Cancer regression

June 25, 2020, summary by Cécile Bour, MD

G. Welsch, professor at the Center for Surgery and Public Health Brigham and Women's Hospital proposes an analysis of breast cancer screening by MRI in an educational video, using data from the "DENSE" trial (results published in 2019), with the reservations (see comment at the end of the article) that were expressed after the publication of the results in the NEJM.

What is this trial?

This is a randomized trial, of good quality.

Explanation of the method on the video at 1:12 video.

The researchers divide 40,373 women aged between 50 and 75 years of age, with extremely dense breast tissue and negative results on the initial screening mammogram, into two groups: in the " supplementary MRI" group or in the "screening mammogram only" group; more precisely 8,061 women in the "MRI invitation" group and 32,312 women in the "mammogram only" group.

A control mammogram is then performed for both groups after two years  in order to compare the results on the number of cancers found.

The main finding was the difference between the groups in terms of incidence of interval cancers over a two-year screening period.

Additional MRI screening appears to be associated with fewer interval cancers compared to mammography alone in women with extremely dense breast tissue.

Specifically, the researchers found that the interval cancer rate was 2.5 per 1,000 screenings in 4,783 women in the MRI invitation group compared to 5 per 1,324 women in the mammography alone group.

However, in the analysis of these results, one important element is missing, according to G.Welsch: the exhaustive counting of all cancers in both groups.

The fact that there are more cancers in the screening-MRI group compared to the non-MRI group suggests that there are more detections with MRI. But this finding may also suggest something else, supporting the theory of variable kinetics of breast cancers: all cancers do not have same expression pattern, some of them possibly regress.

Regression of cancers?

We remind that this is a randomized trial. Since women are randomly assigned to one or the other group, it is expected that after two years we should have the same overall cancer rate in both groups.Video at 2:03

Cancers not anticipated by screening in women from the group without MRI would be necessarily expected to express themselves at the end of two years on the mammogram performed for both groups at the end of the study.

What is actually observed?

 - No cancer found at the initial mammogram in either group.

 - Globally more cancers found in the MRI group

- Fewer interval cancers in the MRI group

- At the end of the two-year control mammogram for end of the study, more interval cancers in the non-MRI group, as they were not anticipated by MRI.

 - Fewer mammographic cancers at the end of two years for the MRI group since a fraction is anticipated on MRI.

===> In total, we get an excess of 5.4 cancers found in the MRI group (Video 3:34)

G.Welsch explains: in a randomized trial with two random distribution groups, what is expected is that at the end of the study we will have a similar 'total cancer' rate, since cancers not anticipated by MRI in the non-MRI group are logically detected later on the control mammogram done at the end of two years.

The picture illustrates the group of women screened with additional MRI on the left and the control group without MRI on the right. We see in the red column all the cancers detected by MRI resulting in an excess of detection; the green squares indicate the interval cancers which are more present in the group without MRI as they were not anticipated by this examination; the yellow squares symbolize the cancers seen two years later on the mammogram at the end of the trial which are more numerous in the women without the anticipatory MRI. Nevertheless, a comparison of the 'total-cancers' of the two groups clearly shows an excess of cancers for the group with additional MRI.

Now, what happened to those 5.4 excess cancers not found in the non-MRI group, are they cancers that will appear later?

Or have they disappeared?

In general, the explanation put forward is the hyper-slow growth of these cancers, which do not appear during mammography at 2 years of age, not progressing or very very slow  progressing. This would mean that more than half of the cancers found by MRI are hyper-slow-growing cancers so that they are undetectable on mammography. Reminder at 3/30 of the video: we find in the trial 9.8 cancers in the MRI group, 5.4 excess cancers /9.8 total cancers in the MRI group = 0.5

The alternative explanation exists, and it is the cancerous regression, namely the disappearance of these cancers not found on the mammogram for control after two years. They simply disappear. (Editor's note: this hypothesis also emerges from the 2008 Oslo study, where the group of women screened every two years had a 22% excess of cancers detected over the group of women not screened, the two groups being compared after 6 years with a mammogram performed for each group.)

