Category: Questions – Short Answers

Cancer does not always develop as we imagine, in a linear and inevitable way from one cell toward generalization and then the death.
The model that has been taught for a long time was that of a cell which becomes out of control, multiplies in an uncontrolled way, becomes a tumor in an organ, spreads in a local-regional manner, and then generally leads fatally to the death of the organism if no intervention is made.

HOW DOES A BREAST CANCER DEVELOP?

Modern scientific evidence, epidemiological studies and autopsy studies enable us to design other models for the development of breast cancer. (click on pictures)

We have now learned that breast cancer does not develop in a linear manner, but that there are a multitude of possibilities, with slow, even nonprogressive cancers, which, if they are unknown, will not impact a person's life or health; some may even regress, while others may evolve quite fast, and are intrinsically immediately aggressive, due to their molecular characteristics, they are the ones that lead to a true cancer-disease.

The diagrams below explain why screening has failed, with several types of cancer developments.

• Rapidly developing, intrinsically aggressive cancer has a high velocity and a short residence time in the organ, it will be missed by screening. Metastases are often present, even if not yet visible, in lymph nodes or distant organs. It is often big at the time of diagnosis, because it is fast, being found big does not mean late diagnosis.
• Very slow, nonprogressive or regressive cancer, which would not have impacted the patient's life, has a very long residence time in the organ and will therefore rather be detected by repeated screening. Its diagnosis is useless for the patient, yet it will be treated with the same aggressiveness. It is small at the time of diagnosis because it is slow; small does not necessarily mean "early".
• The cancer which develops progressively will one day be symptomatic and detected by the patient by the appearance of a clinical sign, this cancer can be treated in time, because the evolution towards the generalization stage takes a very long time (10, 20 to 30 years).

Having a cancerous tumor does not automatically lead to a cancer-disease. However, this is what women are made to believe by telling them that they have been cured thanks to the detection of a tumor that would never have killed them. On the other hand, the rate of serious cancers has not decreased since the screening in place.

There is a difference between a screening mammogram and a diagnostic mammogram.

• A screening mammogram is the routine mammogram that you are asked to have every two years, even though there are no symptoms, upon screening invitation letter
• A diagnostic mammogram is one that is prompted by the appearance of a sign or symptom in the breast. This symptom requires an exploration by mammography, among other imaging techniques, in order to identify and diagnose the problem in the breast.

What are the major signs that should lead you to consult?

• Modification of the roundness, of the general shape of the breast (irregularities, distortions).
• Retraction of the nipple
• Recent lump or swelling, especially if there is little mobility when palpated.
• Flat, i.e. the flatter area of the breast, which disrupt the roundness of the breast.
• Bloody discharge
• Unexplained redness
• Lump in the armpit, persistent or increasing in volume
• "Orange peel" with the appearance in the affected area of "pads", small blisters perceptible between two fingers.
• Wound on the skin, due to ulcerative cancer
• Swelling and firmness of the entire breast
• Deeply palpable mass, occurring without visible external deformation
  Beware, not all of these signs are typical of cancer; they can also be indicative of benign breast disease! Nevertheless, they should motivate you to consult a doctor.

Screening mammography is not a prevention method.

-Preventing a disease means doing everything possible to ensure that it does not occur. For example, avoiding smoking is a good preventive attitude towards lung cancer.

-Screening is searching for a disease in a person who has no symptoms, and who does not complain about anything at all. Repeating mammograms can in no way prevent breast cancer. The mammographic image restitutes what is already present in the organ.

How does a mammography screening take place in France ?

In practice, the woman notified to attend makes an appointment at the radiology office of her choice. She will have a mammography exam followed by an ultrasound examination depending on necessity (dense breasts or radiological abnormality to be clarified). These images will be interpreted by the radiologist, who is the "first reader" of the examination. He will make a report and propose a classification of the examination (see below). This file (images and report of the first reader) is sent to the departmental structure in charge of managing the screening depending on the patient residence. The images will be reviewed there by another radiologist, the "second reader" , coming from another radiology office or medical imaging structure, and who does not know the woman patient. He will establish his verdict without having seen or questioned her, only on the available images. He will 'report' his verdict in the form of a classification, either in concordance with the first radiologist reader or, on the contrary, in discordance, which will imply a call back of the woman patient for further exploration.
Mammography classification is a radiological classification, depending on the greater or lesser degree of certainty that the imagery pleads in favour of a cancerous lesion. It is by no means a prognostic classification. The ACR (American College of Radiology) classification was developed in 1990. There are 5 stages.

ACR 1: normal, the breast is "nothing to report".
ACR 2: images which are just benign abnormalities, such as small axillary ganglions, micro cysts, benign calcifications, images which are not always known what they are but which have remained unchanged for ages, amorphous fibro-adenomas, or cysts which are already well known.
ACR 3: an image which is not worrying but whose outcome are wished to be checked, which has not been known before, or which was been known but has changed slightly compared to previous evaluations. The proposed conduct is a single monitoring at 4 or 6 months, depending on whether masses or calcifications are involved, and then eventually at one year.
ACR 4 means that there is a high probability of cancer, and in any case a suspicious anomaly, to be further investigated. 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.
ACR 5: the anomaly is very strongly suspected of malignancy and the semiological criteria are quite representative and typical of malignancy.
ACR 0 designates an incomplete examination to which other imaging examinations must be associated.

For more explanations and details read here: https://cancer-rose.fr/en/2020/12/30/arc-classification/
Below is a diagram that illustrates the possible situations during a mammography screening.

