ARC classification

ACR mammography classification

By Cécile Bour, MD, Radiologist

November 11, 2018

Testimony of the radiologist....

I was alerted by fellow general practitioners who rightly questioned the ACR classification in the conclusions of our mammogram reports, and who tended to draw a parallel between this scale and the seriousness or poor prognosis that their patient would have ...

The question is quite relevant, as we, radiologists happily classify our description in a sort of coded verdict, without really explaining the why and how of things and without realizing that for the correspondent it is not intuitive to know to what these ACRs correspond. Above all, there is a great risk of overlaying this classification of imaging alone with the classification of cancer severity stages.

However, the two have nothing to do with each other.

The ACR classification

ACR (American College of Radiology) classification was developed in 1990, due to the need of systematizing reports in order to harmonize practices. We find 5 stages which correspond to the more or less certainty of having to deal with a cancer in front of a mammographic image.

ACR 1: normal, the breast has " nothing to report ".

ACR 2: we have images that are only benign abnormalities, this includes small axillary nodes, micro cysts, images that are undetermined but have been strictly unchanged for ages, fibro-adenomas or cysts that are already well known and have been identified as benign (by ultrasound, MRI or previous biopsy), vascular, cystic or galactophoric microcalcifications, amorphous glandular islets etc...

ACR 3: this stage designates an image that is not very worrying but whose future is to be verified, which was not known before, or known but has changed slightly compared to previous exams. The standard proposed procedure for this classification is a single monitoring at 6 months, then at one year, to ensure that it does not increase in size or that the analysis criteria do not become more characteristic in favour of malignant lesions.

ACR 4 classification means that there is a high probability of cancer, and that it is a very suspicious abnormality to be sampled in any case. ACR4 therefore automatically implies a biopsy, under ultrasound (micro-biopsy) or under radiographic control, by a mammotome procedure (macro-biopsy), or directly by biopsy-exeresis. In the end, we may have made a misinterpretation, or it may be a poorly evolving cancer, or even a very aggressive cancer; the type of image that led us to classify it as ACR4 says nothing about the aggressiveness or not of the cancer, if what we biopsied is indeed one!

ACR 5: the anomaly is very strongly suspected of malignancy and the semiological criteria are quite evocative and typical of malignancy. We can say that we are very, very sure of the malignancy.

ACR 0 is the incomplete examination that will have to be added to other imaging examinations.

This description of the mammographic image determines the decision

Unfortunately, on the one hand it is very subjective. Not all "expert" readers always agree on whether to classify as ACR 3 or ACR 4.The switch from analog to digital mammography (a recent process which, I intentionally shorten and simplify, makes you see better and smaller things than the previous mammography process) makes it more complicated to compare an old exam done in analog to a "better" digital imaging.This will give the impression of an image with perhaps more irregular contours than before, or which would be denser, or slightly increased in volume, whereas it is simply the change in technique that induces this doubt, as the images of two different examinations are not strictly overlapping.

On the other hand, medico-legal issues have become more prevalent over time, as well as the increase of the overall level of anxiety for both the patients and the medical profession. The ACR3 classification is more and more abandoned in favor of the ACR4 which becomes an abominable bottomless pit into which the radiologist throws almost any image that does not let him sleep.

As we have already seen on this site[1] neither the specificity nor the positive predictive value of mammography are good.

Specificity is the probability that the screening mammogram will be negative for a subject (in this case the screened woman) who is not ill. However, the specificity of screening mammography is not sufficient, because the test may be positive in some cases when the woman is not ill.

Unfortunately, the double reading, practiced for the organized screening in France, presented as an improvement of the screening test, further decreases the already poor specificity of the mammogram, and at the slightest doubt the second reader will outperform the mammogram for fear of "missing" a cancer. In other words, the already poor specificity of screening mammography is further weakened by double reading.

The positive predictive value is the probability that the subject (the woman being screened) will be ill for a positive test. The PPV of screening mammography is very low, between 9 and 10%.

This means that for a woman for whom the mammogram is judged positive and for whom a biopsy of the incriminated image is performed, there is a 90% chance (100%-10% of PPV) that the biopsy will come back negative and therefore has been excessively proposed. As the journal Prescrire has pointed out, breast biopsies have literally exploded since the screening was performed. [2]

Conclusion

In practice, it is important to remember that radiological classification has nothing to do with the classification of cancerous stages, and that an ACR4 classification is not always based on a very dubious radiological semiology, but to a large extent because we want to identify the cancer by sampling very quickly, because a new image  that was not visible before has appeared, because an image may have changed or become a little bigger, because one does not want to give oneself the time to simply monitor, any diagnosis becoming abusively urgent and intolerable in the minds of professionals as well as the public. Contrary to what is taught to the public, there is no urgency or loss of chance to wait a few weeks, a few months... But this reasonable and wait-and-see attitude is no longer possible nowadays, especially after alarming public appearances of health authority officials or opinion leaders alerting people by the press or popular health programs that "we have no time to lose".

The level of anxiety in the population, already very high because the multiplication of these invasive gestures, misunderstood because they are poorly justified, it will further become even higher.

What makes us wonder is that in the new European MyPEBS trial, initiated to study the relevance of stratified screening based on risk, the fact of having had a biopsy, even a benign one, represents a risk factor for women that justifies classifying them as « being at higher risk than normal »...

See page 19/20 of the synopsis: https://cancer-rose.fr/my-pebs/wp-content/uploads/2019/12/MyPEBS-Protocol-.V1.2-du-27.07.18-.pdf

Well, being a woman is already a big risk...

Bibliography

[1] https://www.cancer-rose.fr/cancer-du-sein-un-peu-de-technique/

[2] Prescrire magazine, February 2015/Tome 35 N°376

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.

In situ carcinoma, Toronto study

Matthieu Yver, MD (Anatomopathologist)

Cécile Bour, MD (Radiologist)

Breast Cancer Mortality After a Diagnosis of Ductal Carcinoma In Situ (DCIS)

Treating ductal carcinoma in situ does not reduce mortality from breast cancer

http://oncology.jamanetwork.com/article.aspx?articleid=2427491

Autors : Steven A. Narod, MD, FRCPC1,2; Javaid Iqbal, MD1; Vasily Giannakeas, MPH1,2; Victoria Sopik, MSc1; Ping Sun, PhD1
JAMA Oncol. Published online August 20, 2015. doi:10.1001/jamaoncol.2015.2510

Treating ductal carcinoma in situ does not reduce breast cancer mortality, according to a recent observational study conducted by scientists at Women's College Hospital in Toronto and the University of Toronto, published in the journal "JAMA Oncology" in August, 2015.

Their conclusions are based on the largest recorded data ever analyzed, based on 18 U.S. registries including 100,000 women followed for 20 years with a diagnosis of ductal carcinoma in situ (DCIS).

It should be reminded that this is not a cancer, contrary to what its denomination might seem to indicate. It is a precancerous/adenomatous lesion that remains inside the mammary canal without invading the surrounding tissues. It is a lesion with a good prognosis, it corresponds to stage 0 of breast cancer. This type of precancerous lesion is diagnosed much more frequently since the widespread use of mammography. Some of these lesions are thought to be precursors of breast cancer. There is a risk for patients of local recurrence into either DCIS or infiltrating ductal carcinoma, which is potentially metastasizing and therefore life-threatening.

