Clinical and social importance of follow-up assessment of family members of patients with BRCA mutations.

Abstract

10621 Background: The identification of BRCA1 and BRCA2 genes mutations are of paramount importance in the treatment and follow-up of hereditary cancer patients. When a pathogenic variant (PV) is identified in one of these genes, the surveillance for new primary tumors becomes individualized. When a pathogenic mutation is identified other family members may also be at high risk for developing tumors. Then the investigation should become familiar. Methods: This study reports the experience of a public oncogenetics service with the identification and follow-up of relatives of patients with BRCA mutations. Of the 1505 patients registered, 773 are probands, of which 71 had a mutation in one of the BRCA genes. A total of 503 family members were evaluated, with an average of 13 relatives per proband. Results: Of the 353 relatives with a BRCA1 mutation, 132 had the familial mutation, and only 18 had cancer diagnosis. The mean age of the evaluated family members was 37 years, lower than the mean age at diagnosis of the probands, which was approximately 41 years, two founder mutations in BRCA1 (NM_007300.4:c.3331_3334del and NM_007300.4:c.211A > G) were more recurrent among index cases, which is associated with the ancestral background of the local population. For the BRCA2 gene, 148 family members were evaluated, of which 77 had a mutation and 23 had a previous cancer diagnosis. The mean age of family members evaluated for BRCA2 mutation was 43 years, similar to the mean age at diagnosis of the proband: 41 years. The NM_000059.4:c.1389_1390del and NM_000059.4:c.7124T > G variants was the most frequent in BRCA2. Conclusions: This data reinforces the importance of genetic counseling and testing of family members when a pathogenic variant is identified in a cancer patient. It is clear that early initiation of surveillance protocols, with screening and prophylactic surgeries are very effective tools for those high risk patients, they just have to be early diagnosed with the PV to benefit from this strategies. In addition, this assessment helps in understanding the mutational profile of the population in order to improve the planning of services in oncogenetics.