What is radiotherapy ?

Radiotherapy is the administration of radiation in order to destroy cancer cells and prevent them from multiplying. It must be targeted to avoid damage to the vital organs around.
Radiotherapy for breast cancer, which follows very frequently the surgical treatment, can nevertheless cause side effects, which may not be revealed until later. These effects may be local, directly affecting the irradiated organs, or general, and of variable expression depending on the sensitivity of the individuals.

-Local effects, more or less late :

Cutaneous effects, simple redness even radiodermatitis.

Pulmonary fibrosis causing the lung tissue to lose its elasticity.

Coronary heart disease, heart rhythm disorders, heart troubles, congestive heart failure.

Radio-induced secondary cancers, on the oesophagus, lung, skin, ribs.


-General effects :

Fatigue

Anaemia

Inappetence

Decrease in the number of blood cells

INDIVIDUAL RADIOSENSITIVITY

Another insufficiently addressed problem of radiotherapy for breast cancer is the uneven radiosensitivity among women. The breast is a highly radiosensitive organ, and repeated breaks in the DNA strands contained in breast cells can lead to mutations over time and can lead to secondary, treatment-induced cancers. However, this effect occurs in a variable way depending on whether one is radioresistant or moderate or hyper-radiosensitive.

The fact is that 25% of the population has this hypersensitivity to radiation which predisposes them, due to a deficit in their cellular repair mechanisms, to increased mutations and potential secondary radiation-induced cancers.

As explained above, radiotherapy treatments for breast cancer, which deliver repeated doses per session and over several sessions, are of course targeted at best, but there is a risk of radiation-induced cancer beyond the targeted area, especially if one belongs to the 25% of people who are particularly vulnerable to radiation. In spite of the very high individual variability, therapists continue to administer the same doses for all, without any testing to predict the individual radiosensitivity of patients. However, these tests do exist, and it would be urgent to inform patients about the existence of these tests to assess their own radiosensitivity, as not all tests are of equal value, and to obtain reimbursement for the scientifically proven tests.

Read more: Predictive Test for Radiotherapy Reactions: Women at High Risk

And: Radiotoxicity and breast cancer screening: caution, caution, caution…

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.

What is mastectomy ?

A mastectomy is a breast ablation. It can be partial (only the affected part is removed), or total (the entire breast is removed), when the tumor is too large in relation to the volume of the breast, when there are several lesions, or in the retro-areolar forms.
Advocates of breast cancer screening argue that with the detection of smaller lesions, there is less aggressive treatment on women's breasts, and therefore less heavy surgery is performed. However, several studies and particularly meta analysis have shown the opposite.
(A meta-analysis is a method of combining the results of several independent studies on the same topic in order to synthesize the results and draw an overall conclusion.) Furthermore, the independent review Prescrire, the meta-analysis by the Nordic Cochrane research group, the publication by Pr P. Autier and the american Harding study all report an increase in the number of surgical procedures. The more we detect, the more breasts are removed.


We have verified this ourselves with our study on mastectomies in France, which you will find in its completeness as well as the explanations on the site. Its results are indisputable: no reduction in mastectomies, total or partial, can be demonstrated after the generalization of organized screening.


Irrespective of this fact, what is at stake for women is not to promise them "lighter" surgical acts, but rather not to have them undergo any surgical treatment if they do not need it, while not exposing them unnecessarily to a disease which they should never have known in the absence of screening (over-diagnosis).

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.

What is chemotherapy ?

Chemotherapy is a therapy that uses chemical substances that have cellular toxicity, to affect sick cells in order to destroy them. Quite often several substances are combined to increase their effectiveness, especially if the cancerous disease spreads. The different drugs can be administered by intravenous injection (infusion) or orally (tablet). The molecules affect the diseased cells, but unfortunately also the healthy cells indiscriminately, which often causes more or less pronounced side effects, depending on the individual sensitivity of the person (loss of appetite, loss of hair, nausea, vomiting, severe fatigue).

Regarding breast cancer, since the screening was introduced, i.e. over the last thirty years, the percentage of patients undergoing chemotherapy has risen from 20% to around 80%. Chemotherapy for breast cancer also has effects on survival, comfort of life and other morbid effects for these treated patients.