However, if all cancers were inexorably progressing and were expected to manifest themselves, the same number of cancers should be found at the end of the 6-year observation period in regularly screened women and in the non-screened women, in whom the cancers not detected by previous screenings should then be seen on the mammogram at the end of the study, at the end of 6 years. If this is not the case and there is an excess of cancers in the screened group, it is likely that some cancers that did not occur in the unscreened women have disappeared in the meantime.

Cancer regression is observed for other forms of cancer: kidney cancer (1/4 of cancerous lesions regress) of the thyroid (1/3 of cancerous lesions regress). So why not for breast cancer???

The benefit/risk balance

So let's consider the risk/benefit balance of increased MRI monitoring:

video: 6/08.

Overall, the results tends to suggest that the risks associated with increased MRI surveillance of dense breasts outweigh the benefits.

Good news and bad news

There are  good news when it comes to breast cancer. Since the 90s breast cancer mortality has dropped by 40% (i.e. already before the arrival of national screening campaigns, editor's note).

This is an important reduction, according to G.Welsch who reminds us that this drop in mortality is due to therapeutic advances, and not to screening.

Video: 6:20

The bad news according to him is that screening is the target of a technological weapons race, since the first analog mammography, then mammography, the arrival of 3D (tomosynthesis) and now the advent of MRI, all aimed at finding more cancers. For what benefit?

Conclusion of the author

The challenge is not to find more and more cancers inducing unnecessary over-treatment, but to detect those cancers that are important to find because they are a threat to a patient's life.

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 over-diagnosis, in a graph and a table

December, 3, 2016

Here you will find a representation on a poster (home-made) of the results of meta-analyses from the independent French medical magazine Prescrire, the Cochrane Collaboration (a collective of independent Nordic researchers) and the US Preventive Task Force, the US public health program evaluation agency.

Despite some variations in the data, there are two standout points : on the one hand, the estimates are reasonably close, on a proportional basis, and on the other hand, for each of these three studies, there is a much higher proportion of overdiagnoses and false alarms compared to 'avoided' deaths, pointing out the disadvantages of screening. The benefit/risk balance is therefore far from being as optimistic as it is presented to women…
The Cochrane presents its results on 2000 women screened from age 40 onwards over 10 years,
Prescrire on 1000 women screened from 50 years of age over 20 years,
US Task Force on 1000 women also, screened from 50 to 74 years old, which corresponds most closely to the French situation (click to enlarge).

The brown dots represent the number of women screened and then monitored. The red dots correspond to over-diagnoses, the yellow dots to the number of cancers presumably prevented. The light blue dots are false alarms, and the dark blue ones are unnecessary biopsies.
Here we reproduce a very meaningful graph showing how over-diagnosis occurs, based on the idea of an American researcher, Gilbert Welch, adapted here by Dr. Jean-Baptiste Blanc and with his kind permission to reproduce this image.
Click on the link to read Dr Blanc's article "deconstruction of a manipulation".

Rapidly evolving cancer progresses fast between two mammography examinations and will be "missed" by screening. Often this cancer will have already spread to distant nodes and organs, even though it is not visible.

  • Slowly evolving cancer will certainly be anticipated by screening, but even without screening it will be detected a little later by the appearance of clinical symptoms that will lead the patient to consult in time, as the metastatic time is very long.
  • For the other three forms of cancer, the very slow, not evolving and regressing cancer, screening will detect them but this is a needless detection, the women in whom they have been diagnosed would have died with their cancer but not because of it.

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.

Less is more medicine

The challenge of implementing of Less is More Medecine : a European perspective

26 May 2020

Authors : Omar Kherad Nathan Peiffer-Smadja Lina Karlafti Margus Lember Nathalie Van Aerde Orvar Gunnarsson Cristian Baicus Miguel Bigotte Vieira António Vaz-Carneiro Antonio Brucato Ivica Lazurova Wiktoria Leśniak Thomas Hanslik Stephen Hewitt Eleni Papanicolaou Olga Boeva Dror Dicker Biljana Ivanovska Nicola Montano

Summary of the article : Cécile Bour, MD

The concept of Less is More [1] medicine emerged in North America in 2010. It aims to serve as an invitation to recognize the potential risks of overuse of medical care that may result in harm rather than in better health tackling the erroneous assumption that more care is always better.
In response, several medical societies across the world launched quality-driven campaigns (“Choosing Wisely”)[2] ) and published “top-five lists” of low-value medical interventions that should be used to help make wise decisions in each clinical domain, by engaging patients in conversations about unnecessary tests, treatments and procedures.

