Cancer Rose · Cancer Rose

30 November 202030 December 2020

Absence of benefit from mammograms in women aged 40-50 years confirmed by final results of UK Age Trial

Cancer Rose, 16 August 2020

In August 2020, the final results of the UK Age Trial [I] were published.

For women aged 40-49 years

Between 1990 and 1997, this British trial included approximately 161,000 women aged 39 to 41.Women were randomly selected and an annual mammography up to the age of 48 was proposed for about one in three (53,883 women), while the remainder had no screening. All the women then joined the standard British screening program, which includes a mammogram between the ages of 50 and 69 every three years. The main aim of the trial was to determine whether screening could reduce mortality from breast cancer before the first mammogram of standard screening program, which starts after the age of 50.

Prior to these results, no evidence of a benefit

After 10 years, the UK Age Trial results showed a statistically significant decrease in the number of breast cancer deaths before routine screening program. The authors announced a 25% decrease in relative value, but this actually corresponds to a gain of only 4 deaths from breast cancer per 10,000 women screened and followed for 10 years. Furthermore, the results did not demonstrate a decrease in total mortality (or all-cause mortality).*
There was no statistically significant decrease in deaths from cancer when the results of all nine studies that included women aged 40-49 (not just the UK Age Trial) were considered.

*Only the total mortality includes all elements of patient management, hence also the effects of treatment, overdiagnosis and overtreatment.
This makes more sense because any cancer detected will be treated, the treatments themselves sometimes causing deaths, which will be counted in the «all cause mortality» , thereby better reflecting the screening reality.

After these results, even less evidence of a benefit

After 23 years, the UK Age Trial results no longer indicate a significant decrease in the number of breast cancer deaths in women screened between the ages of 40 and 49.
The authors of the trial write: «Overall, there was no significant reduction in breast cancer mortality in the intervention group compared with the control group» (p4 penultimate paragraph (ref1 PDF)).

Prior to these final results, analyses that considered the results of all trials already concluded that there was no measurable benefit. Or, at the time, the UK Age was one of those trials that supported screening program.
With these results, we can be even more affirmative in saying that attempting to screen for breast cancer before the age of 50 does not have any tangible benefit.

When should we expect a re-assessment of these results?

Another trial is underway to evaluate the possible benefit of expanding screening to women before age 50 and after age 69: the Age X Trial. Its results are not expected before 2026.

Controversy in Great Britain

The publication of these results caused a great deal of controversy in Great Britain. Not because they were challenged or questioned, because the trial is of a good methodological level.
But because the authors [iii], no doubt disappointed with the results, tried to hide their negative character by insisting on the results obtained at the end of a 10-year follow-up and not at the end of the 23-year follow-up.
Some popular media journalists were thus prompted to write that the results were in favor of the effectiveness of the screening, hence the controversy [iv].

REFERENCES

[i] Duffy SW et coll. "Effects of mammogrpahic screening from age 40 years on breast cancer mortality (UK Age trial) : final results of a randomised, controlled trial" The Lancet Oncology online. 12 août 2020. Website www.thelancet.com/oncology. Doi : 10.1016/S1470-2045(20)30398-3
Document PDF of the study

[ii] Nelson HD et coll. "Screening for Breast Cancer: A Systematic Review to Update the 2009 U.S. Preventive Services Task Force" Recommendation. Evidence Synthesis No. 124. AHRQ Publication No. 14-05201-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2016.
See particularly table 28 page 128.

[iii] Who are the authors of this study?
They are Duffy’s team and his staff from Queen Mary University in London.
Dr.Duffy is already well known in the world of screening, as he is one of the oldest pioneers in the promotion of screening and has published several studies seeking to quantify overdiagnosis, most often at its lowest range, according to him from 1 to 10%. (Overdiagnosis in mammographic screening for breast cancer in Europe: a literature review. Puliti D, Duffy SW, Miccinesi G, by Koning H, Lynge E, Zappa M and the EUROSCREEN Working Group. J Med Screen 2012;19 Suppl1:42-56.)

This was a review of studies, and this work had been highly controversial as a source of multiple rather crude biases. In their analysis the authors, Duffy and Puliti, had deliberately excluded many reference studies, Zahl’s in 2008 and Junod’s in 2011( Junod B, Zahl P-H, Kaplan Rm, Olsen J, Greenland S. An investigation of the apparent breast cancer epidemic in France: screening and incidence trends in birth cohorts. BmC Cancer. 2011 Sep 21;11(1):401.)