Researchers warn on the over-detection of cancers that would never have impacted the lives of patients if they had not been discovered (over-diagnosis); the consequence is over-treatment, wherever screening is done, the number of mastectomies, radiotherapies (see relevant chapters) and chemotherapies have increased. All cancers that have been detected, real cancers as well as those that would not have progressed, are treated.
Scientists warn on the increased mortality due to over-treatment, and several studies suggest that the toxic effects of the treatments administered cancel out the hypothetical benefit of screening, which has already been widely questioned.

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.

LETTER of 4 Collectives on the subject of MyPEBS study

What is the MyPEBS study?

https://cancer-rose.fr/my-pebs/wp-content/uploads/2019/12/MyPEBS-Protocol-.V1.2-du-27.07.18-.pdf


MyPeBS is a clinical trial which compares the incidence of advanced breast cancers in a group of women subjected to breast cancer risk-based screening tests and in a control group undergoing current standard planned screening tests.Stratified screening on risk factors is an interesting project in itself, and carrying out a clinical study can only be favorable in order to confirm whether it is or not.


This study, however, would have to be carried out with appropriate methodology, which appears not to be the case of MyPeBS.


1st point: the choice of using standard screening as a control arm is contestable.

Three options can be considered for future screening programs: changing to stratified screening tests, continuing current standard screening tests, or discontinuing all screening tests. Comparing the stratified screening arm to a current standard control arm could hopefully provide the answer to the question: is stratified screening more efficient or less efficient than standard screening? The answer to this question would only enable to make a choice between changing to a risk based strategy and continuing with the standard screening strategy. It will not provide any additional information to enable to make a choice between screening; stratified or standard, and no screening.
It is all the more regrettable that planned screening does not seem as adequate in 2018 as when it became the standard strategy. In terms of benefits, the 20% relevant mortality risk reduction is based on old studies and has not been found in recent studies. In terms of risks, overdiagnosis has possibly been underestimated, as recent studies have evaluated it nearer to 40% than to 10% as initially forecast. It should not be forgotten that overdiagnosis = unnecessary treatment, side effects - sometimes serious- with no benefits in return.
MyPeBS therefore represents a missed opportunity: the opportunity to provide the answer, with current data, to the question: should planned screening tests be discontinued, be continued or be changed to risk-based? To achieve this, including 3 arms in the study: one risk-based screening arm, one standard screening arm, and one with no screening would have been sufficient.
Of course this would mean accepting to reconsider the importance of screening if the study did not demonstrate superiority of screening compared to no screening. The sponsors of MyPeBS do not appear to be ready to call into the possible question.


2nd point: a lax approach as to non-inferiority.


The main objective of MyPeBS is to demonstrate non-inferiority of risk-based screening, as compared to standard screening. Contrary to what one might believe, A non-inferior to B does not mean that A is at least as performant as B. A non-inferior to B, means in effect that A can be inferior to B but that this inferiority does not exceed a certain threshold.`
In the case of MyPeBS, this threshold of non-inferiority is set, arbitrarily, to -25%. In other words, it is easy to think that at the end of the study, risk-based screening is certainly less performant than standard screening with, for example, performance loss somewhere between -5 and -20%; however, as the performance loss does not reach -25%, non-inferiority is confirmed, when in fact at best, the loss is of -5%, and at worst, this performance loss could reach -20%. Supposing your employer were to inform you that your salary scale was going to be revised downwards or upwards. Would you be truly reassured if your boss specified that in any case, if your salary were to decrease, this decrease would not be inferior to -25% ?And would you consider that a decrease of -25% of your income is insignificant? Well, this is exactly what MyPeBS puts forward. Simply replace “employer” by “study protocol” and “salary” by “screening efficiency”.


3rd point: deceitful information.