Click to enlarge

You can see the so-called "false alarm" situation. This is the suspicion of cancer, on a mammographic image, but which will not be confirmed after further examinations. These additional examinations are sometimes heavy, and sometimes even result in biopsies, the number of which has greatly increased since the screening in place, this situation being favoured by the double reading. Experiencing a false alarm is often very stressful, as the woman has to wait sometimes several days or even weeks for confirmation of the absence of disease. For every 1,000 women over the age of 50 participating in screening for 20 years, there are an estimated 1,000 false alarms in France, leading to 150 to 200 unnecessary biopsies (Revue Prescrire, February 2015/Tome 35 N°376).

This is, along with overdiagnosis and radiotoxicity, the third harmful effect of mammographic screening.

False alarm and overdiagnosis aren't the same thing, don't confuse both !

What is an effective screening?

An effective screening involves two criteria:

• important reduction in mortality
• reduction in the incidence of advanced cancers

Example of a screening that meets these criteria, cervical screening, images from a presentation by Pr P.Autier

Click to enlarge

What about breast cancer? Is screening for breast cancer effective?

1°Criterion, mortality

Since 1996, there have been approximately 11,000 to 12,000 deaths from breast cancer per year. We are therefore not seeing the massive and drastic reduction that we observe in medicine when strategies really work. (The discovery of tuberculosis antibiotic therapy led to the closure of the sanatoriums within two years, the sterilization of the scissors used to cut the umbilical cords has effectively eliminated mortality from neonatal infections).
Furthermore, it is misleading to come up with figures for specific mortality (mortality from disease, here breast cancer) without giving figures for overall mortality (all-causes mortality).
Deaths due to the consequences of breast cancer diagnosis and subsequently due to surgical or anaesthetic accidents, complications of chemotherapy and radiotherapy such as cardio-vascular damages and radiation-induced cancers are not included in breast cancer mortality.
To date, there are no clear signs of a decrease in overall mortality from mammography screening.

As far as the specific mortality from breast cancer is concerned, we can see that it has been decreasing since 1993. However, this decrease occurred before the generalization of screening in France (in 2004) and cannot be attributed to it. In the United Kingdom, the decline in breast cancer mortality was 11% between 1985 and 1993, while screening was only operational in 1988.
In an impact report, a comparison of eight countries in Europe and North America reveals no correlation between national screening penetration and chronology or the extent of breast cancer mortality reduction. The comparative approach in this study with 14 other types of cancer shows a similar decrease in the mortality rate of these cancers, while these other cancers are not the subject of screening campaigns.
The start of the decline in breast cancer mortality is correlated with therapeutic de-escalation at a time when there is better control of the therapies administered to women and of their adverse effects.

There is a decrease in mortality from breast cancer, on the one hand it is not correlated with the screening practice, and on the other hand, by the very confession of official authorities data, 12,000 women continue to die of breast cancer every year, not counting those who die from complications that are distant from their treatment (12 146 in 2018 in France)..
Another fact is that mortality rates and survival are the same in groups of screened women and in groups of unscreened women, at similar stage of the cancer at the time of its diagnosis, as shown by several studies, including A.Miller's in particular, with a long follow-up of the groups of women over 25 years.

2°Criterion, the rates of serious cancers

The accumulation of epidemiological data shows that in populations where mammography screening has been widely used for a long time, the incidence of advanced cancers has shown little or no decrease. Numerous studies confirm this fact [1].
A recent, large 2015 study of 16 million women in the United States corroborates this disappointing finding [2]:
- No significant reduction in mortality (red line in the graph on the left)
- No reduction in serious cancers (red line in the graph on the right)

Survival at 5 years

This data, which INCa and screening promoters often advantageously highlight, is an indicator of the lifetime of cancer and not of the effectiveness of screening.
Early cancer diagnosis gives the illusion of a longer survival.
This is an optical illusion: by anticipating the date of the occurrence of cancer, one has the impression of an extension of the life, whereas life expectancy has not improved in any way.
The prolongation of survival is the result of two phenomena: the effectiveness of therapies that prolong the life of a patient with his cancer, and screening that anticipates the date of appearance of cancer regardless of the outcome of the disease.
Survival is increased all the more as the over-diagnosis is greater. Indeed, by definition, all over-diagnoses cure!

Click to enlarge

A good counter-example is the cervical cancer: its 5-year survival is very poor, but mortality from this cancer has fallen dramatically.

Comparison of 6 different screenings

Click to enlarge

While the incidence increases without any impact on serious cancers or significant reduction in mortality due to screening, this increase is then the direct effect of medical intervention which over-detects lesions, which is of no use to people's health.

For one cancer, we see that the contract is being fulfilled: this is the cervical cancer. Anticipating precancerous lesions means that the incidence of this cancer, the rate of severe forms as well as its mortality decrease perceptibly and is relatively well correlated with the introduction of screening.
However for the breast, prostate and thyroid, the situation is much more disappointing, with an unresolved problem: increasing overdiagnosis, without a satisfactory decrease in serious cancers or a reduction in treatment.
For colon cancer, it is currently recommended that screening be reserved for high risk individuals.

Bibliography

[1].Autier P, Boniol M, Koechlin A, Pizot C, Boniol M. Effectiveness of and overdiagnosis from mammography screening in the Netherlands: population based study. BMJ 2017;359:j5224.

Autier, M. Boniol, R. Middleton, JF Dore, C. Héry, T. Zheng et al. Advanced breast cancer incidence following population-based mammographic screening Ann Oncol, 22 (8) (2011), p. 1726-1735

Bleyer, HG Welch Effect of Three Decades of Screening Mammography on Breast-Cancer Incidence N Engl J Med, 367 (21) (2012), pp. 1998-2005

NA de Glas, AJ de Craen, E. Bastiaannet, EG Op ‘t Land, M. Kiderlen, W. van de Water, et al. Effect of implementation of the mass breast cancer screening programme in older women in the Netherlands: population based study.

