Example of predispositions to breast and ovarian cancers

Alterations of the BRCA1, BRCA 2, PALB2, and RAD51 genes (and other less frequent ones) increase the risk of breast and ovarian cancer. 

"With a 12% lifetime risk of developing breast cancer - most often after the age of 50 - all women are at risk of breast cancer. However, women with an alteration of the BRCA1 gene have a 72% risk of developing breast cancer and 44% of ovarian cancer at the age of 80. For women with an alteration on BRCA2, the risks are respectively 69% and 17%," specifies Dr. Dominique Stoppa-Lyonnet, head of the Genetics Department of Institut Curie, who in 1991 created one of the first genetic consultations dedicated to predispositions to breast cancers. 

It is estimated that 120,000 women could be predisposed to breast cancer in France. Among the criteria for referring a patient with breast or ovarian cancer to a genetics consultation, there are family criteria (presence of several breast and/or ovarian cancers in the same family branch, and all the more so if the diagnosis was made before the age of 50), but also more individual criteria: for example, diagnosis of breast cancer before 41 years of age or triple negative breast cancer before 61 years of age, or high-grade ovarian cancer regardless of age, or diagnosis of breast cancer in men. These criteria are constantly evolving. 

Monitoring of women with a genetic predisposition is mainly based on the performance of medical examinations – MRI and mammography - in order to detect the occurrence of cancer as early as possible. 

"In France, approximately 10% of the affected women prefer to have preventive removal of the mammary glands. For women older than 40 years of age, removal of the ovaries is recommended for those with a predisposition related to the BRCA1 gene. This recommendation is postponed to 45 years in a BRCA2 context." Prof. Dominique Stoppa-Lyonnet. 

These decisions are not easy to make, and a multidisciplinary team composed of gynecologists, surgeons, plastic surgeons and psychologists is available within a follow-up support network to support these women in their decisions - whatever they may be. 

To date, the follow-up is approximately the same for all women with an alteration. Knowledge of the individual risk of developing a tumor still needs to be refined. To this end, Nadine Andrieu and Fabienne Lesueur, managers of the Genetic Epidemiology of Cancer team (Inserm/Institut Curie) are conducting several studies. "The identification of the BRCA1 and BRCA2 genes has greatly contributed to improving the understanding of predispositions to breast cancer. However, several biological and epidemiological arguments suggest that environmental or lifestyle factors, and in particular gyneco-obstetric factors, can modify the cancer risk associated with mutations in these genes," note the researchers. The discovery of these risk factors will ultimately allow for a better estimation of individual risks and for customizing the screening and follow-up strategies.