The Prescrire Review in 2006, after a careful analysis, as well as the exhaustive analysis made by Professor Autier, and many others even more recent, currently conclude that the rate of overdiagnosis may be between 30 and 50%.
Revue Prescrire :
*Dépistage des cancers du sein par mammographie Deuxième partie Comparaisons non randomisées : résultats voisins de ceux des essais randomisés. Rev Prescrire. 2014 Nov;34(373):842–6.
*Dépistage des cancers du sein par mammographie Première partie Essais randomisés : diminution de la mortalité par cancer du sein d’ampleur incertaine, au mieux modeste. Rev Prescrire. 2014 Nov;34(373):837–41.
*Dépistage des cancers du sein par mammographies Troisième partie Diagnostics par excès : e et indésirable insidieux du dépistage. Rev Prescrire. 35(376):111–8.

[iv]
How screening promoters try to justify the alleged success:
In the screening group, after 10 years, for every 10,000 women in the screening group, there were 14 deaths from breast cancer, while for every 10,000 women in the control group, there were 20 deaths.This relatively small benefit (including adverse effects of screening) was statistically significant. It is this difference that the authors rely on to argue that there could be a benefit, which they proclaim as “25%” (20-14 / 20 = 25%).

However, at the end of the follow-up, after 23 years, for 10,000 women in the screening group, there were 39 deaths from breast cancer, while for 10,000 women in the control group, there were 44. This time the difference is not statistically significant. And in relative terms it is 44 – 39 / 44 = 11%.
Above all, the important thing to remember: no significant difference in all-cause mortality was found between the two groups, neither after 10 years, nor at the end of the follow-up, after 23 years
At the end of the trial, there were 650 deaths per 10,000 women in the screening group and 648 deaths per 10,000 women in the control group.

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30 November 202030 December 2020

International reactions to attempts to cover up screening failure in a publication

24 August 2020 by Cancer Rose

We have previously reported on a publication by Stephen Duffy and al. about the final results of the UK Age Trial on breast cancer screening by mammography [1].
This is the "nth" publication by this author, which attempts to show the benefits of screening mammography for women, even at an early age, in this case from the age of 40.
We explained that, contrary to the result that Prof. Duffy is victoriously brandishing, the most important statement of his study was :
"After more than 10 years of follow-up, no significant difference in breast cancer mortality was observed in the intervention group compared with the control group, with 126 deaths versus 255 deaths occurring in this period (0-98 [0-79-1-22]; p=0-86). Overall, there was no significant reduction in breast cancer mortality in the intervention group compared with the control group, with 209 deaths in the intervention group versus 474 deaths in the control group by the end of follow-up (0-88 [0-74-1-03]; p=0-13). »

Therefore, no benefit can be expected from screening.

But what does the international scientific community think of this study?

1) Position paper by Professor Anthony MILLER [2], professor at the University of Toronto [3].

Professor Miller is a leading expert in breast cancer screening since many years, as evidenced by his publications. [4] [5]
For this scientist, the absence of a control group without screening in the study is critical for drawing any conclusions about the interest and possible benefit of screening.
This point is essential, because the omission of a control group without any screening is a major shortcoming that we highlighted in another ongoing trial on screening, namely the MyPeBS study [6], a European trial that aims to compare a personalized screening strategy to the standard screening in 4 European countries and Israel.

Again, the use of a control group "without any screening" was carefully omitted, which was the only way to know whether or not screening would be beneficial compared to women who had never been screened.

While no conclusions can be drawn from a medical intervention without a control group which is not affected by the process being tested, Duffy and al. nevertheless assert :
"There was a substantial and significant reduction in breast cancer mortality, of the order of 25%, associated with the invitation to yearly mammography between age 40 and 49 years in the first 10 years."
It should also be noted that the 25% reduction (Relative Reduction) put forward by the authors is far from being "substantial", since the absolute reduction is actually only 0.04% [7].
Anthony Miller also contests, with references [8], the minimization of over-diagnosis, which Professor Duffy persistently tries to minimize in his demonstration: "Results with respect to breast cancer incidence suggest at worst modest overdiagnosis in this age group, and that any overdiagnosed cancers would otherwise be diagnosed at NHSBSP screening from age 50 years onwards. Therefore, screening in the age group of 40-49 years does not appear to add to overdiagnosed cases from screening at age 50 years and older. There might have been some overdiagnosis in the intervention group and during the intervention period, which was balanced when the control group received screening in the NHSBSP. However, we cannot directly observe or estimate overdiagnosis in a trial in which the control group also receives screening, albeit later than the intervention group. »

Studies on over-diagnosis are numerous and attest to this phenomenon in all age groups [10].
However, authors Duffy et al. concede: “we cannot directly observe or estimate overdiagnosis in a trial in which the control group also receives screening, albeit later than the intervention group”.

We therefore again come back to the fundamental obstacle: without a group free of any screening, no reliable conclusion can be drawn either on the benefits in terms of mortality or on the evaluation of over-diagnosis.

2) Other scientists

Journalist Jacqui Wise [11] published an analysis of this study in the British Medical Journal, including remarks made by other scientists about the study.

