JANUARY 18, 2021
(We have addressed this specific topic in two articles, below is a practical summary at the request of one of our readers. [i] [ii])
The first problem is to define a woman who is at high potential risk of developing breast cancer during her lifetime. And what is a "family at risk".
A family history alone, even a direct one, does not constitute the proof of being a person "at risk", contrary to what is often presented as a scarecrow to women.
We receive plenty of testimonials from young women who are unnecessarily alarmed and above all incited to unnecessary and dangerous over-medicalization.
What about the search for genetic mutations in women? When should it be done?
This is the question that the independent French medical journal Prescrire addressed, Volume 36 N°388/February 2016.
Genetic mutations in the BCRA1 and BCRA2 genes are autosomal dominant, and women with these mutations are at higher but earlier risk of breast and ovarian cancer than the general population.
-The median age of onset is 40 years and the cumulative risk of cancer at age 70 is 51% to 75% for the BRCA1 mutation,
-The median age is 43 years and the estimated cumulative risk is 33% to 55% for the BRCA2 mutation.
The journal Prescrire proposes the following criteria as significant backgrounds for proposing an onco-genetic consultation:
-Three people from the same branch, with breast cancer before the age of 70,
-Two people in the same branch, with cancer before the age of 50
-A person who has had ovarian cancer
-A person with breast cancer with a diagnosis before the age of 40, or a bilateral form, the first one before the age of 50, or a hormone receptor negative cancer that occurred before the age of 60.
The Eisinger score is a decision aid for requesting an onco-genetic consultation.(Click below to download) :
Several situations can arise in families with multiple cases of breast cancer:
A- Mutation identified in a woman in the family, presenting a breast cancer.
This search for genetic mutation brings valuable information to the women in the family: women who are carriers have a higher risk, women in the same family who do not have it, end up with the risk of the general population.
If a woman in the family decides to do a mutation search on the BCRA1 or BCRA2 genes because of a loaded genealogy, and finds herself carrying a deleterious mutation on these genes, then her risk of developing breast cancer appears to be high, and this risk is also very high for relatives.
B- No mutation found in women with breast cancer.
Either there is really no mutation and the patient has developed a form of cancer without a genetic cause, or there is a mutation, but it may be due to an unidentified genetic cause.
Therefore, there will be uncertainty for the women in her family regarding the hereditary nature or not of this cancer, the risk of the familial nature of this cancer is not as high as in the case of an identified mutation such as BRCA but probably slightly higher than in the general population.
Uncertainty makes it necessary to analyze genealogy, which also has its share of uncertainties and imprecisions…
C- The person with breast cancer has not done any genetic research.
For the women among the relatives, this gives useless information: either the ill person may have had a mutation that was not researched, or she is free of a mutation but the mutation possibly exists in the family members.
All overall, the following points should be kept in mind:
- Either the person presents a family case carrying a mutation but she is free of any mutation herself, her risk will be close to that of the general population.
- Or the person has the mutation and can be estimated to have a higher risk of breast cancer than the general population.
- But for other women there are still uncertainties about their family's risk of breast cancer:
-In women whose family members have had breast cancer but without a mutation found in only one of the family cases,
-In women with a personal genetic research of a mutation that is negative, with a genealogy presenting several cases of breast cancer, but without research done on the ill persons.
Proposals of conduct to be followed, different options depending on the situation
Who are the individuals with the highest theoretical risk?
-Woman with a case of breast cancer in a first-degree relative (mother, sister, daughter) before the age of 40.
-Two women with breast cancer in the family of first or second degree.
-Male relative with breast cancer in the family of the first or second degree
-First or second degree female relative with ovarian cancer.
Summary according to the Prescrire dossier published in the Revue Prescrire May 2016/Tome 36 N°391-p.355 to p.361
Here is a table summarizing the proposed courses of action according to the presence of mutation or not, and proposals for complementary imaging (downloadable table, click below):
EXISTING RECOMMENDATIONS IN FRANCE
1°In 2014, the French National Authority for Health (Haute Autorité de Santé) issued recommendations that are still in force:
2° The recommendations of the National Cancer Institute, click (table p.10 of the doc)
As you will read, early and annual mammography is recommended, ignoring the greater risk of radiation-induced cancer, which can occur, depending on mutations, as early as the first mammogram. iii] [iv]
For these women at particular risk, recommendations are made without any objective data on the impact of different screening strategies, on overall mortality data, breast cancer mortality, mastectomies, treatment effects, over-diagnosis and false alarms for this at-risk population. In absence of data, these women and their caregivers are unsure of what to do and are struggling empirically.
While assessments are conducted on the general population, it is equally important to do them in these special populations, but they are not available.
A thorough discussion should be undertaken with the patient because the knowledge of this high risk will condition for her, in addition to an important psychological burden:
-Numerous false alarms (false positives)
-Over-diagnosis is highly probable but not evaluated since no studies have been carried out to quantify it.
To quote the May 2016 issue of the journal Prescrire: "To ensure that screening has a favorable benefit-risk balance, it is not enough to determine the most effective detection method: earlier diagnosis does not always change the burden of treatment for patients, nor necessarily the prognosis of the disease".
"It is also necessary to establish the conditions where this translates into tangible clinical benefits for the people screened. It is also important to measure the undesirable effects to which all screening exposes people: over-diagnosis and over-treatment, sources of serious undesirable effects sometimes; iatrogenicity of the tests; false positives causing anxiety and useless tests; medicalization of the healthy person's existence. »
And further on, on the ethical aspect:
"Ethics. The magnitude of the risk of breast cancer in these higher-risk women compared to the general population does not make it unethical to conduct randomized clinical trials, on the contrary. Clinical trials comparing the effects of various screening strategies on clinical criteria such as total mortality, breast cancer specific mortality, frequency of breast amputations, frequency of cytotoxic treatments, would provide the answers that are lacking, instead of leaving women and caregivers without solid evidence for these important decisions".
According to the journal Prescrire, a U.S. evaluation reports 125 cases of radiation-induced breast cancer per 100,000 women between 40 and 74 years of age screened by mammography every year, 16 of which are fatal. And for high-risk women, it has been shown that breast cancer was twice as frequent in women exposed to x-ray examinations before the age of 30 than in those not exposed.
Other complementary exams
Other exams than mammography, each having its limits, and an adapted follow-up can be proposed.
This exam has a higher sensitivity compared to mammography and is less radiating.
MRI + Mammography:
84% of cancers found
75% of cancers found
32% of cancers found
These proportions are almost identical for women at high risk, but here the problem is the same, we do not know the proportion of overdiagnosis. It is not known whether there is a gain in survival for these women who are followed in this way, or whether, on the contrary, they are exposed to more overdiagnosis and invasive treatments.
The long-term effects of Gadolinium injected annually are also unknown. The assessment of this potential risk is all the more necessary as these women will be integrated into heavy surveillance protocols, with multiple repeated MRI scans.
This product has possible side effects during injection and some cases of allergic reactions have been described.
this examination increases overdiagnosis and exposes to false positives and multiplies unnecessary biopsies.
Clinical examination by a professional:
The authors of the Prescrire dossier did not find any study evaluating the performance of breast self-examination.
But according to all the studies examined by the authors, it seems that at least half of the cancers discovered by an imaging examination were not diagnosed by the clinical examination carried out at the same time. It is not known if a delay in clinical diagnosis would be life threatening, as this has not been evaluated.