The purpose of this article is to analyze the conditions and obstacles to the launch of a similar European initiative aimed at reducing the overuse of medical procedures that are currently identified as unnecessary and even harmful in daily practice. Therefore, such a program may lead to a reduction in the cost of health care, although the authors emphasize in their conclusion that this is not the primary objective, but a beneficial corollary effect.

The authors of the article also identify obstacles and challenges to the implementation of Less is More in several European countries, where overmedicalization is culturally rooted and required by a society that demands health certainty at almost any cost.
High expectations of patients, medical conduct, lack of follow-up and pernicious financial incentives all have more or less direct negative effects on over-medicalization.

To implement the Less is More recommendations on a large scale, multiple interventions and evaluation efforts are needed.

These recommendations consist of a top-five list of actions:
(1) A new cultural approach from medical school graduation courses, up to
(2) patient and society education,
(3) physician behavior change with data feedback,
(4) communication training and
(5) policy maker interventions.
In contrast with the prevailing maximization of care, the optimization of care promoted by Less is More medicine can be an intellectual challenge but also a real opportunity to promote sustainable medicine.

This project will constitute part of the future agenda of the European Federation of Internal Medicine.


Access almost universal to quality health care is one of the hallmarks of the "European model", but how can we ensure the sustainability of European healthcare systems in an era of aging populations and budget restriction?
Financial aspects should be taken in account, as avoiding unnecessary practices have become a priority to ensure quality and access to care for everyone in the long term in both poor as well as wealthy countries!
A major concern has been not to miss a disease, to avoid problems of underdiagnosis and undertreatment. This has been supported by sustained and powerful technological growth and we are now facing the other side of the coin.
This results in: too many drugs, too many tests, too many screenings, eventually becoming a threat with accumulating evidence of over-diagnosis itself leading to damage from unnecessary treatment.
Following this dual perspective, with both qualitative (patient safety and avoidance of low-value, ineffective care) and quantitative aspects (costs), a new trend emerged in medicine: Less is More.


Several medical societies across the world launched quality driven anti-waste campaigns such as Choosing Wisely in US, Smartermedicine in Switzerland, Slow Medicine in Italy, SMART Medicine Initiative in Israel, and Choosing Wisely in UK, France, Belgium, Portugal, Romania, Russian Federation and Poland.
These societies published “top-five lists” of low-value medical interventions which should be avoided [3]

But the concept of Choosing Wisely is applicable to the screening.
The article evokes the aspect of Less is More in this field.


The key mechanism for change lies in creating a shared decision-making process between physicians and patients during routine clinical encounters.
Physicians are often reluctant to speak about overdiagnosis. Most participants in a US cross-sectional online survey who underwent routine cancer screening reported that their physicians did not tell them about overdiagnosis and overtreatment [4].
The few who received information about overtreatment had unrealistic beliefs about the extent of that risk.

We have discussed this point here : perception and reality
Both benefits and harms of action or inaction must be discussed in order to help make better decisions about clinical situations in which care is needed.
Clinicians and patients must share the responsibility for the final decision, as both parties experience the potential consequences.

A 2015 article[5] shows the level of over-detection that people would find acceptable in screening for breast, prostate and bowel cancer, and attempts to see whether the screening acceptance is influenced by the magnitude of the risks.
This survey illustrates the varying level of acceptance depending on the level of information of individuals and suggests that clear information should be included in invitation letters for screening.
The whole Choosing Wisely campaign is patient-oriented and promotes shared decision making.
That means using personalized assessments of potential benefits and harms, as well as considering the preferences of patients who are well informed about possible options. The interaction between patients and doctors must be strengthened because a good therapeutic relationship can cause the decrease of the unrealistic patient expectations which can cause overconsumption.
The Choosing Wisely campaign can help “educate” patients (meaning an education for comprehension of medical data) and explain them why an unnecessary test may be harmful so that doctors and patients can have more constructive conversations about the tests.

The dimension of healthcare costs is addressed more widely in the Anglo-Saxon countries than in France[6], in a relevant manner, as savings from unnecessary medical care can be put to good use in other areas (Editor’s note).


