, denouncing the lack of ethical consideration in this proposal for "paid participation"[23].
The manipulation of women is a real scientific topic
Rahbek et al have perfectly identified the shortcomings of the information provided to the public on screening in general, information that remains globally often inciting, which goes against the ethical objectives that we owe to the patient.
The shortcomings and failings of the official French brochures were noted, including those of the INCa, an institute that is supposed to protect the patient.
The booklet of the INCa, already quite imperfect, is sent to women eligible for screening only once at the time of their first convocation when they are 50 years old. In 2017, when the booklet was published, women aged 50 who were first called for screening received it, but women over 50 at that time will never receive it.
And what can be said about the INCa's multi-language brochure, which is even more succinct?
From our point of view, we can only be dismayed and distressed to see to what extent the demands of French citizens, who had, during the 2016 consultation, identified the same problems, have remained unheard and scorned by the French authorities.
ANNEX:
You will find here a table annexed with the original publication, showing the research of the so-called 'grey' literature (brochures and information websites). French brochures are named in several items of misleading communication of data (yellow highlighting).
We have selected for presentation in our article only the examples concerning breast cancer screening, by mammography.
We found that these examples account for about 60% of the total number of examples for all cancers combined: prostate, breast, cervical and colorectal. We can conclude that there is a preferential communication, a hype around breast cancer screening, compared to other cancers.
Master student Department of Public Health, Section of General Practice Research Unit for General Practice, Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen K, Denmark
Christian P. Jauernik
The Research Unit for General Practice, Section of General Practice, Department of Public Health, University of Copenhagen, Copenhagen K, Denmark
Thomas Ploug
Thomas Ploug is Professor of ICT (Information and Communication Technology) Ethics at the Department of Communication and Psychology at Aalborg University in Copenhagen. He holds a Master of Philosophy from the University of Copenhagen and a PhD in ICT ethics from the University of Southern Denmark. His research interests and projects cover topics in different areas of applied ethics, such as ICT ethics, medical ethics and bioethics. He is currently involved in projects on online and offline consent behavior in the health context, and nudging in the health sector. He is head of the research group on communication and information studies, director of the Centre for Applied Ethics and Philosophy of Science, member of the Danish Council of Ethics and the clinical ethics committee of Rigshospitalet, Copenhagen.
John Brodersen, Professor, University of Copenhagen
John Brodersen, the senior author of this article, is a general practitioner with more than ten years of experience in clinical practice. Dr. Brodersen holds a PhD in public health and psychometrics and works as an associate research professor in medical screening at the University of Copenhagen, Department of Public Health, Research Unit and Section of General Practice.
His work was used in the development of the 2020 WHO Screening Guide, which builds on the background papers written by John Brodersen for the 2019 WHO European Technical Consultation on Screening.
He is also a co-author of the 2012 Cochrane booklet on mammographic screening.https://www.cochrane.dk/sites/cochrane.dk/files/public/uploads/images/mammography/mammografi-fr.pdf
He is a member of the Board and Scientific Committee of the non-profit organization "Preventing Overdiagnosis "https://www.preventingoverdiagnosis.net/?page_id=6
His research focuses on the development and validation of questionnaires to measure the psychosocial consequences of false positive screening results. Dr. Brodersen has published numerous articles in peer-reviewed journals.
In the area of self-diagnosis and screening, Dr. Brodersen specializes in the areas of sensitivity, specificity, predictive values, overdiagnosis, informed consent, and psychosocial consequences for healthy individuals when tested.
He also teaches nationally and internationally on evidence-based medicine.
PhD thesis:Brodersen, J 2006 , Measuring the psychosocial consequences of false positive screening results - breast cancer as an example, PhD thesis, Månedsskrift for Praktisk Lægegerning, Department of General Medicine, Institute of Public Health, Faculty of Health Sciences, University of Copenhagen. Copenhagen
REFERENCES
[1] European Network for Prevention and Health Promotion in Family Medicine and General Practice. Available at: http://europrev.woncaeurope.org/
Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.
Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.
According to this publication, there would be a significant reduction in mortality from breast cancer in patients who were monitored.
Here are our comments. We did not mention this study because there is a huge and well-known selection bias, namely that women who do not participate in screening are very different from those who do; and this bias can explain the results as well as the screening itself in this population.
One of the experts who was approached by Medscape Medical News to comment on the new study, Philippe Autier, MPH, MD, PhD, from the University of Strathclyde Institute of Global Public Health at the International Prevention Research Institute, Dardilly, France, questioned the methodology of the study. "This method is incorrect simply because women attending screening are different from women not attending screening," he said. "The former are more health aware and have healthier behaviors than the latter, and this is a well-known fact and supported by the literature."