However, it is not yet known how to determine which DCIS will progress to infiltrating cancer and which will not. The patient usually is treated by a partial or total mastectomy, depending on the extent, and in any case a total mastectomy upon recurrence, followed by radiation therapy. Until now, this treatment was considered to have a preventive effect on the development of invasive cancer and was therefore beneficial for the patient's survival.

It now would seem that the treatment does not make a difference on survival and women with this condition and even heavily treated (sometimes by bilateral mastectomy) have the same probability of dying from breast cancer compared to women in the general population.

Prevention of recurrence with either radiotherapy or mastectomy did not prevent death from breast cancer.

Therefore, the treatment of precancerous lesions (DCIS) seems excessive in breast pathology. Moreover, in colonic pathology, precancerous lesions are never treated by radiotherapy.

According to Philippe Autier from the International Prevention Research Institute (IPRI), the situation is impossible to solve from a legal and practical point of view, especially since the diagnosis of DCIS can never be 100% certain until the surgical specimen is examined under the microscope. The problem, according to him, is inherent to mammography, especially digital mammography, which is too performant regarding the detection of small calcifications which are the most frequent radiological signs of these forms of precancerous lesions.

He believes that the problem of over-diagnosis, i.e. the detection of in situ or invasive cancers that would not have manifested themselves and would not have threatened patient's life, will not be eliminated as long as screening is based on this method.

This reasoning can be taken one step further: it seems quite pointless that current technology tends to invent increasingly sensitive detection methods that will serve for detecting precancerous lesions, of which many will never develop into cancer...

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.

Impact of screening mammography on breast cancer mortality

https://www.ncbi.nlm.nih.gov/pubmed/26562826

Archie Bleyer1,†,*, Cornelia Baines 2 and Anthony B. Miller 2
Version of Record online: 15 DEC 2015 DOI: 10.1002/ijc.29925

© 2015 UICC
Issue International Journal of Cancer
International Journal of Cancer
Volume 138, Issue 8, pages 2003–2012, 15 April 2016

Archie Bleyer, MD is Chair of the Institutional Review Board for the St. Charles Health System in Central Oregon and author/co-author of over 100_original_reports on clinical research that required CISR approval. He is also a clinical research professor.

Archie Bleyer, Professor of Clinical Research at the Oregon University of Science and Health published together with G.Welch, American cancer researcher in 2012 in the NEJM, an update on the effects of three decades of screening on breast cancer incidence from 1978 to 2008.  The finding of the study was that the small reduction observed in advanced cancers was not proportional to the impressive increase (doubling) in the early stage cancers.

This year Archie Bleyer and Tony Miller, Professor Emeritus at the University of Toronto, who conducted a 25-year follow-up study of women from Canadian trials*, are studying the extent to which reduced breast cancer mortality is attributable to screening mammography. The authors examine the impact of screening mammography along three dimensions:

1) A chronology study, to see if the decline in breast cancer mortality would be correlated with the introduction of screening campaigns.

2) A magnitude study to examine whether the decline in mortality would be proportional to the rate of screening mammography.

3) And then, an analogy study,  by studying the mortality reduction model for other forms of cancer, for which population screening is not conducted.

Regarding the first two axes of study, using data from eight European and North American countries, the authors find no correlation between the penetration of national screening and either the chronology or magnitude of national breast cancer mortality reduction.

(Indeed, since the 1990s, cancer mortality has been decreasing, but the reasons highlighted by other studies (Autier, Jorgensen, Kalager) are essentially therapeutic progress, and perhaps the effects of real prevention campaigns against risk factors are also being seen)

The magnitude of the mortality decline is even greater in the unscreened, younger women than in the screened population, as observed in the United States.

There is no correlation between the extent of screening and the magnitude of the decrease in cancer mortality in recent years.

Finally, the comparative study of 14 other types of cancers shows a similar decline in mortality rates for these cancers, even though these other cancers are not subject to screening campaigns.

*Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial.

BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.g366 (Published 11 February 2014)

Quote this as: BMJ 2014;348:g366 https://www.bmj.com/content/348/bmj.g366

CONCLUSION :

The authors conclude that the degree to which observed reductions in breast cancer mortality is attributable to screening mammography has become increasingly controversial.

A comparison of eight countries in Europe and North America shows no correlation between national screening penetration and either the chronology or magnitude of national breast cancer mortality reduction.

Evidence from the three different approaches and other additional observations do not support the hypothesis that mammography screening is a primary reason for  breast cancer mortality reduction in Europe and North America.

See also: https://www.bmj.com/content/343/bmj.d4411

Pr P. Autier conclusions: The contrast between the timing of breast cancer screening being implemented and the similarity in mortality reduction between the country pairs do not suggest that a large proportion of the mortality reduction can be attributed to mammography screening.

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.

Vegetarianism and cancer

By Cancer Rose

1 December 2020

The fact that eating habits have an influence on the risk of developing cancer, and that the incidence of cancer among vegetarians in particular is lower than among people having a meat diet, has already been the subject of scientific studies [1].

A more recent publication [2] than the above-mentioned one, analyzing 86 cross-sectional studies and 10 prospective cohort studies, reports a significant protective effect of a vegetarian diet on the incidence and mortality of ischemic heart disease (-25%), and on overall cancer incidence (-8%). The vegetarian diet was found to significantly reduce the overall risk (-15%) of developing cancer.

But a post by the physician essayist and novelist, Dr. Luc Perino, whose articles [3] we often relay, testifies to another aspect of the behavior of vegetarians and vegans that could have an effect on the reduced incidence of cancer among this group of people, namely the lower participation in screening.

Non-carcinogenic diet and participation in screening / opinion column by Luc Perino

We publish here, with the kind permission of Dr. Perino, the post that you can read, among many others, on the author's blog [4]:

There is no longer need to conduct studies in order to prove that lower meat consumption reduces the incidence of cardiovascular disease. The subject is no longer under debate since half a century. Decreased meat consumption and physical exercise have contributed to the new gains in life expectancy observed in recent decades. 

We also know that low-meat diets reduce the risk of colon cancer. In recent years, the large number of vegetarians has made it possible to carry out studies of greater statistical value on the effects of such diets on health. The question of cancers has obviously been addressed and it appears that in addition to colon cancer, the vegetarian diet also reduces cancers as unexpected like breast and prostate cancer. Generally speaking, all cancer risks are reduced to a greater or lesser extent.

Confounding factors such as tobacco have obviously been taken into account, and some studies went so far as to consider other confounding factors such as personality traits and other elements of a reasonable vegetarian lifestyle (excluding fanatical vegans). For example, vegetarian women take fewer hormone treatments during menopause and further reduce their risk of breast cancer.

The funny thing, if I dare to phrase it this way, is that vegetarians participate much less in organized cancer screening programs. Some will conclude that they are carriers of unknown cancers that will develop sooner or later. This hasty conclusion, somewhat tainted by pro-screening ideology, is contradicted by lower overall cancer mortality among vegetarians of all ages who are followed for a long time.

This is explained by the fact that many of the cancers detected are either false positives or cancers that would never have had a clinical manifestation before death from another cause.

Vegetarians therefore have fewer clinical cancers, fewer detected cancers and fewer virtual or sub-clinical cancers. The health benefit of this triple protection is even greater than that already observed in the reduction of mortality. Indeed, the anxiety associated with all screening and the biographical stigma associated with a cancer diagnosis aggravates morbidity and mortality. We know that all cancers, whether clinical, screened or virtual, have the same psychological and biographical repercussions.