A-Reaction by K-J.Jorgensen [12]

Karsten Juhl Jørgensen, acting director of the Nordic Cochrane Centre in Copenhagen, told the BMJ : “Since the trial was initiated, breast cancer mortality in the UK in the included age range has been cut by half due to major improvements in treatment, including centralisation and specialisation of care, as well as better systemic treatment.
“…we can be reasonably sure that any benefit in absolute terms will be less today, as there are simply substantially fewer lives to be saved ».

The trial was originally planned to include 195,000 participants, but the number was revised due to slow recruitment. Jørgensen said, Jørgensen said, “As the 160 000 women enrolled in this study was not enough to show any difference in overall mortality, the study really cannot be used to conclude that ‘lives were saved.’
“The study tells us very clearly that any benefit of breast screening in this young age group is very small in absolute terms, as you would expect due to the inherently low risk of breast cancer death before age 40 years.”
In other words, it is impossible, in a population with a very low incidence of breast cancer (young women) [13], to conclude that a reduction in deaths can be obtained through screening. This is another factor that the author of the study has not taken into account.
Jorgensen also pointed out the number of false alarms experienced by women in the test group, i.e. 18% of the women during the trial period.

B-Reaction of V. Prasad [14]

For Vinay Prasad, Associate Professor at the University of California, San Francisco : “It is disappointing to see the authors of this study continue to promote misleading rhetoric ».
”Saves lives” said V. Prasad “means that women, as a result of doing this, live longer than those who do not do it. That did not occur in this dataset. Quite the opposite.” He added “The authors note a very small reduction in death from breast cancer which is tiny, and so small it does not impact dying for any reason.” [15].

D-Reaction from scientists of Sydney University in the Lancet.

https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30528-3/fulltext

"An earlier report on the trial (Moss SM Effect of mammographic screening from age 40 years on breast cancer mortality at 10 years' follow-up: a randomised controlled trial.Lancet. 2006; 368: 2053-2060), where mean follow-up was 10·7 years, did not find a significant difference in breast cancer mortality between groups, and there was no breast cancer mortality benefit in the trial overall (after a median follow up 22·8 years). "

E- Two additional responses, from eminent scientists, were made to Wise's article in the BMJ [16]

First of all, the opinion of Professor Michael Baum, Professor Emeritus of Surgery and Invited Professor of Medical Humanities at University College London.
For Professor Baum there are only two significant outcome measures in the practice of medicine for the patients we follow: length and quality of life. All other outcome measures should be considered, in his view, as surrogates.
M Baum comments :
« This trial claims that screening woman under the age of 50 for breast cancer, will save lives without having a detrimental impact on Qof (Editor note : quality of life). Starting with the first claim let us look at the raw numbers without any modelling or “mathemagic”, and here I acknowledge the help of Dr Vinay Prasad. The percent of deaths from breast cancer in the intervention and control arms were, 0.39 v 0.44, whilst deaths from all causes were, 6.5 v 6.5. Little evidence for screening as a “life saver”.

“As there was no formal assessment of QoL then we have to make the assumption that over-diagnosis or false positive results might impact on the woman’s psychological wellbeing to which can be added the toxicity of any surgery, radiotherapy or systemic therapy as the consequence of over-diagnosis”.

M. Baum estimates, based on available data, that 35% of women experience false alarms and over-diagnosis during the intervention period, with the consequent impact on their quality of life. According to Michael Baum, the authors' conclusions are unfortunately mainly driven by an ideological attitude that is not worthy of scientists.

Next, the opinion of Hazel Thornton, Honorary Visiting Research Fellow in the Department of Health Sciences at the University of Leicester who also comments.
« Recruitment of the 160,921 women in this study took place from 1990 to 1997. We learn that women in the intervention group were unaware of the study. In other words, they were denied their right to consider whether they wished to participate in the study. Screening by mammography is not without potential for harm: properly informed consent should have been sought from these asymptomatic citizens. The fundamental principle of the Declaration of Helsinki, of respect for the individual and the right to make informed decisions, was ignored.[17]

For H. Thornton, the problem with organized screening is that it focuses on the women who benefit from it, while neglecting the hundreds of women who go through this public health process and suffer harm, in some cases even psychological harm.

