Category: Questions – Short Answers

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

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

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

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

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

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

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

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

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

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

There are several methodological flaws on Mypebs study :

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

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

FIRST

What is a "family at risk"?

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

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

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

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

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

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

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

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

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

-One person with ovarian cancer

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

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

Eisinger score

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

We present it below (downloadable):

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

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

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

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

B- No mutation found in women with breast cancer.

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

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

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

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

REMEMBER THE FOLLOWING:

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

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

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

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

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

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

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

First of all, who are the subjects at risk?

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

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

-affected male relative, first or second degree

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

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

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

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

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

The conclusions are:

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

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

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

Three cases are studied:

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

Lesions referred to as "at risk"

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

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

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

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

What about "doing nothing?"

Screening should remain a personal choice

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

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

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

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

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

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

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

This is a very personal decision

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

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

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

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

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

What is at stake?

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

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

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

What we know:

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

So, what should women do in the meantime?

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

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

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

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

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

Health Policy

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

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

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

Références

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[1] https://cancer-rose.fr/en/2017/11/20/what-is-high-risk/

[2] https://cancer-rose.fr/en/2021/03/29/what-is-an-effective-screening/

[3] https://cancer-rose.fr/en/2021/03/27/what-is-overdiagnosis/

[4] https://cancer-rose.fr/en/2021/03/28/what-is-survival/

[5] https://mypebs-en-question.fr/actus/duggan_lancet_en.php

[6] https://cancer-rose.fr/en/2021/03/29/what-is-an-effective-screening/

[7] https://cancer-rose.fr/en/2021/03/30/what-is-a-screening-mammogram/

[8] https://cancer-rose.fr/en/2021/03/29/what-is-an-effective-screening/

[9] https://cancer-rose.fr/en/2021/03/27/what-is-overdiagnosis/

[10] https://cancer-rose.fr/en/2021/03/28/what-is-survival/

[11] https://cancer-rose.fr/en/2020/12/17/our-study-does-organized-screening-really-reduce-the-surgical-treatments-of-breast-cancers/

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

[13] https://jme.bmj.com/content/47/7/510?utm_source=alert&utm_medium=email&utm_campaign=jme&utm_content=toc&utm_term=24062021

[14] https://cancer-rose.fr/en/2021/09/04/screening-campaigns-a-move-toward-greater-caution/