We will not go so far as to encourage vegetarians in their diagnostic recklessness, as this could shock the academy. Nevertheless, we must congratulate them for their sanitary perspicacity and their serenity in the face of pathological destiny, without forgetting to praise their climatic altruism.

Study on participation in screening

In the bibliography of this post, cited by the author, we find a study published in the BMJ in 2017 on health behaviors according to population groups following specific diets [5].

31,260 participants were studied from four diet groups (18,155 meat eaters, 5,012 fish eaters, 7,179 vegetarians, 914 vegans) in the British EPIC-Oxford cohort [6]. 

Compared to meat eaters, vegetarian and vegan women reported lower participation in breast cancer screening, and vegetarian men were less likely to undergo PSA testing for prostate cancer. 

No difference was observed in women for cervical cancer screening. 

For women in all non-meat eating groups there was also a lower consumption of hormone replacement therapy for menopause compared to meat eaters. 

Less use was observed for any kind of medication in general among participants in all no-meat groups. 

Conclusion

Behavioral differences, rather in the sense of lower participation in breast cancer screening, prostate cancer screening, lower hormone replacement therapy and overall drug use were observed in the non-meat diet groups. Apparently these population groups are thus less exposed to the risk of developing cancers, less exposed to clinical cancers (revealed by symptoms), and to sub-clinical cancers (not symptomatic), whose over-detection unbridled by mass screening feeds over-diagnosis, and all this in a context of less anxiety, less morbidity and less premature mortality among vegetarians, observed even in the long term, probably in relation to a healthier general life behavior, and not only due to vegetarianism alone [7].

References

[1] https://academic.oup.com/ajcn/article/89/5/1620S/4596951?searchresult=1

[2] https://pubmed.ncbi.nlm.nih.gov/26853923/

[3] https://cancer-rose.fr/2017/07/04/les-billets-de-luc-perino/

[4] https://lucperino.com/715/vegetariens-et-cancers.html

[5] https://bmjopen.bmj.com/content/7/12/e018245

[6] The Oxford Component of the European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort of 65,000 men and women living in the UK, many of whom are vegetarians.

[7] https://theconversation.com/les-vegetariens-vivent-ils-plus-longtemps-probablement-mais-pas-parce-quils-sont-vegetariens-72929

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.

Cancer diagnosis: the bone of death or symbolic effectiveness

Annette LEXA, PhD Toxicology (Eurotox)

Expert Regulatory Toxicologist-Environmental Health Risk Assessor

22 February 2016

In today's health care system, a cancer diagnosis can be the most traumatic announcement that a patient will ever experience. And for some people, the announcement will be even more deadly than the cancer itself or its treatment. This is what a cohort study published in 2012 in the New England Journal of Medicine has masterfully demonstrated. The follow-up of this historical cohort of 6 million Swedes between 1991 and 2006, examined the link between cancer diagnosis and the immediate risk of suicide or death from a cardiovascular accident. In the first week after the announcement, the relative risk of committing suicide was 12.6 and the relative risk of dying from a cardiac accident was 5.6 compared to the control group without a cancer diagnosis. This indisputable result is observed equally in men and women.

According to the authors, a negative attitude from the healthcare professional, his or her beliefs around a diagnosis, will cause a deep distress to the patient, especially for cancers with a poor prognosis, leading to death within a week of diagnosis.

The major public health campaigns, the health system and the health professionals themselves, who are part of this dreaded particular colloquium, should be better consider this syndrome in their decision-making process based on the benefit-risk analysis, this potentially fatal psycho-physiological stress induced by the diagnosis itself.

Marcel Mauss and the death bone 

This study, which followed the standards of Evidence Based Medicine, confirms what ethnologists such as Claude Levy-Strauss in 1946 or Marcel Mauss in 1926 had already studied in the 20th century. This fatal syndrome is better known as "bone-pointing syndrome". This ancestral practice has been described among the first peoples of Australia, New Zealand and Polynesia. It consists in condemning a person to die after pointing towards to him a few meters away, a thin bone (often a kangaroo or emu femur of about 45 cm). This ritual is still at use today in Australia where health professionals are trained to face these fearsome situations, where the strength of beliefs prevails to the point of making the victim die from panic fear that disrupts the instinct of conservation, life itself. It is not a death of starvation where the individual would have let himself die of hunger and thirst, no, it is a panic fear that leads to a very rapid death that is not a deliberate choice of the individual or a death due to pre-existing psychological disorders, which the researchers verified in the Swedish study.

Marcel Mauss (1872-1950) wrote the following in 1926: "The Australians consider to be natural only those deaths that we call violent . (...) All the other deaths have a magical or religious origin (...). Mr. Mac Alpine employed a young Kurnai in 1856-57. This young boy was very healthy. One day, he fell ill. He explained that he had done what he shouldn't have done. He had stolen a female opossum before having permission to eat it. The old men had found out about it. He knew that he would not grow any more. He went to bed, practically under the effect of this belief; he never stood up again and died within three weeks. 

(…) Two recent observers, one of whom is a doctor, tell how people die from the death bone among the Wonkanguru: they are very scared. If this bone is found, the bewitched one gets better; if not, he gets worse. European medicine does not inspire confidence. It can do nothing (...) "

Mauss quotes Sir Barry Tuke, a physician who attests to having known "a healthy individual with a Herculean constitution". He died of this "melancholy" in less than three days. Another, "in excellent appearance, and certainly without any lesions of the thoracic viscera, was grieved by life: he said he was going to die and died in 10 days". In most of the cases studied by the doctor, the period was two or three days.

Marcel Mauss reminds us that sociology, like psychology, is only part of biology. Ideas that haunt the social body (death by cancer) have an immense capacity for development and persistence in individual consciousness. It is at the level of biology, of the psychophysiology of the individual that the collective suggestion crystallizes; the consciousness is entirely invaded by ideas and feelings that associate cancer and inevitable death and that are entirely of collective origin. Individuals die "by enchantment". Our human societies are animal societies, highly evolved indeed, but animal societies above all. And man is only a symbolic social mammal for whom language and symbols are powers that sustain his impulse of life and death.

Claude Lévy-Strauss and symbolic effectiveness

Claude Levy Strauss (1908-2009) later formulated the concept of symbolic effectiveness, based on the work of the American physiologist Waler Bradford Cannon (1871-1935). Cannon theorized the famous principle of the fight-or-flight response. In the face of a threat, if fighting or fleeing is no longer possible, physiological stress puts the organism in danger (illness, death). "An individual conscious of being the object of an evil spell is intimately persuaded, by the most solemn traditions of his group, that he is condemned: parents and friends share this certainty. From then on, the community retracts: one moves away from the cursed one, one behaves towards him as if he were not only already dead, but a source of danger for all those around him...".

Of course, there has to be a belief in "magic". This symbolic power implies a macabre ballet of three: the sorcerer, the victim and the group, all must share the same belief, the same trust and the same requirement. The fundamental problem is the relationship of a certain type of individual that we might qualify as easily influenced by certain requirements and beliefs of the group (cancer is an inexorably deadly and horrible disease that threatens and terrorizes us all).

Announcement consultation or "the pink bone".

The passive patient-victim and the active doctor-shaman then engage in this macabre dance orchestrated by the health care system around the panic fear of cancer: the doctor must at all costs fight this modern-day plague that threatens the entire community. His feverishness in making appointments for further tests and treatments reinforces the idea of imminent death. Some patients are convinced that they are already, in a way, banished from the world of the living. Society as a whole is threatened by cancer (how else to explain this collective obsession to "fight against cancer"?) and each new diagnosis is threatened with expulsion from the social body (work, family, insurance, bank...). Her stress is such that some of them can lose control of their lives, all choice. Their metabolic, psychophysiological and even vital functions are in danger. The victim succumbs without having been able to fight or flee: they die of a heart attack if their constitution allows it, otherwise they commit suicide under the effect of the dramatic collapse of their neurotransmitter balance.