H. Thornton also refers to the current pandemic and its economic stakes.
« They (Editor note, those who talk about saving lifes) seem unable to see the wasteful disproportionateness of their stance at a time when currently, in the UK, for example, 1.85 million people are waiting for treatments put on hold in this time of pandemic. Only Covid-19 seems to have had the power to put a stop to breast screening when evidence, reason and clamours for distributive justice have not. »

In conclusion

We therefore see that many international scientific personalities are questioning Professor Duffy's conclusions.
This study and the sound analyses show once again, and this against the conclusions of the author, that breast cancer screening by mammography does not bring any benefit.
We remind that all published studies, and even the Duffy ‘s study presented here as "positive", demonstrate year after year, the ineffectiveness of screening in reducing mortality from breast cancer.
More and more voices are being raised calling for an end to this ineffective screening that has adverse effects on women.
It is quite disturbing to note that the scientific controversy, now almost swept away by ever-increasing evidence of the ineffectiveness of the program, is once again being renewed by the beliefs and ideology of scientists, as raised by Mr. Baum, and that these beliefs and ideology are leading these scientists to engage in manipulations of figures in order to erase the bitter failure of the results of an old trial, which was very well conducted, and whose conclusions on the failure of screening are nevertheless implacable.
Moreover, as Jorgensen and Thornton point out, all of these screenings have a cost that would certainly be better used elsewhere, especially in this epidemic period. Not to mention the cost of false alarms, both financial and psychological, that women have to face.

In addition, as Thornton points out, there is a lack of informed consent, as well as manipulative information which are often used with women.
In the next two articles, we will refer to this crucial issue of informing women about screening, and we will relate how screening promoters deliberately manipulate the information they give to women, when they give it….

References

[1] https://cancer-rose.fr/en/2020/11/30/absence-of-benefit-from-mammograms-in-women-aged-40-50-years-confirmed-by-final-results-of-uk-age-trial/
[2] https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30428-9/fulltext?rss=yes
[3] https://www.dlsph.utoronto.ca/faculty-profile/miller-anthony-b/
[4] https://pubmed.ncbi.nlm.nih.gov/24519768/
[5] https://cancer-rose.fr/en/2020/12/30/impact-of-screening-mammography-on-breast-cancer-mortality/
[6] Read : https://cancer-rose.fr/en/2020/11/30/letter-of-4-collectives-on-the-subject-of-mypebs-study/
[7] https://cancer-rose.fr/en/2020/11/30/absence-of-benefit-from-mammograms-in-women-aged-40-50-years-confirmed-by-final-results-of-uk-age-trial/
[8] references quoted by A. Miller :
Forrest APM Aitken RJ,Mammography screening for breast cancer. Annu Rev Med. 1990; 41: 117-132
Marmot MG Altman DG Cameron DA Dewar JA Thompson SG Wilcox M-The benefits and harms of breast cancer screening: an independent review. Br J Cancer. 2013; 108: 2205-2240
Miller AB To T Baines CJ Wall C-The Canadian National Breast Screening Study-1: breast cancer mortality after 11 to 16 years of follow-up. A randomized screening trial of mammography in women age 40 to 49 years. Ann Intern Med. 2002; 137: 305-312
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
Baines CJ To T Miller AB-Revised estimates of overdiagnosis from the Canadian National Breast Screening Study. Prev Med. 2016; 90: 66-71
[9] National Health Service Breast Cancer Screening,
[10] See part "overdiagnosis" in this article: https://cancer-rose.fr/en/2020/12/17/mammography-screening-a-major-issue-in-medicine/
[11] https://www.bmj.com/content/370/bmj.m3191
[12] https://www.bmj.com/content/370/bmj.m3191
[13] Hill C. Screening of breast cancer. Presse med. 2014 mai;43(5):501–9

30 November 202030 December 2020

An unexpected side effect of the covid epidemic-19

The following is the view of two researchers regarding the long-term contribution of suspending cancer screening, to the advancement of cancer knowledge.

Gilbert Welch (Centre for Surgery and Public Health at Brigham and Women's Hospital and author of "Less Medicine, More Health")
And Vinay Prasad (oncologist, Associate Professor of Medicine in Oregon Health and Science University et auteur de "Malignant: How Bad Policy and Bad Medicine Harm People With Cancer")
https://edition.cnn.com/2020/05/27/opinions/unexpected-side-effect-less-medical-care-covid-19-welch-prasad/index.html

Synthesis by Cécile Bour, MD, 28/05/2020

We had already recently reported the views of Judith Garber, a political and health policy scientist at the Lown Institute, and also whose of Susan Bewley, Professor Emeritus of Obstetrics and Women's Health at King's College London and President of HealthWatch.

According to the authors, due to the fact that medical care services were overwhelmed by the epidemic, some patients certainly suffered harm on their health.
For others, though, the two authors suggest that the delay may have been beneficial.
In addition to the effect of the decrease in surgical interventions, emergency room admissions, requests for additional biological and radiological examinations, and the increase in telemedicine, the two researchers review the impact of suspending cancer screening.
Previous research on the global effects of physician strikes has suggested a decrease in mortality concomitant with reduced medical consumption. It therefore seems relevant to carefully study mortality trends in 2020 and to disentangle Covid-related deaths from other causes of death. It would be just as important to look at inequalities according to socio-economic background: the interruption of medical care may reduce mortality among the over-medicated wealthy, but the opposite phenomenon is feared among the poorest.