Autier, M. Boniol, The incidence of advanced breast cancer in the West Midlands United Kingdom, Eur J Cancer Prev, 21 (3) (2012), pp. 217-221

Nederend, LE Duijm, AC Voogd, JH Groenewoud, FH Jansen, MW Louwman Trends in incidence and detection of advanced breast cancer at biennial screening mammography in The Netherlands: a population based study. Breast Cancer Res, 14 (1) (2012), p. R10

ML Lousdal, IS Kristiansen, B. Moller, H. Stovring, Trends in breast cancer stage distribution before, during and after introduction of a screening programme in Norway Eur J Public Health, 24 (6) (2014), pp. 1017-1022

RH Johnson, FL Chien, A. Bleyer Incidence of breast cancer with distant involvement among women in the United States, 1976 to 2009 JAm Med Assoc, 309 (8) (2013), pp. 800-805

Laura Esserman, Yiwey Shieh, Ian Thompson, Rethinking screening for breast cancer and prostate cancer, Jama, 302 (15) (2009), pp. 1685-1692

Jorgensen, PC Gøtzsche, M. Kalager, P. Zahl Breast Cancer Screening in Denmark
A Cohort Study of Tumor Size and Overdiagnosis, 166 (5) (7 mars 2017), pp. 313-323

HG Welch, DH Gorski, PC Albertsen Trends in Metastatic Breast and Prostate Cancer, N. Engl JMed, 373 (18) (2015), pp. 1685-1687

Di Meglio, RA Freedman, NU Lin, WT Barry, O. Metzger-Filho, NL Keating, et al. Time trends in incidence rates and survival of newly diagnosed stage IV breast cancer by tumor histology: a population-based analysis Breast Cancer Res Treat, 157 (3) (2016), p. 587-596`

[2] « Breast Cancer Screening, Incidence, and Mortality Across US Counties »
Auteurs : Harding C, Pompei F., Burmistrov D., et al. JAMA Intern Med. Published online July 06, 2015. doi:10.1001/jamainternmed.2015.3043

https://jamanetwork.com/article.aspx?articleid=2363025

The confusion between the two concepts is very often made. We must admit that the difference is not intuitive, and the concept of overdiagnosis is relatively recent.

So let's go back to the definitions.

FALSE ALERT (or false positive)

It is the suspicion of cancer on a mammographic image, which will not be confirmed after additional examinations.
A false positive is, therefore, a non-cancer that we know after performing examinations other than the mammogram.
These additional examinations that need to be done to invalidate the suspicion can be heavy and sometimes even result in biopsies, the number of which has greatly increased since screening was introduced, this situation being made more likely by the double reading performed in organized screening (a second radiologist examines the images taken in the first radiology center).
Knowing about a false alarm is often very stressful, as the woman must sometimes wait several days or even weeks for confirmation of the absence of disease, especially for biopsy results, where depending on the region, the delay is between a week and a month.

For every 1000 women over 50 participating in screening for 20 years, there would be about 1000 false alarms in France, leading to 150 to 200 unnecessary biopsies.
(Revue Prescrire, February 2015/Tome 35 N°376)

However, other assessments exist, giving higher figures. For example, here is an Australian evaluation ¹. It provides a result over 25 years, corresponding to the overall screening duration in a woman's life if she undergoes screening from age 50 to 74.

Excerpt from the book "Mammo ou pas mammo?" ed.Thierry Souccar

OVERDIAGNOSIS

Overdiagnosis is a real diagnosis of cancer. On a microscopic examination, there are cancerous cells, but the diagnosis is pointless for the woman because this cancer would never have impacted her life or health. It is not a misdiagnosis but a lesion that is unnecessary to detect.

How is it recognized? On an individual level, seeing a patient, we cannot know. For the attending physician, the pathologist, the radiologist, the surgeon, there is only one "diagnosis." That is why everything detected for a particular woman will be treated.
But on a population level, which is true for all screenings, epidemiologists note that there are always more cancer diagnoses in screened populations than in those not screened ². And that the greater the screening intensity in a population, the greater the number of diagnoses ³.

In the study cited in reference ², the Oslo researchers compared two groups of women of the same age; one was screened every two years, and the other was not screened and examined after 6 years. They found 22% more cancer diagnoses in the screened group (without counting carcinoma in situ, see the question on this subject). Moreover, with an identical mortality rate in both groups...
What can we conclude from this? If all cancer cells and all cancerous lesions were meant to become a "cancer disease," we would have the same rates of women with cancer in both screened and unscreened groups since both groups were composed of women with identical profiles. And there should have been a significant difference in mortality.
However, this is not what we observe. Therefore, when we do not seek them, some cancers do not progress or progress very slowly without impacting the person's life, and the person's immunity can control in such a way that there is no progression to cancerous disease. Having cancer is not synonymous with being ill with cancer.

Autopsy studies are also available. In autopsies of people who have died from causes other than cancer, we see that many people have cancerous lesions in their bodies that are unexpressed and dormant ⁴.

Yet what is the problem with overdiagnosis in breast cancer or other cancers? You might say that it is good to detect as many lesions as possible are detected...

The first problem is that over-diagnosis, i.e., a useless diagnosis made in a healthy person who is not complaining about anything, will inevitably be followed by over-treatment, which is useless by definition. The onset of a "disease" is declared as soon as a microscopic examination confirms the presence of cancerous cells.
Yet, cancer treatments are not harmless. They all carry risks, some of them fatal ⁵. The somewhat cynical argument that the woman will receive "lighter" treatment because a small lesion has been found is not acceptable. It is not a question of giving a woman a light treatment (the "lightness" of which, for those who have been through it, is relative) but of doing nothing if the woman did not need it.
The reduction in surgery remains to be proven. Moreover, wherever screening is carried out, mastectomies only increase, and in no case can we claim that women will have less surgery thanks to screening ⁶.