The obsession with breast cancer screening, with its lot of over-diagnoses, stems from this hysterized macabre dance, linking women, doctors and the social body: terrified at the idea of being socially banished, how many pre-cancerous or cancerous women have already been victims of this disastrous fate by the collapse of their vital defenses? Nobody knows it and nobody wants to know it, the important thing is to fight cancer at all costs, isn't it? Without going as far as to the death, the announcement of the presence of a cancerous tumor can trigger in some women the collapse of their psycho-neuro-immunological defenses, making even more difficult the medical fight to be carried out during heavy treatments sometimes engaged in excess (surgery, radio- and chemotherapy) and accepted because they seem to be the price to pay to continue to keep its place among the living.

The society tries to exonerate itself and save face by multiplying "empathic" campaigns aiming to give "tips and tricks" on how to "live well with cancer while remaining feminine and keeping one's morale, energy and smile", but some victims, once they have received the ACR4 mark, are not as fortunate as others to have a mind of steel when faced with the symbolic effectiveness of the pink bone.

Bibliography

Cannon W.C., Voodoo death, American anthropologist, 1942, 44(2), 169-181.

Gaudard P.Y.,  Suggestion of the idea of death in Marcel Mauss, acute fatal catatonia, phobia and symbolic modalities, Journal français de psychiatrie, 2010/4 (n°39)

Marcel Mauss, Definition of the collective suggestion of the idea of death. In Sociology and Anthropology, 313-320

Suicide and Cardiovascular Death after a Cancer Diagnosis, Fang Fang et al, N Engl J Med 2012;366:1310-8.

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.

Predictive test for radiotherapy induced reactions: women at high risk

Dr. Annette LEXA (PhD Toxicology)

November 20, 2017

While mainstream media give the impression of discovering a hot scoop and a possible polemic [1] , the French[2] and international biomedical community is now perfectly aware of the limits of breast cancer screening and its burden (limited benefits, imperfect sensitivity and specificity [3], over-diagnosis, "preventive" surgery, morbidity and mortality by radiotherapy) but does not communicate this fact to the general public.

Cancer Rose with FORMINDEP (french non profit organization for independent medical education and information), with several independent general practitioners on social networks (Jean Claude Grange, Claudina Michal-Teitelbaum, JB Blanc, Dominique Dupagne, Jaddo, etc.) and several women (Martine Bronner, Rachel Campergue, etc.) have simply relayed - voluntarily, independently and free of charge - the scientific information available to the first concerned, work which should normally have been done by professionals and which has not been done for 2 main reasons : some have severe cognitive biases, others are very afraid of the "feelings" of women who might lose "confidence" in screening, which must therefore be improved as soon as possible. This probably explains this first Pink October 2017, which is strangely silent.

Regarding the risk associated with radiotherapy, Cancer Rose had already alerted women to the risk [4]. However, it continues to be largely underestimated [2]. Following an e-mail sent to us by an anxious woman on October 4, we looked for an update on the predictive tissue radiosensitivity tests available in France [5]. And what we discovered is not very pleasant, we should say again.

Radiosensitivity is a real public health problem

60% of the 380,000 new cases of cancer in France are treated by radiotherapy. Patients receive sessions of the order of 2 Gy [6], repeated daily. Even with state-of-the-art equipment, the risk of irradiating healthy connective tissue [7] is unavoidable.

 Among patients treated by radiotherapy, 5 to 20% may show adverse reactions such as dermatitis, fibrosis, rectitis (this is called tissue radiosensitivity), secondary radiation-induced cancers [8] (between 5 and 12%) (this is called cancer radio-susceptibility).  At present, no personalized medicine currently takes into account the individual risk of radiosensitivity or radiosusceptibility. Moreover, international radiation protection rules (e.g. Sievert[6] still consider individuals as being all radioresistant for these two concepts. Even nowadays, people are exposed to the same dose of radiation that can lead either to a cure without side effects, a cure with more or less serious to fatal side effects in the case of coronary artery disease, or even death in 100% of exceptional cases of well-characterized rare genetic diseases. All treatment parameters are set without taking into account individual variations. Therefore, a person who will have a 10 times higher risk of developing cancer, will still receive the same dose as a person repairing his DNA lesions well and is unlikely to develop secondary cancer.

Indeed, the biggest problem is the double-strand breakage of the DNA (which we will call DSB, it is the most serious lesion that can be suffered by the DNA because both copies are affected). Normally the repair of DSB is initiated by a cytoplasmic protein called ATM. For about fifteen years, the Radiobiology Group of UMR 1052 INSERM (Lyon) has been working to understand this mechanism and to develop an individual predictive test.

This protein is activated for any oxidative stress producing DSBs and passes into the nucleus to trigger DNA repair. This group of researchers has identified 3 groups of humans:

- Group I = radioresistant, low-risk cancer patients who quickly and correctly repair DSBs, which represent about 75-85% of the population.

- Group II = moderate radiosensitive, and radiosusceptible (high risk of cancer), who repair late and with errors even at low radiation doses. Individuals in Group II would represent 20% of the general population. When these individuals are subjected to radiotherapy sessions, they can more easily trigger radiation-induced cancers, but also dermatitis, rectitis, coronaritis, etc.

- Group III = hyper-radiosensitive individuals who do not repair the DSB and are highly radiosusceptible, these present rare genetic syndromes diagnosed early in life (ataxia telangiectasia) and represent 1 person/100,000 but 0.5 to 5% of individuals worldwide would be carriers of a mutation of the ATM gene.

This classification also exists for tumor cells, independently of the group of healthy tissues (e.g., a group II patient may show group I, II or III tumors).

Finally, there is the problem of the repetition of low doses that can overwhelm the restorative capacity of the irradiated cells. This risk must be taken into account for young patients at high family risk. It is also known today that people with the BRCA1 or BRCA2 mutation have a risk associated with a certain radiosusceptibility, as well as people carrying mutations on p53 or ATM.

In addition to the risk associated with radiotherapy, the risk associated with radiodiagnosis should not be overlooked.  It accounts for the majority of medical exposures, usually to healthy individuals. If the exposure dose is 100 to 1000 times lower than in radiotherapy, the average exposure is constantly increasing : it is justified to question the safety of low doses of irradiation in group II patients, and in particular in young patients carrying the mutation ATM (1% incidence), or BRCA1 (1/1000 incidence) and BRCA2 (1/2000), the latter mutations presenting for the carrier an excess risk of breast cancer by a factor of 5 to 10 (this represents nearly 1% of the general population which has, for women, a risk of breast cancer 5 to 10 times higher than normal). Mammography generates 2 x 2 mGy images, spaced 3 minutes apart. Repeated doses induce CDBs and may induce additional DSBs during repair, thus increasing the effect of low doses. Studies have shown a risk of radiation-induced breast cancer for cumulative doses of 100 mGy. This is one of the reasons why mammograms should not be cumulated too much before the age of 50 and especially not before the age of 30 for women in group II.