The screening area

Suspending cancer screening is one of the areas to be studied according to Welsch and Prasad. For them, there is no doubt that the decline in mammography will lead to a decrease in the number of breast cancers diagnosed. But is this a bad or a good thing?
This is a good opportunity to study what will happen in American cancer statistics when screening resumes, in the opinion of these authors.
They expect one of two observations:

Breast cancer rates might "catch up" with the delay in diagnosis, meaning the deficit in cancer diagnoses during the pandemic would be matched for by a surplus of cancers in subsequent years. In other words, any cancers not detected in patients during the pandemic would eventually be found afterwards.
The alternative would be that breast cancer diagnoses would never catch up…
Why ?
Years ago, researchers observed this phenomenon in Norway. Welsch and Prasad refer here to the famous Oslo Institute study of 2008: in a group, women aged 50-64 years had three mammograms in six years, and at the end of six years it turned out that they had more invasive breast cancers detected than women in the comparison group, who had only one mammogram after six years. If all breast cancers were expected to become symptomatic, there would have been as many in both groups. There is no reason why there should be fewer in the group that was not regularly screened, except that breast tumors that never expressed themselves and even regressed spontaneously were detected in excess in the group that had more frequently mammography. This study was at the origin of the demonstration and quantification of overdiagnosis. (See our brochure).

A mammographic procedure done later and less frequently therefore leads to fewer breast cancer diagnoses. It could be argued that this deficit eventually manifests itself in undetected tumors appearing within a longer time frame, around 5, 10 or 25 years. However, this is not the case; this deficit is never caught up even after 25 years of follow-up, as Miller's study shows.
The results of the 2008 Oslo study suggest that some small cancers regress on their own. Question: could this be happening now during the Covid-19 pandemic? And could it be highlighted?

In the article the authors also look at the decline in heart attacks and strokes observed during this period. These diseases were either under-diagnosed or there were actually fewer of them?
Who benefited from this period of less medicalization, and who lost?

Conclusion of the authors

We won't find the benefits unless we look for them, say Prasad and Welsch. We need physician-researchers who are willing to ask hard questions about the services they provide - questions that may threaten their own professional/financial interests.

Covid-19 provides a once in a lifetime opportunity to study what happens when the well-oiled machine of medical care downshifts from high to low volume in order to focus on acutely ill patients. It will be comfortable for physician researchers to study what was lost. It will be courageous for them to study what was gained.

Our opinion

Here, the two researchers present and highlight the question of overdiagnosis and discuss its causes (spontaneous regression of a slow-growing/null tumor), rather than trying to quantify it.
Indeed, the period of suspending screening is likely to be too short for examining its impact reliably. For that it would require that the interruption last two or three years or more (as in the Oslo study comparison group, where the time period for mammography non-examination in the comparison group was 6 years), and that this interruption concerns people who would have been eligible within that time period, according to the initial schedule, as well as that there be no attempt to catch up with the delay.
In our situation, only a few months of over-diagnosed cancers will disappear.
Already in our country the INCa has been rushing, although the epidemic is not yet totally behind us, to send a note to the ARSs (Regional Health Agency) asking to set up a timetable to catch up with the screenings not carried out! (Page 2)
"A plan to catch up on screening not carried out will be established by each CRCDC (regional coordination centers for cancer screening), depending on the estimated number of screenings not carried out and on the epidemiological situation in the territories, its own resources and the methods for resuming activity".
It should be noted that there is an obsessively technocratic concern about the activity indicators of the screening centers, there is no question of reflecting on the possibility of a study based on the data collected during the suspension of screening period, no, it is a question of catching up on indicators that would have lagged behind schedule for the last three months.
A Danish physician colleague confirms that in Denmark, as well, the reactivation has also taken place, and it is not lagging behind….

Another reflection is that if we will find only a slight reduction in incidence due to the short duration of suspending cancer screening, it will be very difficult to detect reliably the eventual compensatory increase mentioned by the authors, or on the contrary the absence of a compensatory increase, not to mention the fact that tumors that disappear by themselves (the over-diagnosed) need nevertheless at least several months, if not years, to disappear.

30 November 20195 November 2021

What is metastasis ?

A metastasis is a secondary tumor site, originating from primary tumor cells that have become detached from it and then transported to nodes or secondary organs via the lymphatic and/or blood circulation. Breast cancer, whether it has pejorative biological characteristics, is likely to produce metastases.
The organs that may be secondarily affected are the bones, brain, liver, lung…..

The risk of developing metastases in the case of breast cancer depends on the molecular characteristics of the original tumor. According to several studies, aggressive, fast-growing breast cancer, which rapidly becomes large and metastatic from the outset, does not develop from every small lesion, but from a subpopulation of small lesions with biological factors that are pejorative from the outset.