Our mini-video on overdiagnosis here: https://www.youtube.com/watch?v=Mr995i_Hetg&feature=emb_imp_woyt

The second problem is that if one accepts an overdiagnosis of a medical procedure with a potentially harmful effect, there must be a compensating beneficial effect for the population, for example, a drastic reduction in mortality, an impact on the overall mortality of the population, a drastic reduction also of the most serious and deadly cancers, and as we have seen above a very significant decrease in heavy surgical and radiotherapy procedures.
None of these expected beneficial effects of screening have been achieved... Serious cancers escape screening because they are often immediately disseminated as soon as they are detected, have intrinsically pejorative biological characteristics ⁷, and are rapid and voluminous at the time of diagnosis because they have a high growth velocity ⁸.

We invite you to refer here for a more detailed explanation.

The figures for overdiagnosis vary according to estimates and studies.
The best known and so far uncontested estimate is that of the independent Cochrane Collaboration, which you will find presented on our poster here.

This is the result of a meta-analysis, i.e., an analysis of the results of several studies (trials) carried out at a time when cohorts of unscreened women were available to compare them with cohorts of screened women (in the 1970s and 1980s).
In a population of 2000 women screened over 10 years, we can expect a prolonged life thanks to screening, but at the same time, 10 women are overdiagnosed.

Thus, many women must be screened over a long period to achieve a "life-saving" outcome, but at the same time, more cases of overdiagnosis are occurring. This means that women pay a heavy price for overtreatment, some of whom die. Some researchers also argue that the fatal effects of overtreatment accidents outweigh this meager benefit.⁹ According to Professor Baum, author of the referenced study, for every life saved, one life would be destroyed due to a fatal effect of overtreatment.

It should also be noted that this meta-analysis by independent Nordic authors is based on Canadian clinical trials, which were audited and confirmed to be free of bias.¹⁰

Thirdly, it is ethically unacceptable that, on the pretext that screening would save one woman in 2,000 over 10 years, another 200 to 400 women (false alarms) and another 10 women (overdiagnoses) should be harmed in return. This is ethically indefensible.
It doesn't matter how large the overdiagnosis is. It exists. And the percentage “battles” you can read in the press from one source to another are of little interest when a woman is concerned because it will always be 100% for her.
At the very least, women should be fairly informed.

The benefit-risk balance of screening is, therefore not, when the adverse effects (overdiagnosis, false alarms, radiation) are added up in favor of a predominant benefit because the reduction in mortality is not significant and is not attributable to screening (a decrease in cancer mortality was observed as early as the 1990s, with the improvement in treatment, therefore before the introduction of screening, and this was also the case for other cancers that were not screened, according to the impact studies)

The term "overdiagnosis" has become a real public health issue with the multiplication of routine examinations performed on healthy populations. It has been officially included in the thesaurus of references in the biomedical field.

Illustration in video, animated presentation of these two concepts:

Related links

These concepts are included in our decision support tool, which you can consult.

See also, How does cancer develop?

References

[1] Jolyn Hersch. Aide à la décision pour le dépistage du cancer du sein pour les femmes à partir de 50 ans. C’est votre choix. (Brochure australienne). Page 7. [En ligne : https://ses.library.usyd. edu.au/bitstream/handle/2123/16658/2017%20updated%20breast%20screening%20DA%20 (Hersch%20et%20al).pdf;jsessionid=F0396C69AD95F6431008EA16CB3B9195?sequence=1]. Consulté le 30 juin 2021.

[2] Zahl P-H, mæhlen J, Welch HG. The natural history of invasive breast cancers detected by screening mammography. Arch Intern med. 2008 Nov 24;168(21):2311–6.

[3] https://cancer-rose.fr/en/2020/12/29/analysis-of-harding-american-study-2015/
Harding C, Pompei F, Burmistrov D, Welch HG, Abebe R, Wilson R. Breast Cancer Screening, Incidence, and Mortality Across US Counties. JAMA Intern Med. 2015 Sep;175(9):1483–9.

[4] https://cancer-rose.fr/en/2020/12/29/frequency-of-incidental-breast-cancer-and-precancerous-lesions-in-autopsy-studies-a-systematic-review-and-meta-analysis/
Thomas, E.T., Del Mar, C., Glasziou, P. et al. Prevalence of incidental breast cancer and precursor lesions in autopsy studies: a systematic review and meta-analysis. BMC Cancer 17, 808 (2017). https://doi.org/10.1186/s12885-017-3808-1

[5] https://cancer-rose.fr/en/2021/03/02/heart-disease-is-the-biggest-killer-of-breast-cancer-survivors/

6] Our study about mastectomies in France https://cancer-rose.fr/en/2020/12/17/our-study-does-organized-screening-really-reduce-the-surgical-treatments-of-breast-cancers/

Our results are consistent with those found in other countries :

- In the United States, in a 2015 study of 16 million women, a 10% increase in screening activity was associated with a nearly 25% increase in lumpectomies and partial mastectomies (RR 1.24; CI 1.15-1.34), without a decrease in total mastectomies [8].

- In the United Kingdom, according to the 2013 Marmot report on breast cancer screening, the frequency of mastectomies is increased by about 20% in the screened population compared to the unscreened population [9].

- For all the randomized controlled trials worldwide that examined this issue in 2013, the Cochrane Collaboration estimates that the number of mastectomies is increased by 20% (RR 1.20; 95% CI 1.08-1.32) and the number of surgical procedures (mastectomies and lumpectomies) is increased by 30% (RR 1.31; 95% CI 1.22-1.42) [10].

[7] https://cancer-rose.fr/en/2020/12/17/are-small-breast-cancers-good-because-they-are-small-or-small-because-they-are-good/

8] https://www.youtube.com/watch?v=pbGZdyUCITc

[9] Baum M. Harms from breast cancer screening outweigh benefits if death caused by treatment is included. BMJ 2013 ; 346 : f385. doi : https://doi.org/10.1136/bmj.f385

[10] Bailar J. C, MacMahon B. Randomization in the Canadian National Breast Screening Study: a review for evidence of subversion. Canadian Medical Association Journal. Jan 15, 1997;156(2):193-199.