  1. Patients’s expectations
    For decades, the idea that seeking medical care is the key to maintaining well-being and that more medicine is better than less has been sold to patients.
    There is an enthusiasm for early diagnosis as part of preventive strategy, as this allows patients to feel heard and reassured.
    However, negative consequences of false positive diagnostic tests are underestimated. In addition, patients have huge expectations of their expensive health care system, and often bristle at recommendations that seem to limit their choice: any attempt to limit the access to doctors might be interpreted in relation to its economic dimension, raising fears about “rationing”.
    Moreover, the principle Less is More is frequently counterintuitive, too (for both physicians and patients), and because of this it is psychologically hard to accept.
  2. Physicians’s behaviour
    Some tests are ordered out of fear of missing a diagnosis. Cognitive biases, such as anticipated regret for missing a diagnosis, and commission bias, or the tendency toward action rather than inaction, lead to performing more tests. The fear of being sued for malpractice is of major importance, particularly in the US, where three-quarters of physicians report practicing defensive medicine, though “defensive” medicine is becoming more popular in Europe as well.
    An example is given [7] with the prescription of PSA test, despite the current non-recommendations for systematic screening of prostate cancer in men.
    In case of medical error, a physician who was exhaustive in patient care is less likely to be sued. This raises the issue of how physicians can balance the growing focus on patient satisfaction scores with the drive for evidence-based medicine. Some physicians are aware of the guidelines but disagree with the evidence and more broadly misunderstood the evidence-based medicine (EBM) approach. That’s true, some recommendations may rely upon biased studies or on experts opinion, thus far away from being “evidence-based” ….[8] We also have addressed this topic [9] [10].
  3. Other factors, which are barriers to reduce overuse of medical care, are detailed in the article, such as:
  • Sometimes insufficient evidence in some medical controversies,
  • Lack of research and lack of resources for research,
  • Fragmentation of care (e.g., moving from one care setting to another such as from a hospital to a specialized care facility, or simply from one physician to another increases the risk of care errors. New medications could be prescribed in duplicate or negatively interact with other treatments),
  • Difficult to measure the impact of less is more practice
  • Financial incentives (the fee-for-service system as in France, Switzerland or Belgium)
  • Lack of student education

In conclusion

There is substantial overuse of some common procedures that demonstrate no benefit and present potential harm in everyday practice, say the authors of this article. In order to reduce over-medicalization and maintain physician commitment and public confidence, it is necessary to avoid using cost as a motivating factor, and instead focus on unnecessary tests that may be harmful.
EFIM launched two years ago a “Choosing Wisely” project involving twenty- six national societies of Internal Medicine. The aim of this project is, first of all, to stimulate the dissemination of the low-value, high-value care concepts and the top-five lists from participating countries; secondly, to start educational programs for physicians, educators, residents and students using practical courses and publications, and thirdly, to design research tools to evaluate the effects of Less is More approach on appropriateness of care and cost reduction.

Our opinion

The approach described in the paper specifically concerns medication prescribing practices; we hope that the reflection on over-screening will also be widely included in the European program to reduce overmedicalization.

At present, unfortunately, the issue of screening, particularly for breast cancer, is much less scientific than it is cultural, social and political. Financial and ideological stakes burden this screening.
The process of choosing wisely, in terms of these abusively so-called "preventive" procedures, risks being very long and going through a patient public education, unfortunately countered regularly by a medical populism that is more and more present, like the deplorable and terribly deleterious for the science itself image, which we witnessed during the Covid-19 epidemic.



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.

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30,000 cancers overdiagnosed in an Australian study

30,000 cancers overdiagnosed each year in an Australian study : a public health issue

Summary , Cécile Bour, MD
28 January 2020
Authors of australian study published in Medical Journal of Australia
Paul P Glasziou, Mark A Jones, Thanya Pathirana, Alexandra L Barratt and Katy JL Bell
Med J Aust || doi: 10.5694/mja2.50455

The obsession of our modern societies to track diseases through ever earlier detection is leading to a public health crisis, according to Australian authors who published in January 2020 their evaluation of over-diagnoses for five different cancers.


National data routinely collected by the Australian Institute of Health and Welfare (Australia's national agency for health and welfare information and statistics) were analyzed to estimate risks in population to have a cancer during lifetime by comparing the current period (2012 data) with the past (1982 data).
This allowed to measure changes in these risks over the last 30 years. An adjustment has been made to take into account the risk of death and changes in risk factors over time.
The five different studied cancers are: prostate, breast, renal, thyroid cancers, and melanoma.