Since being detected, the rates of metastatic cancer have not decreased over the past 20/30 years, although this is one of the objectives of screening, together with the decline in mortality.

Read: https://cancer-rose.fr/en/2020/12/17/mammography-screening-a-major-issue-in-medicine/

29 November 20195 November 2021

What is My PEBS ?

Mypebs (my personal breast screening) is a European study that should last 6 years and recruit 80,000 women, aged between 40 and 70, in 5 countries (Italy, France, Israel, Belgium and the United Kingdom).
The defined objective of the study is to verify whether individualized screening, i.e. based on each woman's lifetime risk of developing breast cancer, would be more effective in reducing the number of advanced cancers (stage 2 and above) than current standard mass screening.

BUT IN REALITY, THE STUDY WILL SIMPLY BE LIMITED TO DETERMINING WHETHER INDIVIDUALIZED SCREENING WOULD NOT MISS TOO MANY SERIOUS CANCERS COMPARED TO STANDARD SCREENING.

This is called a "non-inferiority test". If the new screening, or individualized screening, miss less than 25% serious cancers more than in the standard screening, it will be arbitrarily considered as being " non-inferior ", and after all, the two methods would be considered equivalent.
In other words, the question is whether the new strategy is not less effective than the original one, assuming that if there are, for example, 24% (less than 25%) more serious cancers, the results are declared "non-inferior". The authors will argue that both types of screening are equally effective, and the study will be declared a success.

There are several methodological flaws on Mypebs study :

Incomplete and misleading brochure given to participants, minimizing the problem of over-diagnosis and omitting the problem of over-treatment.
There is no comparison group of "unscreened" women, which means that the over-diagnosis in the screened groups cannot be quantified compared to a group of unscreened women.
The software used to "calculate" the individual risk of each woman according to her age, her personal and family history, her breast density, has no scientific validity and will be "tested" during the study with possible readjustments.
Additional mammograms will be carried out for certain women included in the study from the age of 40 onwards, whereas the irradiation of the breast exposes them to a real risk of DNA chains breakage of the breast cells in this young age group.

To better understand the specificities and flaws of Mypebs, Cancer Rose has created a portal dedicated to studying and decoding the My PEBS study.
You can also find an analysis here, made by our statistician, Dr Vincent Robert: http://www.mypebs-en-questions.fr/index.php

20 November 20176 December 2021

What is “high risk”?

FIRST

What is a "family at risk"?

Having a previous family history case, particularly a direct one, is not proof of being a "at-risk" person, despite what is commonly thrown at women as a scarecrow.

We receive frequent testimonials from young women who have been unnecessarily alarmed and, more importantly, compelled to undergo unnecessary and potentially dangerous over-medication.

What about genetic mutation testing for women? When should it be done?

The independent publication Prescrire, Volume 36 N°388/February 2016, presents this topic.

BCRA1 and BCRA2 gene mutations are autosomal dominant, and women with these mutations have a more considerable and earlier risk of breast or ovarian cancer than the general population.

-For the BRCA1 mutation, the median age of onset is 40 years, and the cumulative risk of developing cancer at age 70 is 51 percent to 75 percent.
-For the BRCA2 mutation, the estimated cumulative risk ranges from 33% to 55%.

According to the journal Prescrire, the following criteria should be considered when proposing an oncogenetic consultation:

-Three people in the same branch with breast cancer before age 70,

-Two people in the same branch with cancer before age 50

-One person with ovarian cancer

-One person with breast cancer diagnosed before age 40, or a bilateral form, the first before age 50, or a hormone receptor-negative cancer that occurred before age 60.

The oncogenetic consultation will be requested in these circumstances, based on the score table below.

Eisinger score

The Eisinger score is a decision aid for requesting an oncogenetic consultation.

We present it below (downloadable):

In families where there are multiple cases of breast cancer, the following conditions may arise:

A- Mutation found in a woman of the family presenting breast cancer.

This genetic mutation search provides valuable information to women in the family

Women who are carriers have a higher risk, while women in the same family who are not carriers have the same risk as to the general population.
Suppose a woman in the family decides to search for a mutation in the BRCA1 or BRCA2 genes because of her genealogy and finds herself to be a carrier of a deleterious mutation in these genes. In that case, her risk of developing breast cancer appears to be high, which is also high for her relatives.

B- No mutation found in women with breast cancer.

Either there is no mutation, and the patient has a form of cancer without a genetic cause, or there is a mutation, but it may be an unidentified genetic cause.
As a result, the women in her family will be uncertain whether or not this cancer is inherited. This cancer's risk of inheritance isn't as high as it is when a BRCA mutation is found, but it is higher than in the general population.

Because of the uncertainty, it's necessary to look into the genealogy, which has its own set of uncertainties and imprecision.