In the information leaflet, large-scale studies which showed that screening had reduced the mortality rate of breast cancer by around 20% are mentioned in the part of the text “Advantages and disadvantages of standard breast cancer screening”. Indication that those studies are old and probably obsolete or that a significant decrease of mortality by screening has not been found in recent studies [1,2] has been carefully omitted.
Concerning overdiagnosis, the leaflet merely mentions 10%, failing to specify that the frequency of overdiagnosis is not well known, with rates of up to 50% in some studies [3,4]. Furthermore, there is no mention of overtreatment that occurs with overdiagnosis. Nevertheless, they are indeed unnecessary treatments, with multiple side effects, which represent the major risks of screening tests.
Present scientific uncertainties make the presentation of benefits and harms of screening difficult. However, no information should be withheld, or for the purpose of clarity, should only convenient statistics be presented and others overlooked.
Studying the interest of stratified screening on risk factors might seem useful, but not haphazardly and certainly not with the main intention of promoting mammography screening one way or the other. This intention is clearly mentioned in Dr Balleyguer’s statement, page 14 in the press folder MyPeBS, 28 September 2018: "MyPeBS will probably encourage more women to enter national screening programs. Today, barely one out of two are taking part” [5 ].

READ MORE :
https://cancer-rose.fr/my-pebs/2019/08/02/mypebs-clinical-trial-failed-before-starting-2/

In response to these concerns

In response to these concerns, 4 European collectives, militating for independence in health, published an open letter, here is the English version:
https://cancer-rose.fr/my-pebs/wp-content/uploads/2020/02/LETTRE-COMMUNE-ANGLAIS.pdf

This letter was picked up by the press and mentioned in an article of the BMJ.

Press feedbacks


Article JIM
Article Quotidien du Médecin du 12 mars 2020 (french)
Article BMJ


Extract from article BMJ


The groups criticise the trial for assuming that breast screening is beneficial and for failing to compare stratified screening with a “no screening” group.
“MyPeBS represents a missed opportunity to provide the answer, with current data, to the question: should planned screening tests be continued, be changed to risk based screening, or stopped?” they wrote.
They also raise concerns about the trial’s “lax approach to non-inferiority” and point out that the two groups will be statistically compared with a threshold of “non-inferiority” arbitrarily set at 25%.
They go on to explain, “This comparison is obscure and conceals disconcerting information. According to the sponsors of MyPeBS, in the standard screening group, 480 new cases of severe tumours per 100 000 women are expected to be diagnosed. If the same rate does not exceed 600 per 100 000 women in the new personalised risk based group, both groups
will be declared equivalent. This means that if the rate of serious cancers is increased by less than 25% (for example 18% or 24%), then the study will be considered a success and the researchers conclude that the new screening methods are ‘as efficient’ as the former ones. In other words, +25% of serious cancers equals zero.”
Karsten Juhl Jørgensen, acting director of the Nordic Cochrane Centre and an author of the Cochrane review on breast screening, said that screening trial data were old, women below the screening age had experienced far greater reductions in breast cancer mortality than those invited, and new treatments have a far more important role than screening.
Jørgensen told The BMJ, “We desperately need a new trial of screening that can inform us about its role today. Whether personal screening strategies can optimise benefits and reduce harms is an important and relevant question. But screening trials need to be done extremely well to be informative, part of which means not relying on surrogate outcomes such as stage at detection, which we know can be misleading. The design of the new trial seems to raise more ethical questions than it answers.”

Ref.

  1. Autier P., Boniol M., Koechlin A., Pizot C, Boniol M. (2017), Effectiveness of and overdiagnosis from mammography screening in the Netherlands: population based study. BMJ 2017;359:j5224 (https://www.bmj.com/content/359/bmj.j5224)
  2. Møller M.H., Lousdal M.L., Kristiansen I.S., Støvring H. (2018), Effect of organized mammography screening on breast cancer mortality: A population-based cohort study in Norway. Int J Cancer. (https://europepmc.org/article/med/30144028
  3. Junod B., Zahl P.-H., Kaplan R.M., Olsen J., Greenland S. (2011), 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.(https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-11-401)
  4. Welch H.G., M.P.H., Prorok P.C., O’Malley A.J., Kramer B.S. (2016), Breast-Cancer Tumor Size, Overdiagnosis, and Mammography Screening Effectiveness. N Engl J Med 2016; 375:1438-1447. (https://www.nejm.org/doi/full/10.1056/NEJMoa1600249)
  5. http://www.unicancer.fr/sites/default/files/MyPeBS-DP.pdf

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.

The largest clinical trial in Great Britain on breast cancer screening was halted

https://www.bmj.com/content/370/bmj.m3337.full

Summary by C. Bour, MD

27 August 2020

A major UK breast cancer screening trial called AgeX [1], was halted, more exactly inclusion and randomization of new participants will not resume.
Age X is the acronym of the trial founded by British Gouvernment: it is a controlled randomized trial set up to expand the age bracket determined by NHS (National Health Service) for the breast cancer screening in UK.

