Germline mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2 are associated with inherited predisposition for breast and ovarian cancer. Pattern of mutations varies considerably among different populations, and there are groups with high prevalence of particular mutations according to geographical area, as the c.156_157insAlu BRCA2 rearrangement, a founder mutation of Portuguese origin and one of the most frequent BRCA2 mutations described to date. In this study we review the clinical and pathological characteristics of the patients with Hereditary Breast and Ovarian Cancer Syndrome (HBOC), the BRCA1 and BRCA2 mutation spectrum and evaluate its relation with clinical outcomes.
Retrospective analysis of families with HBOC of our clinic between January 2007 and December 2017. Myriad or BRCAPRO model was applied and individuals with score ≥ 10% were tested for BRCA1/2 mutations, using PCR sequencing and MLPA technique. Data was analyzed with SPSS statistics software.
Ninety-four families with 378 members were evaluated. BRCA1 mutation was identified in 182 individuals, and BRCA2 in 111 individuals. In BRCA1 population, 42 individuals (40 females, 2 males) with cancer (affected individuals – AI) were identified, mainly with triple-negative breast cancer (BC) (57%). The most frequently detected mutations were exon 16_17del, c.1121_1123delCACinsT and c.2037delGinsCC which together represented 31% of total pathogenic mutations. In BRCA2 population, 62 AI were identified (55 females, 6 males), mainly with luminal BC (71.4%). The c.156_157insAlu BRCA2 rearrangement represented 61% of total pathogenic mutations. Rate of risk reducing surgeries was similar in both groups. Five-year overall survival was 82.5% in BRCA1 AI vs 86.4% in BRCA2 AI.
Our results are consistent with literature in terms of genotype-phenotype relation and frequency of founder mutations. Identify the most frequent mutations in each population is crucial for a personalized approach of patients and to define strategies of surveillance for patients and relatives at risk. Prognostic impact of these mutations in outcomes in BC has not been fully determined to date. Further studies including this population are warranted.
Susana Amaral.
Has not received any funding.
All authors have declared no conflicts of interest.