Multi‐gene panel analysis in BRCA1/2‐negative patients suspected of hereditary breast and ovarian cancer syndrome: Real‐world data from a single institution

Abstract Aim Although BRCA1/2 is most frequently associated with hereditary breast and ovarian cancer (HBOC), many other related genes have been implicated. Therefore, we investigated the prevalence of non‐ BRCA1/2 genes associated with hereditary cancer predisposition in BRCA1 /2‐negative patients from the Department of Genetic Medicine and Services with breast and ovarian cancer using a multi‐gene panel (MGP) analysis. Methods We conducted a retrospective MGP analysis (National Cancer Center Onco‐Panel for Familial Cancer; NOP_FC) in BRCA1/2 ‐negative patients with breast, ovarian, and overlapping breast/ovarian cancers who visited our genetic counseling between April 2004 and October 2022. Results NOP_FC was performed in 128 of the 390 BRCA test‐negative cases (117 breast cancer, 9 ovarian cancer, and 2 overlapping breast/ovarian cancer cases). Among the BRCA1/2 ‐negative patients, nine (7.7%) with breast cancer and one (11%) with ovarian cancer had pathogenic variants (PVs) in non‐ BRCA1/2 genes associated with breast and ovarian cancers, respectively. Five patients had PVs in RAD51D , two in PALB2 , one in BARD1 , one in ATM , and one in RAD51C . Conclusions Additional MGP testing of germline genes associated with hereditary cancer predisposition syndrome in BRCA1/2 ‐negative breast and ovarian cancer patients revealed PVs in non‐ BRCA1/2 breast cancer‐ and ovarian cancer‐related genes in 7.7% of breast cancer and 11% of ovarian cancer. Therefore, additional testing may provide useful information for subsequent risk‐reducing surgery and surveillance in BRCA1/2 ‐negative patients.