Dr Autier emphasized that it is practically impossible to control for that bias, which is known as confounding by indication.
"The statistical methods used for attenuating the so-called self-selection are very approximate and based on unverified assumptions," he said. "For this reason, the Handbook on Breast Cancer Screening produced by the International Agency for Research on Cancer clearly stated that 'observational studies based on individual screening history, no matter how well designed and conducted, should not be regarded as providing evidence for an effect of screening,' and the methodology in this paper has never been recommended by the [agency]."
A better way of conducting this type of study would have been to show the incidence trends of advanced-stage breast cancer in Sweden for the entire female population aged 40 years and older, he asserts. Dr Autier used that methodology in his own study in the Netherlands, as previously reported by Medscape Medical News.[4]That study foundt hat in the Netherlands, screening mammography over a period of 24 years among women aged 50 to 74 years had little effect on reducing rates of advanced breast cancer or mortality from the disease.
Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.
Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.
Marie Joelle Jabagi, PharmD, MPH; Norbert Vey, MD, PhD; Anthony Goncalves, MD, PhD; Thien Le Tri, MSc; Mahmoud Zureik, MD, PhD; Rosemary Dray-Spira, MD, PhD
About this study
This is a cohort study. All French women between the ages of 20 and 85 years who were diagnosed with breast cancer and did not die (referred to as "survivors"), between 2006 and 2015, were included and were followed up until the onset of hematological cancer, or until death, or until loss of follow-up, as the case may be. Comparisons were made with all French women in general population enrolled in general health insurance plan each year from 2007 to 2016. Data from the SNDS (containing data from the PMSI and the CepiDC) were analyzed.
Results
The different types of hematological neoplasia considered were acute myeloid leukemia, myelodysplastic syndrome, myeloproliferative neoplasms, multiple myeloma, Hodgkin's lymphoma or non-Hodgkin's lymphoma, acute lymphoblastic leukemia, lymphocytic lymphoma. The incidence (number of new cases) of these different types was estimated and compared to the incidence in women in general population.
In this study of 439,704 French women, women with a diagnosis of breast cancer who had not died from it, had a statistically standardized higher incidence of acute myeloid leukemia and myelodysplastic syndrome compared to women in general population. There was a slight increase in the incidence of multiple myeloma and acute lymphoblastic leukemia.
French women participating in the study who had breast cancer in the last decade were 3X more likely to develop acute myeloid leukemia and five times more likely to develop myelodysplastic syndrome than women in general population. Several previous studies have linked these pathologies to chemotherapeutic agents, radiotherapy, and taxotere therapy (adjuvant treatment of breast cancer, see HAS 2015 advisory). (See studies [1])
It cannot be ignored that hematological risk of malignant neoplasm reaches peaks within specific time frames after breast cancer.
The annual incidence of acute myeloid leukemia in these patients from this study, increased during the first few years following diagnosis of breast cancer, with an early peak around year three and a subsequent peak around year eight. This finding is consistent with previous studies indicating the presence of 2 types of acute lymphocytic leukemia associated with treatment.
The authors suggest that the latency of onset may depend on the age of the patient at diagnosis, type of therapy and dosage regimen, and also on the limited time of follow-up in the study (even later cases may occur that have not been reported here).
The majority of secondary leukemias are of the myeloid type, but it is estimated that acute secondary lymphoblastic leukemias account for 10% to 12% of all secondary leukemias, with breast cancer being the most common cancer causing these secondary pathologies. In this study, there was a two-fold increase in the incidence of acute lymphocytic leukemia in breast cancer "survivors". Some studies showed that irradiation and chemotherapy were associated with pathogenesis [2], while other studies suggested that prior therapy plays a less important role in secondary acute lymphocytic leukemia than genetic predisposition [3].
A 50% increase in the incidence of multiple myeloma was observed in breast cancer survivors in this study. This slight increase has not been reported and needs to be further investigated, particularly the role of susceptibility due to heredity in BCRA1 and BCRA2 mutation carriers. [4]
Conclusion
This study reveals that acute myeloid leukemia, myelodysplastic syndrome and acute lymphoblastic leukemia are more common in treated women who do not die from breast cancer than in women in the general population; this is of concern and according to the authors, ongoing surveillance of hematological malignancies and further research into the underlying mechanisms of these diseases is needed.
This study is intended to better inform practicing oncologists; patients with a history of breast cancer should be informed of the increased risk of developing certain hematologic malignancies after their first cancer diagnosis.
Recent discovery of genetic signatures that guide treatment decisions in early stages of breast cancer could reduce the number of patients exposed to cytotoxic chemotherapy and its complications, including hematological cancers[5].