Radiosensitivity tests: ATM transit test and apoptosis test 

In order to be truly predictive, a test must meet 3 criteria:

- It must be founded on a solid scientific basis

- it must have been tested on a large number of individuals of different radiosensitivity

- it must show the highest possible statistical power, independent of the dose, the nature of the tissue response and the location of the tumor.

Experience has shown that the more rapid the test, the less powerful it is.

Generally based on non-irradiated cells, proteomic and genomic approaches are currently not convincing and currently no genetic marker or gene expression can claim to predict radiosensitivity.

The ATM transit test

However, a simple test exists today to analyze the activity of the ATM protein in the nucleus during a 2 Gy irradiation of skin fibroblasts taken from the person. This test was developed by the radiobiology group of UMR1052 INSERM (French National Institute of Health and Medical Research) in Lyon. The test is based on the principle that the slower the transit of the ATM protein in the nucleus, the more radiosensitive the patient is. This test can distinguish 5 clinical grades of severity of tissue reactions (equivalent to degrees of burn), its sensitivity is 100% and its specificity 92%.

The development of the ATM test was carried out as part of a larger research project called the COPERNIC project [9]. Two tests will be marketed at the beginning of 2018 by NEOLYS DIAGNOSTICS[10] in several forms: a rapid test[11] (performed in an anti-cancer center, results in 4 to 5 hours) called "first sorting" from a rapid skin or blood sample for a few hundred euros, and a complete test* from a cutaneous sampling (3 weeks). The radiobiology group of the UMR1052 Inserm and the company NEOLYS DIAGNOSTICS collaborate, within a framework set by the Inserm deontology commission, to better define the regulations and ethics regarding radiosensitivity issues in order to give a clear legal framework to the use of these tests, which are always prescribed by doctors.

ATM transit theory also finds applications for toxicity related to non-radiative agents such as metals or pesticides: tests are being developed in this direction, which requires absolute rigor in the management of information and the implementation of alternatives when they would prove to be positive.

*In fact the price of the characterization test has not yet been finalized. It should be around 2,000€ (instead of 1,500€ as indicated) for the 3 weeks required for this test in a specialized medical analysis laboratory (excluding the anti-cancer center). Thanks to Mr. Gilles Devillers - pharmacist - president of Neolys Diagnostics, for the clarifications made.

The apoptosis test

There is another test model based on the apoptosis[12] of lymphocytes circulating in the blood, irradiated at 8 Gy. But this model is only valid for lymphocytes (which have been shown not to be the best candidates to represent breast connective tissue) and, moreover, the dose is higher (remember that a radiotherapy session exposes to a dose of 2 Gy). Originally, this test is only valid for delayed tissue reactions (such as those observed in some prostate cancers). It is based on the premise that more apoptosis means more radioresistance, which is contrary to the consensus observation that the more radio-induced death is observed, the more radiosensitive the cells are.

In addition, this test is based on the premise that lymphocyte death can predict the death of other types of tissue, such as conjunctive tissue, which rarely apoptoses.

The apoptosis criterion is all the more problematic as the test uses a high dose of 8 Gy (there is systematically a rapid apoptosis in 24 to 48 hours at this high dose).

At 2 Gy, there is less apoptosis and moreover it is observed at this dose that the more extensive the apoptosis, the more radiosensitive the patients are (Baijer et al, 2016 ). The figures put forward suggest that the test based on lymphocyte apoptosis shows lower statistical performance than the ATM test. Finally, the recruitment of patients for the development of the test can be problematic: the prospective aspect [13] of the trials favors rather radioresistant subjects and the performance of the test to detect radiosensitive patients is therefore based on a few dozen patients, which can introduce an undiscussed bias.

 This test is currently being developed by the company NOVAGRAY [14]. On its website, the company proposes to adapt the dose and the sequence of the sessions "to the woman patient's profile" when the patient has agreed to pay 1500 euros for this test. Evoking "a woman patient" leaves one wondering: since the test was initially developed for prostate cancer, the breast not being explicitly mentioned, is the woman more willing to buy a test than a man patient? This is all the more surprising since the site states that tests for prostate and lung cancer are in development. This suggests that the test currently available at NOVAGRAY is not specific for breast cancer.

CONCLUSION

There is little clear and accessible information on this type of personalized medicine for women facing breast cancer screening and treatment. And yet, it is vital for them. Patients already weakened by the announcement of the disease and the care pathway to be undertaken cannot alone assume the choice of a radiosensitivity test. Does the doctor prescribing this non-reimbursed test provide them with balanced and up-to-date information?

How can they discern between apoptosis and ATM testing for a comparable price? Should cheaper first-sort tests be favored? Moreover, while radiosusceptibility tests could be developed through the ATM transit theory, apoptosis (and therefore cell death) tests do not meet patients' expectations regarding mammographic exposure.

We are facing an extremely serious inequality of access to information and innovation, while lives are at risk. Despite the very complex mechanisms of individual response to radiation, there is now an urgent need for the authorities to take into account and better frame all issues related to individual radiosensitivity and radiosusceptibility.

BIBLIOGRAPHIE :

- Influence of Nucleoshuttling of the ATM Protein in the Healthy Tissues Response to Radiation Therapy: Toward a Molecular Classification of Human Radiosensitivity , The COPERNIC project investigators,
 Int J Radiation Oncol Biol Phys, Vol. 94, No. 3, pp. 450- 460, 2016

- The Henri Mondor Procedure of Morbidity and Mortality Review Meetings: Prospective Registration of Clinical, Dosimetric, and Individual Radiosensitivity Data of Patients With Severe Radiation Toxicity , Yazid Belkacemi et col. , Int J Radiation Oncol Biol Phys, Vol. 96, No. 3, pp. 629-636, 2016

- TNFSF10/TRAIL regulates human T4 effector memory lymphocyte radiosensitivity and predicts radiation-induced acute and subacute dermatitis, Baijer et col., Oncotarget. 2016 Apr 19;7(16):21416-27

- Radiation-induced CD8 T-lymphocyte Apoptosis as a Predictor of Breast Fibrosis After Radiotherapy: Results of the Prospective Multicenter French Trial, David Azria et col. , EBioMedicine,  December 2015 Volume 2, Issue 12, Pages 1965–1973

 - Low radiation doses: towards a new reading of risk assessment? Anne-Fleur Perez, Clément Devic, Catherine Colin, Nicolas Foray , Bull Cancer 2015

- Individual radio sensitivity: an old notion and its future , Conclusions of the December 16, 2013 seminar organized by the ASN , 2014

- Radiosensitivity Evidence of an individual factor, Nicolas Foray, Catherine Colin and Michel Bourguignon, Medicine/Science 2013; 29: 397-403

- 100 years of individual Radiosensitivity: How We Have Forgotten the Evidence, Nicolas Foray, PhDCatherine Colin, MD, PhD Michel Bourguignon, Radiology: Volume 264: Number 3—September 2012

- DNA double-strand breaks induced by mammographic screening procedures in human mammary epithelial cells , Catherine Colin et col. , Int J Radiat Biol. 2011 Nov;87(11):1103-12.

 [1]Breast cancer: the relevance of screening in question, Catherine Ducruet, Les Echos.fr, 07/10/17 - https://www.lesechos.fr/industrie-services/pharmacie-sante/030668058097-cancer-du-sein-la-pertinence-du-depistage-en-question-2120226.php#FFEP5i8Gtd07a53G.99

[2] Delaloge S, et al. Breast cancer screening: on the way to the future. Bull Cancer (2016), http://dx.doi.org/ 10.1016/j.bulcan.2016.06.005

[3] The sensitivity of a test is its ability to detect as many " ill people " as possible (false negatives are avoided). Specificity is its capacity to detect only ill people (avoid false positives).

