Prevalence study of BRCA1/2 mutations in Portuguese patients diagnosed with non-mucinous ovarian cancer, fallopian tube invasive neoplasia or peritoneal primary cancer (PADOC)

Objectives: Family history is a representative risk factor for ovary cancer (OC), frequently associated with BRCA1/2 mutations. The primary objective was to determine the prevalence of BRCA1/2 mutations (somatic and germline) in patients with non-mucinous ovarian cancer (NMOC), invasive fallopian tube neoplasia (IFTN) or primary peritoneal carcinoma (PPC). Methods: National, interventional, retrospective and analytical study, with an estimated sample size of 261 women aged ≥18 years, diagnosed with NMOC, IFTN or PPC between 01/01/2014 and 31/12/2016 in the nine selected centers. Results: From 165 women eligible for analysis, the prevalence of BRCA1/2 mutation was 20% (24.2% somatic, 75.8% germline). For patients with a mutation, 54.5% had a mutation in BRCA1 (27.8% somatic, 72.2% germline), while 45.5% in BRCA2 (20.0% somatic, 80.0% germline). Mean age of the sample was 61.1 years (mutated 60.3 years, non-mutated 61.3 years For patients with a mutation, the ages of the subgroups with somatic and germline were 70.5 and 57.0 years, respectively, with statistically significant difference. Furthermore, patients with somatic mutation were 68.1 years at diagnosis, whereas those with germline were 54.6 years, with statistically significant difference. In addition, 56.4% of patients with a mutation had disease in stage III and 18.8% in stage IV. Regarding family history, 20.6% of the total had confirmed family history of BRCA associated cancer, being that information unknown by 29.1%. In patients with BRCA1/2 germline mutation, 48.0% confirmed family history of BRCA-associated tumors, in opposition to 15.2% in the non-mutated group. From the patients with mutation who reported familial history, 75.0% reported breast cancer, 33.3% ovarian cancer and 15.0% other tumors. Conclusions: PADOC study evaluated for the first time the nationwide prevalence of BRCA1/2 germline and somatic mutations in ovarian cancer in Portugal, and the results suggest an estimated prevalence of 20.0%. These results highlight the importance of raising awareness for the disease in Portugal and the recommendation of broad genetic testing also bearing in mind the percentage of patients that have no information of BRCA-related cancers in family.