Overdiagnosis is defined as the histological (i.e. by means of a microscope) diagnosis of a "disease" which, if it had remained unknown, would never have caused any inconvenience to the patient's health during her lifetime, or threatened her life.
It is not a misdiagnosis or a false alarm. It is really cancer in view of its current definition, which is based solely on the diagnosis under the microscope of a sample taken from an organ (the breast) .
The diagnosis is correct but needless to the patient. It is the medical practice that produces this excess of "diseases". Indeed, having cancer cells which were detected does not make the individual as being cancerous. But the more we detect, the more we find.
Its reality is absolutely irrefutable nowadays, its demonstration is based on epidemiological studies with a high level of evidence, it is an accounting reality, wherever screening exists; overdiagnosis is not identifiable at the individual level, because for the concerned individual, or for the doctor who detects the presence of cancerous cells, it is a diagnosis. Overdiagnosis is revealed by comparing populations subjected to different screening intensities.

Which evidence for overdiagnosis of breast cancer?

First of all, several comparative studies, including a fundamental study by the Oslo Institute in 2008 (Zahl P-H, Maehlen J, Welch HG. The natural history of invasive breast cancers detected by screening mammography. Arch Intern Med. 2008 Nov 24;168(21):2311-6).

Two groups of women were compared, one screened every two years, the other examined only once after six years. Result: 22% excess cancers in the screened group. Thus, if all the tumours evolved into perceptible cancers, we should have found the same number of cancers in these two groups of women with the same profile. Since more cancers are found in the group screened every two years, it means that there is an excess of diagnoses.

Autopsy studies further corroborate this result. Almost half of the women (the percentages vary according to age group), who died of causes other than breast cancer, had unexpressed breast lesions. The same phenomenon can also be observed in men in their prostate, which is why systematic screening for prostate cancer is no longer recommended by the High Authority for Health.
Read: https://cancer-rose.fr/en/2020/12/30/arc-classification/

The problem with over-diagnosis is that it is accompanied by overtreatment, all without any gain in survival for women, there is no difference in mortality figures between the groups of screened and unscreened women.
However, the presence of more and more diagnoses of breast cancer that would never have manifested themselves, makes it possible to justify the apparently positive results of this health system in the eyes of the promoters of screening and the health authorities.
By detecting "harmless" cancers, screening gives the illusion of contributing to cures. With the overdiagnosis generated, screening makes patients believe that it is effective when they present a cancer that has been proven by microscopic examination, but which will not impact their health (these overdiagnosed cancers remain quiescent, do not progress or progress only slightly or regress).
Thus, by selecting non-ill women, screening justifies a treatment and gives these women the illusion of curing them of a disease they would never have had without it.

Therefore it is the massive screening that generates overdiagnosis and "feeds" on it to convince the medical profession and public opinion of an effectiveness that is not proved.

Overdiagnosis is a source of considerable harm to women who undergo screening mammography. Recognition of the concept of overdiagnosis of cancer by the medical community has been slow, but today it is no longer acceptable to minimize its burden, nor its consequences, and continue to not inform the main interested parties.

Probably in 10 years' time, if we continue in this way, one woman out of six will be diagnosed with breast cancer during her lifetime, perhaps even more since a woman labelled "cancerous" represents herself a family risk factor for her offspring, who will be even more encouraged to be screened. With the certainty that the overall harm induced by screening will only increase…

What are the consequences of overdiagnosis?

The consequences are those of an overtreatment. All lesions, overdiagnosed or not, will be treated.
Women will suffer the consequences of the side effects of treatment.
Mastectomies increase in all countries with screening-campaigns.
Radiotherapy presents the risk of causing secondary radiation-induced cancers and increases the risk of coronary artery disease when the left breast is irradiated.
Chemotherapy has known adverse effects on the blood lines, which can lead to nausea, vomiting, hair loss, induced menopause etc…
Hormonal therapy then administered for 4 to 5 years to reduce the risk of recurrence, in the case of hormone-receptor-positive cancers, can be well tolerated, but can also cause fatigue, arthralgia, thromboembolic complications and, in the case of Tamoxifen, increase the risk of endometrial cancer (uterine mucosa).
All of these effects have a profound impact on the emotional, social, professional and economic life of women and on their physical and mental health.

Click on picture to enlarge

What does the "survival" term mean, and first, what does it not mean?

• Being alive 5 years after diagnosis does not mean being cured.
• Survival has no impact on longevity or life expectancy, which are unaffected by improved survival.

Consider a woman with a life expectancy of 65 years.

• A 90% survival rate at 5 years means that 9 out of 10 women will be alive after 5 years. But this is only the case for cancers that can be detected at an early stage, for those less aggressive.

Cancers with aggressive and progressive characteristics cannot be detected at an early stage, which would significantly improve their management, so survival rates are much lower…

A well-known bias that improves survival artificially.

This is known as "lead-time bias."

Survival is defined as the length of time a patient lives while being knowledgeable of his cancer. We anticipate the "start point" of cancer that would have manifested itself later in the absence of screening. The life expectancy of the patient with his cancer thus appears longer.

Here is a diagram to understand [1]:

To use an analogy:

A train traveling to Paris derails in Orleans at 3 pm and causes the death of many passengers. If you get on that train in Bordeaux, you will live another three and a half hours. If you get on that same train in Tours, you will live another 30 minutes. However, your train will always derail at 3 pm.