 [4] Mammograms and radiosensitivity, Annette LEXA , https://www.cancer-rose.fr/mammographies-et-radiosensiblite

[5]  "Being very anxious about the effects of radiotherapy, I discovered a company (Novagray) that markets a radiosensitivity test. In April 2017 this test was not reimbursed and costs 1500 euros. I finally did not accept this test for financial reasons but also because in case of non-radiosensitivity the number of sessions is decreased and the dose increased, which did not seem reassuring to me. Do you know this test and can you give me your opinion? My radiotherapy sessions are over but I refuse the control mammogram, considering that there is no consideration of all the accumulated radiation. »

[6]  The sievert (Sv) is an international unit used to give an assessment of the biological impact of radiation on humans. The Gray (Gy) is the absolute dose of radiation received/Sievert. A dose of 2 Gy is about 1000 times the dose received for a mammogram image.

[7] Connective tissue is the supporting tissue (collagen fiber, fat tissue, dermis, etc.) but also blood cells (macrophages, leukocytes, etc.). These are tissues that have the same embryonic origin. However, not all scientific authorities consider blood or lymph as connective tissue. The breast is an organ that contains mainly connective tissue.

[8]  For a 50-year-old woman with small breast cancer, the absolute benefit expected from radiotherapy is a reduction in breast cancer mortality of about 2-5%. For non-smokers, the absolute risk of developing lung cancer or cardiotoxic risk 10 years after breast cancer radiation therapy appears to be less than 1%. For smokers, the absolute risk is 4%.

Estimation des risques de la radiothérapie du cancer du sein : Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials, Taylor C. et al, J Clin Oncol. 2017 20 mai ; 35(15):1641-1649).

This lack of benefit on overall mortality is also noted in a report in French of 2015, Evaluation of intraoperative radiotherapy in breast cancer, October 2015, Note de cadrage, HAS, October 2015. http://www.has-sante.fr/portail/upload/docs/application/pdf/2015-10/cadrage_rtpo.pdf)

[9] The COPERNIC project: http://www.radiobiologie.fr/index.php?tg=articles&idx=More&topics=6&article=37

[10] SAS NEOLYS (http://www.neolysdiagnostics.com/fr/ ) was founded by the founders Gilles Devillers, Nicolas Foray, Julien Gillet-Daubin. It is based on the 15 years of work of the Radiobiology Group of UMR 1052 INSERM.

[11] This rapid test was recently accepted in Int J radiat Biol Oncol Phys

[12] Apoptosis is one of the forms of cell death by self-destruction (a kind of cell suicide), genetically programmed.

 [13] A prospective study consists of comparing the occurrence of a pathology in groups defined according to their exposure to a factor presumed to be responsible for the pathology.

[14] SAS NOVAGRAY is directed by Clémence Franc who co-founded NOVAGRAY with Prof. David Azria in 2015.  Pr AZRIA is head of the Oncologic Radiotherapy Department at the Cancer Institute of Montpellier (ICM) and radiobiology project leader in the team "Immunociblage et radiobiologie en oncologie" directed by André Pélerin at the head of the INSERM U1194 unit at the Cancer Research Institute of Montpellier (IRCM).

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 excess of mortality due to treatment outweighs the benefit of breast cancer screening: synthesis of several studies

 8 August 2019

Several international researchers complain about the fact that by making estimates of specific breast cancer mortality, the deaths resulting from heavy treatment that women undergo after cancer detection are largely underestimated. Assessing overall mortality would also allow the inclusion of deaths due to treatment.

In a synthesis, Gotsche, a former Cochrane Collaboration Investigator, an independent collective of Nordic researchers, writes :

I believe that if screening had been a drug, it would have been withdrawn from the market long ago. Many drugs are withdrawn although they benefit many patients, when serious harms are reported in rather few patients. The situation with mammography screening is the opposite: Very few, if any, will benefit, whereas many will be harmed. I therefore believe it is appropriate that a nationally appointed body in Switzerland has now recommended that mammography screening should be stopped because it is harmful.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4582264/

1° Michael Baum's study :

https://www.bmj.com/content/346/bmj.f385

Harms from breast cancer screening outweigh benefits if death caused by treatment is included

Over the past 30 years, the percentage of patients undergoing chemotherapy has increased from 20% to about 80% [1]. It is obvious that chemotherapy will expose the patient to effects on her survival, her comfort of life, expose her to other morbid effects [2] [3].

Anti-hormonal treatments (anti-aromatases or Tamoxifen) can cause thromboembolic complications and myocardial infarction. A risk of secondary endometrial cancer with Tamoxifen has been noted. [4] [5] Women may experience earlier signs of menopause, arthralgia, neuropathies and cognitive dysfunction, weight gain....

Radiotherapy can cause heart and lung complications. The risk of radiogenic coronaritis increases by 7.4% per gray received by the heart and is the cause of sometimes major cardiac problems and poor prognosis. [6] [7]

But also more serious diseases such as haemopathies [8] and radiation-induced lung or oesophageal cancers. [9]

For all these reasons, Michael Baum, Professor Emeritus of Surgery, a British oncologist specialized in the treatment of breast cancer, concludes: « harms from breast cancer screening outweigh benefits if death caused by treatment is included »

2° A 1989 publication

https://www.bmj.com/content/298/6688/1611

Authors' CONCLUSIONS - Adjuvant radiotherapy after simple mastectomy for early breast cancer results in a slight excess of late mortality due to other cancers and heart disease. The risk must be weighed against the higher risk of local recurrence in the absence of immediate postoperative radiotherapy. The balance must be assessed for each patient ....

3° A disturbing Brazilian study :

https://bmjopen.bmj.com/content/7/8/e01639

We have analyzed this study here :  https://cancer-rose.fr/2017/11/12/surmortalite-imputable-au-depistage-une-etude-bresilienne-troublante/

The direct association between higher breast cancer mortality and the proportion of women who use the private health sector (and use screening more often) is in line with studies on the subject published in Brazil. This counter-intuitive conclusion of increased access to health care leading to increased mortality can be explained by "over-diagnosis", but the authors also point out that wealthier women are more exposed to potential carcinogens.

According to the authors, mammography screening did not have a positive effect: rather, it was associated with an increase in breast cancer mortality.

Treatment of breast cancer has many side effects that can result from surgical complications, radiation therapy, chemotherapy and anti-estrogen therapy. The authors note that the absence of a decrease in all-cause mortality between screened and unscreened populations has been attributed to the additional risks of treatment, which are more common in screened women. The increased risks of cardiovascular disease due to cardiac toxicity from anthracycline and trastuzumab treatment and radiation therapy are well documented, and the authors also cite radiation-induced cancer due to radiation from mammography and radiation therapy.

4° Danish study of Jorgensen

https://www.ncbi.nlm.nih.gov/pubmed/20332505

https://www.bmj.com/content/340/bmj.c1241

Jorgensen k. J. Breast cancer mortality in organised mammography screening in Denmark: comparative study. BMJ. 2010;340:c1241.

The study by Karsten Jorgensen (of the Nordic Cochrane Centre) identified all cases of breast cancer deaths in Denmark from 1971 to 2006 by year, region and five-year age groups (correlated with the total female population). Breast cancers occurring in women excluded from screening (women aged 35-54 and 75 and over) were included. Mortality was observed during the ten years where screening may have had an effect.