It is therefore necessary to continue monitoring trends in the occurrence of hematological cancers, especially as approaches to cancer treatment are evolving rapidly. Further research is also needed to evaluate treatment modality in cases of genetic predisposition to secondary malignancies.
Comments :
(EDITOR'S NOTE)
Concerns about overdiagnosis are all the more justified because women, some of whom are at high risk and unaware of it [6], may be receiving radiation therapy that they would not have needed, and are being precipitated by screening for a disease they would not have had in its absence, with potential risks inherent in treatment, including secondary hematological diseases.
This has been shown in studies that suggest that risks of treatment may outweigh the expected benefit of screening. [7]
As our dotted poster on the home page of the site (bottom of the page, "poster") shows, the benefit/risk balance in screened women is far from being in favor of benefit, due to overdiagnosis, radiation-induced cancers, radiation-induced coronaritis, surgical and anesthetic accidents, post-treatment thromboembolism, and secondary hematopathies.
The Cancer Rose Collective regrets that these elements are not explicitly detailed in the information brochure given to women who are part of the new study on personalized screening, the MyPebs study. Overdiagnosis is minimized at rates that are currently obsolete, overtreatment, a tangible consequence resulting from overdiagnosis for women, is not stated, and consequences of treatment are not mentioned[8].
References
[1] Studies about relation between breast cancer treatment and Hematologic Malignant Neoplasms:
SmithRE,BryantJ,DeCillisA,AndersonS;National Surgical Adjuvant Breast and Bowel Project Experience. Acute myeloid leukemia and myelodysplastic syndrome after doxorubicin-cyclophosphamide adjuvant therapy for operable breast cancer: the National Surgical Adjuvant Breast and Bowel Project Experience. J Clin Oncol. 2003;21 (7):1195-1204. doi:1200/JCO.2003.03.114
PragaC,BerghJ,BlissJ,etal.Risk of acute myeloid leukemia and myelodysplastic syndrome in trials of adjuvant epirubicin for early breast cancer: correlation with doses of epirubicin and cyclophosphamide. J Clin Oncol. 2005;23(18):4179-4191. doi:1200/JCO.2005.05.029
BeadleG,BaadeP,FritschiL.Acute myeloid leukemia after breast cancer:a population-based comparison with hematological malignancies and other cancers. Ann Oncol. 2009;20(1):103-109. doi:1093/annonc/mdn530
Le Deley M-C, Suzan F, Cutuli B, et al. Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony- stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer. J Clin Oncol. 2007; 25(3):292-300. doi:1200/JCO.2006.05.9048
Galper S, Gelman R, Recht A, et al. Second non breast malignancies after conservative surgery and radiation therapy for early-stage breast cancer. Int J Radiat Oncol Biol Phys. 2002;52(2):406-414. doi:1016/S0360-3016 (01)02661-X
RenellaR,VerkooijenHM,FiorettaG,etal.Increased risk of acute myeloid leukaemia after treatment for breast cancer. Breast. 2006;15(5):614-619. doi:1016/j.breast.2005.11.007
CurtisRE,BoiceJDJr,StovallM,FlanneryJT,MoloneyWC.Leukemia risk following radiotherapy for breast cancer. J Clin Oncol. 1989;7(1):21-29. doi:1200/JCO.1989.7.1.21
HsuW-L,PrestonDL,SodaM,etal.The incidence of leukemia,lymphoma and multiple myeloma among atomic bomb survivors: 1950-2001. Radiat Res. 2013;179(3):361-382. doi:1667/RR2892.1
AndersenMK,ChristiansenDH,JensenBA,ErnstP,HaugeG,Pedersen-BjergaardJ.Therapy-related acute lymphoblastic leukaemia with MLL rearrangements following DNA topoisomerase II inhibitors, an increasing problem: report on two new cases and review of the literature since 1992. Br J Haematol. 2001;114(3):539-543. doi:1046/j.1365-2141.2001.03000.x
CardosoF,van’tVeerLJ,BogaertsJ,etal;MINDACTInvestigators.70-Gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717-729. doi:1056/NEJMoa1602253
SparanoJA,GrayRJ,MakowerDF,etal.Adjuvant chemotherapy guided by a21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111-121. doi:1056/NEJMoa1804710
Cancer Rose est un collectif de professionnels de la santé, rassemblés en association. Cancer Rose fonctionne sans publicité, sans conflit d’intérêt, sans subvention. Merci de soutenir notre action sur HelloAsso.
Cancer Rose is a French non-profit organization of health care professionals. Cancer Rose performs its activity without advertising, conflict of interest, subsidies. Thank you to support our activity on HelloAsso.