C- The breast cancer patient has not undergone genetic testing.

This provides useless information to women's relatives. The sick person may have had an unknown mutation, she may be mutation-free, but the mutation could be present in family members.

REMEMBER THE FOLLOWING:

- Either the person has a family member with a mutation but is mutation-free, her risk will be similar to the general population.

- Either she is a carrier of the mutation, and her risk of developing breast cancer can be estimated, which will be higher than in the general population.

- However, for certain women, there may still be a lot of uncertainty about their family's breast cancer risk:

*In women who have had breast cancer in the family but have not had a mutation in one of the cases,
*In women with a personal negative genetic mutation search, with a genealogy presenting several breast cancer cases, but without any search performed on the sick members.

Summary of guidelines according to the situation, based on the Prescrire publication.

Published in "La Revue Prescrire" May 2016/Tome 36 N°391-p.355 to p.361

The authors provided different options based on the risk circumstance (carrying a mutation, no mutation but one case in the family, no mutation but a family 'history'); we tried to synthesize these situations in a table (below, downloadable).

First of all, who are the subjects at risk?

-a woman with a case of breast cancer in a first-degree relative (mother, sister, daughter) before age 40.

-two women with breast cancer in the first or second-degree family.

-affected male relative, first or second degree

-woman of the family in the first or second degree affected by ovarian cancer.

When no genetic mutations are found in these families, the family risk remains quite uncertain.

For further explanation, see the article: https://cancer-rose.fr/en/2021/01/29/high-risk-of-breast-cancer-and-mammography-in-practice/

Who should be advised to have a prophylactic mastectomy (breast removal for the prevention of cancer)?

Synthesis of an article entitled "to whom to propose a prophylactic mastectomy" published in the journal 'Réalités en Gynécologie-Obstétrique- N°185_janvier 2017'; Authors: A.Kane, CH. Dehghani, E.Vincens from the Department of visceral and gynecological surgery, Groupe hospitalier Diaconesses Croix Saint-Simon, Paris

The conclusions are:

- For patients who are carriers of the genetic mutation (BRCA1 and BRCA2 mutation but especially BRCA1), unaffected, especially for young patients and those with a heavy family history, preventive mastectomy corresponds to the best means of prevention and must be discussed with them.

- For patients who carry a mutation or have a heavy family history and who have had breast cancer, preventive bilateral or contralateral mastectomy in the event of removal of the breast during first cancer seems to be of interest in terms of survival and reduction in the occurrence of second breast cancer. The HAS recommends it.

The benefit is very uncertain and highly overestimated for patients who have had breast cancer but without genetic risk or family history. The authors cite numerous risks, and it is NOT recommended.

Three cases are studied:

1.         Request for preventive mastectomy of patients with mutation or at high risk.
2.         Request for contralateral preventive mastectomy in these mutated or high-risk familial patients who have had first breast cancer.
3.         Request for preventive mastectomy in patients who have had breast cancer without genetic background.

Lesions referred to as "at risk"

These are "borderline" lesions found on microscopic examination after a breast biopsy, which are not benign, which are not cancers in the strict sense of the word, which are said to be "intermediate" and which present a more or less increased risk for the patient of turning into cancer later on.

Below are two tables of recommendations found in the literature that quantifies risk based on a biopsy result.
These two tables indicate the proposed course of action (abstention, surgery, or monitoring).

10 February 201723 February 2022

What if I don’t get screened?

The promise that regular screening would allow women to anticipate breast cancer before it occurred has reinforced the myth that healthy women require a scheduled test, breast cancer screening, to save their lives.

However, counter-intuitively, breast cancer screening can result in iatrogeny (medically induced illness), unnecessary diagnoses, and fears of a disease that will not necessarily occur, even if not screened, a route some women choose.

What about "doing nothing?"

Screening should remain a personal choice

This article does not concern women with genetic or familial risk because they often have a personalized and specialized follow-up. These are specific cases [1].

Women aged 50 to 74, in good health and with no personal history, invited for screening every two years, need to know that the invitation is optional and not urgent. Women can take the time to think about it and, most importantly, to obtain information.

If you are in this situation, you can make your personal choice, which may be based on knowledge and information you already have about breast cancer screening.

If this is not the case, and you have legitimate concerns about the benefits of participating in this screening, you can make your decision with the help of a "decision-aid tool" that presents you with the benefit/risk balance of screening, as examples can be found on the Cancer Rose homepage.

This decision varies from one woman to another, depending on their values and preferences, personal experiences, beliefs, and, most importantly, the value each woman places on the benefits and risks that a neutral and objective decision-aid exposes to her.
During the consultation, the health care professional should assist you in using and understanding the decision-aid and explain the items that appear on it without influencing you.
The terms 'mortality'[2], 'overdiagnosis'[3], and the consequences of 'overtreatment' should be explained to you, as should the term '5-year survival'[4].

