LAUSR

Abstract Background Biliary tract cancers (BTCs) are rare. They are clinically and pathologically heterogeneous and associated with a poor prognosis. BRCA 1/2 are tumor suppressor genes responsible for a high number of hereditary breast and ovarian cancers. BRCA2 mutations are also associated with higher risk of other cancers, including prostate and pancreatic cancers. BTC-associated with BRCA mutation is still unclear. In this study, we analyzed the frequency and characteristics of BTCs in confirmed BRCA Portuguese families. Methods Retrospective analysis of all BRCA1/2 families registered in our multidisciplinary program since January 2000 was performed. All cases of BTCs, on the mutated side of the family were included. Results From 513 BRCA1/2 families, 187 were BRCA1 and 325 BRCA2. BRCA2 c.156_157insAlu - the Portuguese founder mutation - was observed in 101 families. We identified BTCs in seven BRCA2 families, five of which were c.1567_157insAlu. Overall, 7 cases of BTCs were identified (5 with pathological confirmation): 5 BRCA2 carriers and 2 first-degree relatives of BRCA2 carriers. Median age at diagnosis was 63 years, with male and female prevalence rates of 57% and 43%, respectively. Two cases of BTC were diagnosed in two female survivors of breast cancer. One female survivor of BT developed peritoneal carcinoma after prophylactic salpingo-oophorectomy. All BRCA2 families revealed a heterogeneous phenotype: 5 out of 7 families have aggregation to pancreatic and/or stomach cancers. Four patients died, three from BTC disease progression and one from peritoneal carcinoma. The other 3 patients are alive without relapse. Conclusions BRCA-associated BTCs are uncommon. Surveillance and prophylactic surgery reduces the risk of death from breast and ovarian cancer in BRCA2 carries allowing the diagnosis of other type of cancer during the follow-up, such as BTCs. Therefore, it is crucial the development of surveillance protocols for gastrointestinal tumours. Diagnosis of BTC-associated germline BRCA mutations might have clinical implications, expanding roles in treatment planning and allowing application of targeted therapies. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.