The result is surprising because the reduction in mortality appears to be greater in unscreened areas.

Breast cancer mortality in women aged 55-74 was reduced:

- by 1% in areas where screening was available,

- by 2% in areas where it did not exist,

- of 5% in women aged 35-54 years where screening was available,

- by 6% in the same age group in areas where it did not exist.

- No change in mortality was observed in women over 75 years of age.

The reduction in mortality recorded in Denmark is therefore not related to screening, and is even more pronounced in areas where screening is not practiced.

(Indeed, in many countries where screening has been introduced, there has been some reduction in mortality since the 1990s, i.e. before the introduction of screening programs and national campaigns. Therapeutic advances are one explanation for this state of affairs, perhaps also the real prevention campaigns (move more, eat less...), the elimination of hormonal substitutes treatments).

5° A meta-analysis: Positive and negative effects on long-term survival of radiotherapy for early breast cancer: an overview of randomized trials

Published May 20, 2000 DOI: https://doi.org/10.1016/S0140-6736(00)02263-7

(by the Early Breast Cancer Trialists Collaborative Group)

Background

The long-term effects of radiation therapy on mortality from breast cancer and other causes remain uncertain.

The methods

This is a meta-analysis of the 10- and 20-year outcomes of 40 "unconfounded" randomized trials* of radiotherapy for early breast cancer. It is a review of individual patient data on recurrence and cause specific mortality in 20,000 women, half of whom were node-positive.

 The areas of radiotherapy generally included not only the chest wall but also the axillary, superclavicular and internal mammary lymph nodes.

* "Unconfounded randomised trials of radiotherapy": Only trials in which comparisons are "unfounded" are included. By definition, in unconfirmed clinical trials, a group differs from the others only in the treatment of interest.

Results

A reduction of about two-thirds in the local recurrence rate was observed in all trials, largely independent of patient type or type of radiation therapy. Therefore, to assess the effects on breast cancer mortality, the results of all trials were combined.

Breast cancer mortality was reduced but mortality from other causes, particularly cardiovascular, was increased. There was little effect on early deaths, but analyses of later deaths indicate that, on average after the second year, radiotherapy reduced annual breast cancer mortality rates by 13.2% but increased those from other causes by 21.2%. Nodal status, age and decade of follow-up strongly influenced the ratio of breast cancer mortality to other mortality.

Interpretation

Radiotherapy regimen capable of producing a two-thirds reduction in the local recurrence observed in these trials, but without long-term hazard, are likely to result in an absolute increase in survival at 20 years of about 2 to 4% (except for women at particularly low risk of local recurrence).

The average risk observed in these trials, however, would reduce this 20-year survival benefit in young women and would reverse the benefit in older women.

Bibliography

[1]  Spielman, Khalil, Kinetics of tumor proliferation and efficacy of adjuvant chemotherapy. Study of mitotic activity. In: Breast cancer. Proceedings of the postgraduate French-language course in oncology. pp. 455-46

http://eknygos.lsmuni.lt/springer/65/455-463.pdf

[2] Morgan g, WarD r, Barton m. The contribution of cytotoxic chemotherapy to 5-year survival in adult malignancies. Clinical Oncology. 2004 Dec;16(8):549- 60. Review.

https://www.ncbi.nlm.nih.gov/pubmed/15630849

[3]Cancer Drugs Approved on the Basis of a Surrogate End Point and Subsequent Overall SurvivalAn Analysis of 5 Years of US Food and Drug Administration Approvals

Chul Kim, MD, MPH; Vinay Prasad, MD, MPH JAMA Internal Medicine. 2015 Dec;175(12):1992-4.

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2463590

[4] Matthews A  , Stanway S  Long term adjuvant endocrine therapy and risk of cardiovascular disease in female breast cancer survivors: systematic review. BMJ. 2018 Oct 8;363:k3845.

https://www.ncbi.nlm.nih.gov/pubmed/30297439

[5] Fleming CA  , Heneghan HM  et al. Meta-analysis of the cumulative risk of endometrial malignancy and systematic review of endometrial surveillance in extended tamoxifen therapy. British Journal of Surgery. 2018 Aug;105(9):1098-1106.

https://www.ncbi.nlm.nih.gov/pubmed/29974455

[6] Junod B. Lethal side effects and radiotherapy induced cancers of breast cancer overdiagnosed in France. In Preventing Overdiagnosis Conferences. Oxford, 17 Septembre 2014. [en ligne]. http://formindep.fr/effets-indesirables-mortels-et-cancers-induits-par- radiotherapie-des-cancers-du-sein-surdiagnostiques-en-france/

[7]Sarah C. Darby, Ph.D., Marianne Ewertz et al. Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer. The New England Journal of Medicine. 2013;368:987-998.

https://www.nejm.org/doi/full/10.1056/NEJMoa1209825

[8] Martin MG  , JS Welch et al. Therapy related acute myeloid leukemia in breast cancer survivors, a population-based study. Breast Cancer Research and Treatment. 2009 Dec;118(3):593-8.

https://www.ncbi.nlm.nih.gov/pubmed/19322652

[9] Bois ME , Vogel V  et al. Second malignant neoplasms: assessment and strategies for risk reduction. Journal of Clinical Oncology. 2012 Oct 20;30(30):3734-45.

https://www.ncbi.nlm.nih.gov/pubmed/23008293

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.

Analysis of Harding american study, 2015

6 July 2015

Breast Cancer Screening, Incidence, and Mortality Across US Counties

Authors : Harding C, Pompei F., Burmistrov D., et al.
JAMA Intern Med. Published online July 06, 2015. doi:10.1001/jamainternmed.2015.3043

Objective

The objective of this study is to try to measure the benefits and harms of breast cancer screening during the year 2000 with a 10-year follow-up, as is carried out in the USA (women over 40 years of age), by comparing data from different counties regarding screening intensity, breast cancer diagnoses, breast cancer mortality, mastectomies. It was carried out on 16 million women and  53207 patients diagnosed with breast cancer.

Results

In counties where screening is more intensive, it is found:

    - an increase in the number of breast cancer diagnoses (+16% for a 10% increase in participation in screening), mainly by tumours smaller than 2 cm.

    - no reduction in breast cancer mortality

    - no reduction in the number of advanced breast cancers

    - no reduction in mastectomies.

(Click to enlarge)

These data are difficult to link with effective mammography screening, where the increase in small breast cancers must be accompanied by a decrease in advanced cancers and breast cancer mortality.

The most likely explanation is that the numerous small cancers detected by systematic mammography are essentially over-diagnoses, i.e. tumors that are not or are very slowly progressive, or spontaneously regressive, whose diagnosis is useless and harmful, whereas screening would not (or rarely) allow a better prognosis for progressive cancers.

Breast cancer mortality in organised mammography screening in Denmark: comparative study » BMJ 2010;340:c1241 http://www.bmj.com/content/340/bmj.c1241

This is a study whose level of evidence is limited by its nature (individual data are not known), but supported by its large size (16 million women), as well as by the additional analyses carried out by the authors.

The trials on which the organized screening of breast cancer by mammography is based are old, and their conclusions (fragile, moreover, because of certain biases and inconsistencies that have since been revealed [1]) cannot be applied to the current situation.