Or better, let us use an analogy from Pr Michael Baum in a letter published in The Times, March 24, 2019

"Lead time reflects a frame shift in observing the natural history of the disease that can be understood with this analogy. If you get on a train bound for Edimburgh at Durham that crashes at Newcastle you live for 20 minutes yet if you board the same train at King Cross you live for two and a half hours. Over diagnosis results from the detection of sub-clinical foci of  disease that microscopically look like cancer yet are not programmed to progress. These account for about 30% of screen detected "cancers" that are then over-treated by surgery, radiotherapy and chemotherapy, all of which have toxic consequences."

Survival depends mainly on two parameters that amplify it

1°- Therapeutic efficacy

The accumulation of epidemiological data provides, especially since 2015, strong evidence that improvements in patient management have played a significant role in the reductions in breast cancer mortality observed in Europe, Oceania, and North America, while the role of screening mammography is marginal.

While survival is an inappropriate criterion for measuring the effectiveness of screening, it remains the most widely used and most likely relevant marker for assessing the efficacy of a therapy.

2° - Overdiagnosis

The more lesions are overdiagnosed, which by definition do not cause death, the more lesions that would never have led to death are detected and counted, and the more survival will tend to be 100 %.

Let's use an analogy here as well.

If we treat all of the minor winter colds with triple antibiotic therapy, we can claim we have saved all patients from severe pneumonia. However, we know that the vast majority of seasonal colds heal on their own without the use of antibiotics. This is a misleading embellishment of the effect of human action, presenting it as beneficial when the counterpart will be the induction of numerous drug resistances.

Where does the 99% survival figure come from?

The figures come from American data from the American SEER program [2], but this survival is not the same depending on the stage of cancer:

- localized breast cancer: 99% survival at 5 years

- breast cancer with regional spread: 86% survival at 5 years

- breast cancer with distant metastases: 29% survival at 5 years.

When it is stated that the 5-year survival rate for breast cancer is 99 percent, it leads one to believe that 99 percent of cancers will be cured with screening. However, as we can see above, survival is better in the early stages than in the advanced stages; these advanced stages would benefit from early detection, but the real question is: is screening able to avoid the advanced stages?

Severe forms of cancers are often dangerous from the start, and because they are inherently aggressive, they progress quickly, so screening misses them [3]. Screening is more likely to detect too many small, non-progressive, and non-threatening cancers, many of which are not necessary to detect. This ability to detect essentially non-progressive cancers increases overdiagnosis by creating the illusion of cures for lesions that would not have killed anyway and thus artificially improves survival rates.

Increased survival with no benefit to women

The two diagrams below (reproduced with the author's kind permission [4]) show how survival is “improved” with increasing overdiagnosis, without any benefit in terms of mortality for women.

Caution, this is a hypothetical scenario used to demonstrate how a survival rate can vary significantly depending on the extent of overdiagnosis. However, it shows how closely linked the two parameters are; the more significant the overdiagnosis, the greater the "improved" survival rate.

If survival is not a good criterion for screening effectiveness, then what are the good criteria?

The three main criteria for screening effectiveness are:

- a significant decrease in specific mortality

- the decrease of advanced forms of the disease

- the decrease of the heaviest treatments.

In conclusion

1. Localized cancer survival is excessively optimistic due to increased overdiagnosis and the resulting illusion of cure.

2. Survival would indeed be better in advanced forms, but screening is unable to detect them in time.

3. Survival is not a good marker of the effectiveness of screening but of the therapy efficacy.

References

[1] https://apps.who.int/iris/handle/10665/330852

[2] The Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NCI) is a source of epidemiologic information on cancer incidence and survival rates in the United States.

[3] https://cancer-rose.fr/en/2020/12/17/are-small-breast-cancers-good-because-they-are-small-or-small-because-they-are-good/

[4] https://www.armchairmedical.tv/media/The+Lisa+Schwartz+Reading+Steve+Woloshin/0_1y9lo5q5

Ductal carcinoma in situ (DCIS) of the breast is defined by the proliferation of cancer cells within a galactophoric duct without these cells protruding beyond the wall of the duct, to spread to the rest of the breast.
It is essentially of mammographic finding, in fact 90% of women diagnosed with DCIS (ductal carcinoma in situ) had microcalcifications at mammography. In their vast majority, these lesions do not threaten women's lives if they are not detected, their prognosis is very good, survival at 10 years, the mostly used measure by the health authorities, is over 95%. There are the ductal form and the lobular form, the latter considered to be rather a risk factor for breast cancer. DCIS largely contribute to overdiagnosis. Tests and studies indicate that the increasing detection of DCIS has not led to the reduction of breast cancer mortality. Before the era of screening, DCIS accounted for less than 5% of all breast cancers, rising to 15-20% in all countries where screening campaigns are taking place. They are not included in the incidence figures (rate of new cases) reported by the National Cancer Institute, as they are considered separately, and not as "real" cancers. In addition, there is a lack of real consensus among pathologists regarding the classification of these lesions when analyzing the biopsies they receive, with a tendency to overclassify them into more unfavorable prognosis categories, due to the fear of underestimating a "disease".

Most DCIS are considered as non-mandatory precursor lesions toward invasive cancer; paradoxically, the spectacular increase in their detection and their subsequent surgical excision has not been followed by a proportional decrease in the incidence of invasive cancers. The major problem is that these particular entities of breast cancer are treated with the same severity as breast cancer.

In November 2016, a study conducted by University of Toronto concluded the following:

• Their treatment makes no difference to women's survival. - Women with DCIS are heavily treated (sometimes by bilateral mastectomy) and have the same probability of dying from breast cancer as women in the general population.
• Preventing recurrences by radiotherapy or mastectomy would therefore not reduce the risk of breast cancer mortality.

Similarly, our study of mastectomies in France found a steady increase in surgical procedures, our first hypothesis being the overtreatment of lesions that are not invasive cancers, but rather so-called pre-cancerous lesions and DCIS [1] [2].