The authors propose an estimate of the proportion of cancer diagnoses in Australia which are reasonably due to over-diagnosis.


For women, an estimated 22% of breast cancers (invasive cancers, 13%), 58% of renal cancers, 73% of thyroid cancers, and 54% of melanomas (invasive melanoma, 15%) were overdiagnosed.

For men an estimated 42% of prostate cancers, 42% of renal cancers, 73% of thyroid cancers, and 58% of melanomas (invasive melanomas, 22%) were overdiagnosed.
Despite the relative uncertainty conceded by the authors themselves about these estimates, this result would be equivalent to an overdiagnosis representing about 18% of women's cancer diagnoses and about 24% of men's cancer diagnoses in Australia in 2012, i.e. about 11,000 women's cancers and 18,000 men's cancers overdiagnosed in Australia each year.

Absolute rates of over-diagnosis were highest for breast cancer and prostate cancer due to their higher baseline prevalence (rate of new cases + rate of cases already present).


The population is certainly aging, but screening programs are the big providers of overdiagnoses.
Cancer can also be overdiagnosed outside screening programs; for example overdiagnosis of thyroid cancer is attributable to incidental detection during imaging investigations of unrelated problems or the overdiagnosis of abdominal scans carried out for other causes.


Overdiagnosis is important to know and control because of the adverse effects on iatrogeny (pathology induced by treatments) and the associated additional costs.

Harms include the psychosocial impact of unnecessary cancer diagnoses, such as the increased suicide risk for men after being diagnosed with prostate cancer.
Cancer treatments such as radiotherapy, endocrine therapy and chemotherapy can cause physical harm, but the risks are considered acceptable if diagnosis is appropriate. Contrary, when someone is unnecessarily diagnosed with a cancer which would not be harmful for its health or life (overdiagnosis definition), this person will suffer harm as a result of the treatment, instead of enjoying the benefit of having been detected.

In other countries

This study is the first study to estimate overall cancer overdiagnosis on a national level.
A recent British analysis found that the “incidence of 10 of the 20 most common cancers in the UK has increased by more than 50% in both sexes since the 1980s.” These cancers included breast, kidney, prostate, thyroid cancers and melanoma, but also non‐Hodgkin lymphoma, oral, cervical, liver, and uterine cancers.
The authors therefore estimated overdiagnosis only for cancers with the typical epidemiologic signature of overdiagnosis: breast, prostate, kidney, thyroid cancers and melanoma (for which lifetime mortality has changed little in absolute terms).
UK cancer statistics released in January 2019 show very high survival rates for people with early stage cancers of these types, providing further evidence of probable overdiagnosis: 5‐year survival of 99% for stage 1 breast cancer, 100% for stage 1 prostate cancer, 100% for stage 1 melanoma, 89% for stage 1 kidney cancer, and 88% for thyroid cancer of any stage.

Editor’s note: Survival, often emphasized by INCa to justify the screening for breast cancer, is not an indicator of screening effectiveness, but a good over-diagnosis marker.
Survival measures the length of life with a cancer, If the cancer is not meant to kill its carrier, as is the case for cancers detected predominantly by screening, which are at low stage, survival can indeed be important since these cancers detected would never have led to the death.

The more over-diagnosis emerges, the more cancers that could have been ignored, and the better the survival rates, automatically.
The only appropriate indicator of the effectiveness of screening is mortality, or more precisely total mortality.

Author’s conclusion

Cancer overdiagnosis has important implications for health policy.
First, rates of avoidable overdiagnosis need to be reduced to the lowest level compatible with targeted screening and appropriate investigation, instead of mass screening.

Strategies to reduce overtreatment of low-stage, therefore low-risk prostate, breast and thyroid cancers should be addressed.

A second, and perhaps more important implication is that health services need to be alert to new areas of overdiagnosis and to detect them early.

Editor’s note: Australia has already initiated an over-diagnosis action plan : https:/

Editor’s note: The Australian example should prompt us to look downwards, in particular to the pink October commercial campaigns that culpably promote and train crowds to practice mass screening, encouraging women to be screened even outside the screening age range.

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.