Conclusion

In conclusion, the study confirms the lack of effectiveness of breast cancer screening as found in other studies, including in Europe. [2], [3], [4],[5],[6],[7]

Références

[1] Gøtzsche PC, Jørgensen KJ « Screening for breast cancer with mammography (Review) » The Cochrane Library 2013, https://www.ncbi.nlm.nih.gov/pubmed/23737396


[2] Autier P., Boniol M., Gavin A., Vatten L. J. « Breast cancer mortality in neighbouring European countries with different levels of screening but similar access to treatment: trend analysis of WHO mortality database » BMJ 2011;343:d4411 http://www.bmj.com/content/343/bmj.d4411


[3] Autier P., Boniol M., Middleton R., et al. « Advanced breast cancer incidence following poupulation-based mammographic screening » Annals of Oncology 22 : 1726-1735, 2011 http://annonc.oxfordjournals.org/content/22/8/1726.long


[4] Jørgensen K. J., Zahl P.-H., Gøtzsche P. C. «Breast cancer mortality in organised mammography screening in Denmark: comparative study » BMJ 2010;340:c1241 http://www.bmj.com/content/340/bmj.c1241

[5] Jørgensen K. J., Gøtzsche P. C. « Overdiagnosis in publicly organised mammography screening programmes: systematic review of incidence trends » BMJ 2009;339:b2587 http://www.bmj.com/content/339/bmj.b2587


[6] Junod B., Zahl P.-H., Kaplan R. M., et al. « An investigation of the apparent breast cancer epidemic in France: screening and incidence trends in birth cohorts » BMC Cancer 2011, 11:401 doi:10.1186/1471-2407-11-401, adaptation en français sur http://www.formindep.org/Investigation-de-l-epidemie,487.html


[7] Zahl P.-H., Moehlen J., Welch H.G. « The Natural History of Investive Breast Cancers Detected by Sreening Mammography » Arch Inten Med Vol 168 (n°21) Nov 24, 2008 http://archinte.jamanetwork.com/article.aspx?articleid=773446

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.

Frequency of incidental breast cancer and precancerous lesions in autopsy studies: a systematic review and meta-analysis

Frequency of incidental breast cancer and precancerous lesions in autopsy studies: a systematic review and meta-analysis.

https://bmccancer.biomedcentral.com/articles/10.1186/s12885-017-3808-1

December 14, 2017

Yet another study, other than that of Prof. Autier, recently published in the BMJ* (see at the bottom of the article) reinforces the fear that among the women treated after detection of a cancerous lesion through screening, and therefore in absence of symptoms, a certain number (one out of two in the Autier study from the Netherlands) would never have suffered from it during their lifetime; the removal of a breast, unnecessary radiotherapy or tiring chemotherapy could have been avoided for these women.

Authors :

Elizabeth T. Thomas1 , Chris Del Mar 2 , Paul Glasziou 2 , Gordon Wright 1 , Alexandra Barratt 3 and Katy J. L. Bell 2,3

1 Faculty of Health Sciences and Medicine, Bond University, Robina, QLD 4229, Australia.

2 Centre for Research in Evidence-based Practice, Faculty of Health Sciences and Medicine, Bond University, Robina, QLD 4229, Australia.

3 Sydney School of Public Health, Sydney Medical School, Edward Ford Building (A27), University of Sydney, Fisher Road, Sydney, NSW 2006, Australia

Background

Autopsy studies have demonstrated the frequency of occult cancers in the population, but the evaluations performed by these primary studies involved a small number of deceased patients each time.

Results

The authors included 13 studies from 10 different countries, over 6 decades (from 1948 to 2010), comprising 2363 autopsies with 99 cases of so-called "incidentalomas" (cancers of incidental finding), or precancerous lesions.

When the histological examination was more comprehensive (on more than 20 histological sections), there were more incidentalomas detected, mostly in situ cancers and atypical hyperplasias, but few invasive cancers.

This means that the more histological research is carried out on deceased persons, the more latent cancers are found, with an average frequency of this "accidental" cancer of around 19.5% (0.85% invasive cancer + 8.9% in situ cancer + 9.8% atypical hyperplasia).

Therefore, the more we seek and the more we find, which raises questions about the development of more and more efficient investigative techniques that are going to discover more and more of these lesions abusively. The consequences of the resulting over-treatments are to be considered even more seriously in older women because of the increased susceptibility to adverse effects of treatments in this population.

Conclusion

Systematic review in ten countries over more than six decades has found that incidental discovery of occult, in situ cancers or precancerous lesions is very common in women, in whom breast disease was not known during their lifetime.

It appears that cancerous or pre-cancerous lesions are discovered incidentally in 2 out of 10 women during these autopsies. The authors estimate that 40% of invasive cancers detected by systematic mammography and 24% of all invasive cancers would be over-diagnosed.

This high frequency of undetected cancers, in situ and atypical hyperplasias in these autopsy studies, suggests that screening programs should be more cautious in promoting detection methods with increased sensitivity, thus increasing these unnecessary diagnoses.

*https://www.bmj.com/content/359/bmj.j5224

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.

Perception and reality

3 jan. 2017

How women perceive the data from screening, influenced by optimistic slogans and presentations, versus reality:

When the authors of the report of the Swiss Medical Board (a Swiss medical commission independent from government authorities) evaluated the relevance of the mammographic screening program for breast cancer (see article), (PDF Article) they looked at one data that had been studied in several countries (4), namely how women perceive the benefits of screening according to what has been communicated about it and the information they have received, and that have made their beliefs on the subject.
The authors have presented a comparative table, with data gathered from the perception survey of American women in Part A, and real, objective data from the most probable scenarios, observed from the most convincing and among the most reliable studies in Part B (1-3)
The authors were astonished by the significant discrepancy between women's beliefs about the benefits of screening and reality.


The projected number of women in their fifties who would survive, develop breast cancer and die from other causes while doing regularly screening over 10 years, was compared to the expected number of women who would survive, develop breast cancer or die from other causes, and not doing screening.

71.5% of these interviewed American women estimated that screening mammography reduced by half the risk of dying from breast cancer, and 72.1% believed that at least 80 deaths would be prevented for every 1,000 women invited for screening.
The presentation of mortality risk reduction as a percentage embellishes the data.
A 20% reduction in mortality (a figure found on public institution websites, women committees websites and in the information brochures distributed to women) does not mean that 20 out of every 100 women will die of breast cancer, but that only one less woman will die of it in the best case (and without considering the other, more numerous women screened, who will at the same time suffer from overdiagnosis and false alarms).
The relative risk reduction of 20% corresponds to a comparison between the screened and unscreened groups. If, for example, 5 out of 1000 unscreened women die and 4 out of 1000 screened women die of breast cancer, the relative risk reduction resulting from the comparison of these two groups corresponds to this 20% ((5-4)/5=0.2 ), but in absolute terms it is only one woman who is saved. The data that the authors have collected for the Swiss population show also these optimistic expectations in a similar way.

The authors legitimately ask the question, how can women make an informed decision if the benefits of the screening program are overestimated?
We asked ourselves the same question…and tried to answer it (see the brochure on the home page).

REFERENCES

1-Gotzsche PC, Jorgensen KJ. Screening for breast cancer with mammography. Cochrane Database Syst Rev 2013;6:CD001877-CD001877
Medline

2-Independent UK Panel on Breast Cancer ScreeningThe benefits and harms of breast cancer screening: an independent review. Lancet 2012;380:1778-1786
Medline

3-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-g366
Medline

4-Domenighetti G, D'Avanzo B, Egger M, et al. Women's perception of the benefits of mammography screening: population-based survey in four countries. Int J Epidemiol2003;32:816-821
Medline

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.

Exit mobile version