The long-term consequences of over-treatment can place women's lives at risk. Radiation therapy for these lesions, for example, appears to be ineffective in reducing the risk of death from breast cancer, but it is associated with a dose-dependent increase (from 10 to 100% over 20 years) in the rate of major coronary events [3].

Moreover, in several countries clinical trials are being conducted to test simple active surveillance, particularly for low-grade CIS, rather than aggressive treatment:

• COMET(US)
• LORIS(UK)
• LORD(EU)*

For Philippe Autier [4], of the International Prevention Research Institute (IPRI), the problem is definitely inherent to routine mammography, in particular to digital mammography, which is too efficient in detecting small calcifications; these are the most frequent radiological sign of these forms, and mammography has an excellent sensitivity for the detection of these microcalcifications.

To summarize, in populations screened the incidence of DCIS rises from 1-20% with no corresponding fall in "later stages" nor invasive cancers. Also DCIS is often multifocal demanding a mastectomy yet multifocal invasive cancers are very rare. Read more : https://cancer-rose.fr/en/2021/01/20/carcinoma-in-situ-the-problem-of-its-overdiagnosis-in-screening-mammography/

*For the LORD trial https://www.dcisprecision.org/clinical-trials/lord/ trial, here is some information:
-Since February 2019 are also accepted DCIS Grade II, in addition to Grade I
-Since July 2020, the randomized trial has been transformed into a patient preference trial: women have the choice of the trial arm (either surveillance or conventional treatment)
-Estrogen receptor and HER2 testing has been added before patients are enrolled in the trial to rule out high-grade lesions, to make the trials safer
-There are now 28 sites open in the Netherlands, 6 in Belgium, and 15 sites will open in other countries, including France, coming soon!

In France:

In France, it is not recommended to offer patients simple active surveillance as an alternative to local treatment, which consists of surgery, followed or not by radiotherapy.

The 2015 French recommendations do not retain any indication for abstention from surgical excision in the management of DCIS.

In 2015, the French National Cancer Institute (INCa) published new recommendations for the management of DCIS that advised surgical removal of lesions, by lumpectomy or by mastectomy in case of extensive lesions, mastectomy that will also be advised when the lesions are multiple, or the DCIS is found in the breast concomitantly with another atypical lesion or a "border lesion." Radiotherapy is frequently recommended after conservative surgical treatment to reduce recurrence.

But these proposed approaches are standardized and do not consider the multitude and heterogeneity of histological lesions and clinical situations. In recent years, the scientific literature has been enriched by data that allow to discuss the benefits of de-escalation in certain situations. In the future, practices will have to be more individualized.

References :

[1] https://cancer-rose.fr/en/2020/12/17/our-study-does-organized-screening-really-reduce-the-surgical-treatments-of-breast-cancers/
[2] https://cancer-rose.fr/en/2020/12/17/explanation-of-our-study-on-mastectomies-in-france-carried-out-by-cancer-rose/
[3] SC Darby, M. Ewertz, P. McGale, AM Bennet, U. Blom-Goldman, D. Bronnum, et al.
Risk of Ischemic Heart Disease in Women after Radiotherapy for Breast Cancer
N Engl J Med, 368 (11) (2013), p. 987-998
[4] https://cancer-rose.fr/en/2020/12/17/mammography-screening-a-major-issue-in-medicine/

For more information :

A blog : https://dcis411.com/

UPDATED on November 5^th, 2022

Microcalcifications are small calcium deposits in the breast that are becoming increasingly common with the progress of mammography technology.

When they are detected, their shape, number, grouping, topography (localization in the breast), size, morphology, and morphology of their grouping are examined.

Calcifications can be intra-galactophore (in the breast milk ducts), vascular (in the vessels of the breast), located in the epithelium bordering the breast milk duct, or in the supporting tissue of the breast.

In mammographic practice, three main situations can be identified: typically benign calcifications, typically malignant calcifications, and intermediate conditions. Of course, the clinical context must be considered when determining malignancy or benignity based on the images. For example, a clinically and ultrasonographically malignant nodule with a few non-concerning calcifications at the edge should not lead to ignoring the other arguments of a suspicious lesion. In contrast, if nothing clinically significant but very concerning calcifications are present, they should prompt further examinations and, if necessary, a biopsy.

The BI-RADS classification of your breast examination will be determined by the presence of microcalcifications and their morphology.`
BI-RADS 2 means typically and with great certainty benign calcifications.
BI-RADS 4 and 5 require a biopsy because they are most probably (for ACR 4) and definitely (for ACR 5) malignant.
BI-RADS 3 represents a situation that is not typically malignant but requires follow-up and rechecking, such as a cluster of calcifications that did not previously exist or an existing cluster that has changed slightly.

We will see later the difficulties and pitfalls of these situations.

Calcifications in systematic mammography:

They are present in 30% of mammograms ! They are the source of the detection for:
- 70% of small invasive cancers less than 5 mm
- 90% of in situ cancers
Later in the article, we will come back to the in situ lesions and explain what their detection on mammography means for a patient.

ACR 2 - almost certain to be benign

► They follow the morphology of an identifiable anatomical structure:
► Macrocalcifications: an adenofibroma, a cyst wall, a secretory ductal ectasia, a plasma cell mastitis, a vessel, a surgical scar.
► Sedimented macro or arciform microcalcifications (often in microcysts).
► Cutaneous microcalcifications.

ACR 5 - almost certain malignant

Highly suspicious abnormality, requiring surgical excision.

► Vermicular, arborescent, branch-like microcalcifications...
► Opacity with microcalcifications within it
► Grouped microcalcifications that have increased in number from one check to the next
► Grouping calcifications follow a galactophoric path or are arranged in a triangle as if following an area of galactophorous ducts.
► The gradation in size and density from the center to the periphery of a cluster of calcifications with a dirty washed-out appearance of the more distal calcifications is a highly suggestive sign of malignancy.