Again, shared decision-making is influenced by the relative importance you place on the potential benefits and harms of screening. This is the tool's goal that will be available to help with shared decision-making.
If you choose not to be screened, it is essential to remain vigilant (this is true for all women, regardless of age) about any symptoms that may occur in the breast and which should, of course, lead you to seek medical attention.

All women must understand that screening is not the same as prevention.
In general, physical activity, avoiding excessive alcohol consumption, and not smoking are reasonable recommendations for better health and lowering cancer risk.

This is a very personal decision

To participate or not to participate? First and foremost, this decision is not final; you can change your mind.

Some women adopt a "do nothing" attitude, which is not as extreme as it appears, given that most breast cancers respond well to treatment, even when they have progressed through the organ sufficiently to manifest as a symptom.

Lung cancer and cardiovascular disease kill more women each year than breast cancer. Still, no public awareness campaign encourages women to get regular check-ups to detect these diseases early.
Given the uncertainties surrounding the efficacy of breast cancer screening, independent scientists and researchers recommend that women pay attention to and be watchful of this easily accessible organ, the breast, and encourage them to consult when they notice something is wrong, without becoming so compulsive as to seek out things that do not exist.

Decision aids, which are illustrated representations of numerical results for better understanding and memorization, should be used during a medical consultation to allow the woman to make an autonomous and personal decision.

There is no "correct" answer to the question "should I get screened ?" No one knows better than the woman herself, assuming she is well informed. The health care provider's opinion has no place in this decision.

What is at stake?

Not taking part in organized screening does not imply that you are careless, irresponsible, or unwilling to take charge of your health or that you do not care about your health at all.

This simply means choosing a different approach to care based on vigilance and quick response in the event of symptoms. There may be a slight (but not significant) loss of earlier diagnosis with this alternative strategy, but this is offset (primarily) by a substantial reduction in unnecessary treatments and their side effects.

This approach is known as "early clinical diagnosis," It is described in detail in an article [5]. Whether or not they have been screened, all women should be aware of changes in their breasts and consult a doctor if they notice any changes or the appearance of a symptom.

What we know:

There is significant uncertainty about the benefit of screening in reducing breast cancer mortality. [6]
The value of screening is further questioned because current breast cancer therapies are effective: whether detected by screening or not, breast cancer has a high chance of being cured.
Screening causes anxiety (false alarms) [7].
Screening does not prevent breast cancer from occurring after a mammogram (interval cancer), resulting in false reassurance [8].
There is a significant proportion of overdiagnosis [9], a well-known and recognized harm of screening.
Cancer survival [10] is the same in screened and unscreened women.
Contrary to what they are made to believe, for screened women, interventions (surgery, radiotherapy, chemotherapy) do not decrease [11]
The biology of cancer itself, the presence of aggressive biological characteristics inherent in cancer, not what a woman does or does not do to find it, will determine whether cancer will kill its host. An advanced tumor is not the "fault" of a woman who did not get screened but rather of the nature of cancer itself. [12]

So, what should women do in the meantime?

According to Pr. M.Baum, professor emeritus of surgery and professor, some recommendations can be given to women as stated in his book "The History and Mystery of breast cancer".

-The risk of breast cancer can be reduced by keeping the weight down, taking exercises, eating lots of fruits and vegetables, and keeping alcohol intake down to no more than 7 units a week ...

-M.Baum recommend not to ritualize Breast Self-Examination, but to be aware of changes in the breasts such as the chance appearance of a dimple in the breast, distortion of the nipple or feel a lump. In this case, says the author, an appointment with your doctor has to be made. M.Baum : "don’t look upon it as an emergency but for peace of mind don’t postpone the visit for too long".

-It is important to remember that there is more to life and death than breast cancer. The author asserts that breast cancer no longer ranks in the top 5 causes of deaths for women. Women should consider the totality of their health and how to avert a premature death from more common conditions (like heart diseases, editor's note).

-Furthermore, as M.Baum says, we could aim identifying a subgroup of women with a high risk of breast cancer; so we could offer them treatment that avoid the toxicity of radiotherapy (eg TARGIT/IORT).

Health Policy

Health Policy Policymakers implementing national cancer control plans must be aware of serious gaps in data that are frequently presented to them as unquestionable.

It is complicated to provide women and society with consensus-based information about the harms and benefits of breast cancer screening in the context of ongoing incentives to women each October and a scarcity of adequate information available.
The alternative is to educate the public about the differences that exist and, in any case, to allow women to make their own decisions.

If policymakers want to respect the principles of nonmaleficence and medical ethics [13] [14], they must consider that it is not screening participation rates that must be improved, but rather individual informed consent, which requires not only complete information on the problem but also the format in which this information is presented, without overemphasizing the benefits of breast cancer screening.