BRCA1/2 Carriers With Breast‐Ovarian Double Primary Cancers Versus Ovarian Cancer Alone: Mutation Profiles and Survival Outcomes

ABSTRACT Germline pathogenic variants in BRCA1/2 substantially increase lifetime risks of both breast and ovarian cancers. However, whether specific mutation characteristics predispose carriers to breast‐ovarian double primary cancers (DPC) and whether DPC affects ovarian cancer outcomes—particularly in the PARP inhibitor (PARPi) era—remain unclear. We conducted a retrospective analysis of patients with germline BRCA1/2 ‐mutated high‐grade serous ovarian cancer in China from 2015 to 2025, including 114 DPC patients and 296 ovarian cancer (OC)‐only patients as controls. Clinical characteristics, mutation profiles, and survival outcomes were compared between the two groups. Among 114 DPC patients, 92 were diagnosed with breast cancer first, 12 with ovarian cancer first, 9 had synchronous diagnoses, and 1 was unknown. Compared with the OC‐only group, BRCA1/2 mutations in the DPC group were predominantly located outside the Ovarian Cancer Cluster Region ( BRCA1 : 63.1% vs. 48.9%, p  = 0.019; BRCA2 : 80.0% vs. 56.2%, p  = 0.008). Among BRCA2 ‐mutated patients, DNA‐binding domain mutations were enriched in the DPC group (33.3% vs. 17.8%, p  = 0.018). Both groups benefited from first‐line PARPi maintenance. No significant differences in progression‐free or overall survival were observed between DPC and OC‐only patients on either univariable or multivariable analysis. A subgroup analysis restricted to the 92 patients whose breast cancer preceded ovarian cancer yielded consistent results. In conclusion, the location of BRCA1/2 mutations influences susceptibility to breast‐ovarian DPC. DPC status was not significantly associated with inferior survival in this cohort; however, long‐term outcomes warrant validation in larger, prospectively followed populations.