Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
Maria Beatriz Mira , Isalia Margarida Campos Miguel , Sofia Fragoso , Ana Luís , Ana Clara , Sandra Bento , Ana Gaspar Opiniao , Patricia Machado , Sidonia Santos , Paula Rodrigues , Joana Parreira , Ana Francisca , Fatima H. Vaz
Background: Germline mutations impacting homologous recombination repair have been associated with predisposition to breast (BC) and ovarian cancer (OC). OC, even if no family history (FH) confers a 10% combined probability of BRCA1/2 mutations, being a criteria for testing. BRCA1/2 detection rate may vary FH and pathology. Besides BRCA1/2, other genes have also been associated with hereditary OC. Methods: all index, consecutive, OC patients (pts) counselled between September 2016-December 2017 were tested upfront for a panel testing (PT) including BRCA1, BRCA2, RAD50, RAD51C, RAD51D and BRIP1 (BRCA Hereditary Cancer MASTER Plus methodology). All pts were required to have a pathology confirmation of OC (mucinous cases excluded). In here, we analyze the molecular results and discuss the clinical potential of PT for OC. Results: 109 female pts consented to PT (108 OC pts and 1 BC pt with a first degree relative with OC). Medium age at testing was 58.1 years (26-83). Pathogenic variants were found in 20 pts (18.3%): BRCA2– 8 (40%), BRCA1– 5 (25%), RAD51C– 3 (15%), RAD51D– 2 (10%), RAD50– 1 (5%), BRIP1– 1 (5%). Of the 8 BRCA2 pts, 2 were diagnosed with the c.156_157insAlu mutation. 13 pts (65%) had high grade serous OC and 4 pts endometrioid OC (20%). 2 pts had low grade OC, both stage III at diagnosis – one with a RAD51C mutation (c.404G > A, p.C135Y) and other with a pathogenic BRCA2 variant (c.156_157insAlu). All of these pts (except the one with BRIP1 mutation) had a personal history of OC and 3 of them had had BC and OC (1 BRCA1, 2 BRCA2). The pt with the BRIP1 mutation (c.484C > T; p.Arg162Ter) was the only one without OC: she was as BC survivor with a FH of OC. Conclusions: With this panel, and without restrictions relating to non-mucinous pathology, we observed a high (18%) germline mutation detection rate for OC. Adding 4 genes to BRCA1/2 testing increased the mutation detection rate by 53.8%. Even if counselling is complex in families harbouring variants in moderate penetrance genes, our results suggest clinical utility for OC prevention. Other genes will be included in our upfront OC panel.
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