The trial investigates the incidence and mortality from breast cancer in different groups and aims to evaluate the risks and benefits of expanding mammography screening for breast cancer beyond the current age range of 50 to 70 years by providing an additional mammogram to women aged 47 to 49 and up to 73 years of age. Announced as "probably the largest randomized controlled randomized trial ever performed in the world," AgeX has randomized 4.4 million women to date in the expanded age groups.
Normally, the goal was to recruit a total of 6 million women in the trial in order to ensure statistical significance and draw conclusions.

This trial had generated a strong scientific controversy on both methodological and ethical arguments when it was set up in 2009, as the women included in the trial were unaware that they were part of it.

The contesting was brilliantly led by the HealthWatch UK site under the chairmanship of Professor Susan Bewley, but also by medical author Mitzi Blennerhassett and independent scientific editor Mandy Payne.[2] [3]

Here we have summarized the entire issue [4], the authors pointing first and foremost to the omission of the informed consent of participating women.

They also denounced the fact that screening does not demonstrate sufficient evidence of effectiveness, but instead, it can be harmful for women who are not fully aware of all these risks, and that the number of mastectomies could increase with the inclusion of more women, which were also uninformed.

Finally, to make sure of the informed consent of women in the AgeX trial as well as in all screening programs, Susan Bewley, Mandy Payne and Mitzi Blennerhassett requested the National Screening Committee to use high-quality text boxes and charts with visual pictograms.
They asked investigators and auditors of all data resulted from AgeX trial, to use the rate of death for “all-cause” as main result. Then finally, they called for an independent investigation of the scientific quality, governance mechanisms and ethical issues arising from this trial in order to identify future high quality standards for the design and execution of future government-sponsored trials.

Discontinuation of the trial

The trial was halted alongside other screening services to allow the NHS to cope with covid-19 [5].
The researchers have announced that randomization will not resume.
However, they said that follow-up by electronic linkage to routine government records will continue “throughout the 2020s and beyond.”
The AgeX website [1] now says, “Following the suspension of routine breast screening throughout the UK in March 2020 due to COVID, and the substantial and prolonged overload on breast screening services to be expected when screening restarts, the AgeX investigators decided in May 2020 that further randomisation into AgeX should cease permanently.”
The trial’s team said : “Although the intent had been to continue until about 6 million had been recruited, 4.4 million will, with sufficiently long-term follow-up, suffice”

The contesting continues, an inquiry is requested

Commenting on the trial, M.Blennerhassett said, “Having sat on a local research ethics committee, I was shocked that this trial had been approved. When I raised concerns my questions were not answered. I was simply referred to the NHS Breast Screening Programme website which, at that time, had no information regarding the trial.”
Susan Bewley told The BMJ, “Although covid will be credited with ending AgeX, this trial would not have stopped prematurely with no fanfare were it actually answering a necessary research question that had been through proper channels of peer review and funding.
“This largest randomised controlled trial in history has been criticised for having no statistical plan or oversight at onset, and repeatedly changing protocol, numbers, and endpoints. Four million women have already taken part in this unethical human experiment, without having had their understanding checked and giving their explicit informed consent.”
Susan Bewley has called for an independent inquiry “to learn the lessons of this government funded research, sponsored by the University of Oxford, and approved by the Human Research Authority that rode roughshod over women’s rights for a decade … We need to ask the question: who approved this, and how much did it cost?”

Références

[1] http://www.agex.uk/
[2] https://www.healthwatch-uk.org/projects/breast-cancer-screening-age-extension/122-age-extension-trial-of-mammography-screening-part-5-april-2019.html
[3] Bewley S, Blennerhassett M, Payne M. Cost of extending the NHS breast screening age range in England. BMJ 2019;365:l1293. doi: 10.1136/bmj.l1293 pmid: 30971394
[4] https://cancer-rose.fr/2019/04/10/3924-2/
[5] National Health Service

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.

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].

Read more about:

The international reactions to attempts to cover up screening failure in a publication

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.

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.

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

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.

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.

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.

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/

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.

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

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.