ACR 4 - probably malignant

These are abnormalities considered indeterminate or suspicious and requiring histological verification:

* Numerous regular punctiform microcalcifications and/or grouped in clusters that are neither round nor oval
* Dusty microcalcifications, numerous and clustered
* Irregular, polymorphic microcalcifications, few

ACR 4 means that there is a suspicious abnormality that should be checked. Sometimes it is cancer, but not necessarily. ACR4, therefore automatically implies a biopsy under ultrasound (micro-biopsy). For microcalcifications that are only visible on X-ray, this will be done under X-ray control via a procedure called mammotome (macro-biopsy) or sometimes directly by biopsy-exeresis if the cluster is small enough to be removed entirely by mammotome.
We suspect cancer, but we could be mistaken, or it could be a slow-growing or aggressive form of cancer. The image that prompted us to define it as ACR4 tells us nothing about the aggressiveness of cancer if the biopsied material is indeed cancer!
Because of these uncertainties, this ACR4 classification has been subdivided, with a range of cancer probability assigned to each subdivision.

But what about calcifications other than ACR 2 and ACR 5?

This is where things get complicated.
None of the following features:
-round or oval shape of the cluster
- the presence of multiple clusters of identical morphology
- stability over time
► are sufficient to assure with absolute certainty of benignity.

The multifactorial nature of the information to be synthesized makes any strict classification impossible. There are infinite varieties of transitions for each description. The shape, the size, and the number depend on the technique, the information material, and the breast density. Attempts at coding have failed, and we are now faced with a very big problem of dealing with these intermediate images, which are not always known with certainty.
In these situations, the "expert" readers and reviewers only agree in half of the cases.
Frequently, women are subjected to closer "monitoring," more X-ray images, and many consultations. They all attest to the stress and inconvenient nature of these frequent tests, which need their availability and organization in their professional activities, which is constraining. With the increase in anxiety generated by the numerous so-called "awareness" campaigns, with media slogans such as "every minute counts," the wait-and-see attitude that consists of following up and rechecking the sites of microcalcifications (according to what is generally recommended, once every 6 months and then once every year *) is increasingly being abandoned.

Currently, we see in practice that the ACR 3 classification (surveillance) is gradually disappearing in favor of an over-classification "just in case" towards ACR 4.

ACR 4 is now a true catch-all that will determine and justify for the patient a histological confirmation, and so a biopsy, along with the placement of a localization clip, just in case of further surgical intervention.
In fact, due to the increased concern of the doctor, who fears legal action if he does not alert the patient immediately, and the patient, who believes that even the slightest delay could cost her life, the examination is readily upgraded from ACR 3* to ACR 4. Consequently, the number of percutaneous biopsies has increased exponentially.
Simultaneously, the biopsy yield (the number of tumors diagnosed / number of biopsies performed) has declined to approximately 30%. Before less than ten years ago, it exceeded 50%.

* The French referential (page 21) is as follows:
Lesions classified as ACR 3 = No indication for systematic biopsies. However, close monitoring is necessary: monitoring at 6 months for calcifications and at 4 months for masses - In the event of stability during this first follow-up => new close evaluation at 1 year, then at 2 years from the initial examination:
-Stability of the lesion over 2 years enables reclassification as benign, ACR2.
-The lesion is classified as at least ACR4 if there is an increase in size (>10%) or appearance of pejorative morphological characteristics during this follow-up.

Even though mammography has a higher sensitivity for calcifications, these calcifications may be detected for the first time on the initial x-ray. There is a temptation to promptly do a biopsy to provide reassurance, resulting in needless exams, false alarms, and considerable patient stress.

In other words, more and more benign lesions are being biopsied when a simple follow-up and recheck would have ruled out cancer.

Summary of the ACR classification of calcifications.

Positive predictive value (PPV) is the probability that the screened woman is really ill when the screening test is positive. This answers the question, "Doctor, with this abnormality discovered, what is my risk of developing breast cancer?"

The case of carcinoma in situ

This is essentially a mammographic finding. Mammography reveals microcalcifications in 90% of women with DCIS (ductal carcinoma in situ). If not detected, the vast majority of these lesions are not life-threatening. Their prognosis is excellent, with a 10-year survival rate (a parameter widely used by health authorities) of more than 95%. There is a ductal form and a lobular form, rather considered a risk factor for breast cancer.

DCIS is a significant contributor to overdiagnosis. DCIS is treated as "real" cancer in France by surgery and radiotherapy (French referential page 55).

According to trials and studies, increased detection of DCIS has not reduced breast cancer mortality. DCIS accounted for less than 5% of all breast cancers before the screening era, but this has increased to 15-20% in all countries where screening campaigns are in place.

What about MRI?

Because of its low specificity (probability that the screening mammogram remains negative when the screened woman is not ill), MRI, especially in young women, can be positive for calcifications when the patient does not have cancer.

This examination can produce false positives for benign breast abnormalities (various mastopathies) or false negatives despite the presence of carcinoma in situ.

The MRI is inappropriate for microcalcifications.

Images

A course

For those interested, for midwives, doctors, and students, the course given by Dr. Bernard Duperray, former Head of the Imaging Department at Saint Antoine Hospital, Paris: https://cancer-rose.fr/2021/02/24/cours-calcifications-du-sein/

And also: https://cancer-rose.fr/2021/02/24/fausses-microcalcifications/

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

-Local effects, more or less late :

Cutaneous effects, simple redness even radiodermatitis.

Pulmonary fibrosis causing the lung tissue to lose its elasticity.

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

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

-General effects :

Fatigue

Anaemia

Inappetence

Decrease in the number of blood cells

INDIVIDUAL RADIOSENSITIVITY

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

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

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

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

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

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

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

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