AbstractBackgroundBreast cancer (BC) with germline BRCA1/2 mutations and their association with triple‐negative BC has been thoroughly investigated. However, some carriers of BRCA1/2 mutations have human epidermal growth factor receptor 2 (HER2/neu)‐positive BC, which has a different targeted therapy approach, and data are scarce for this patient population. The authors sought to characterize the clinical characteristics and outcomes of patients with HER2/neu‐positive BC who had germline BRCA1/2 mutations.MethodsThis was a retrospective analysis of data from 1099 patients diagnosed with HER2/neu‐positive BC who were screened for germline BRCA mutations between 1996 and 2022. Clinicopathologic features and survival rates were analyzed by BRCA mutation status. Univariate and multivariable Cox proportional hazards regression models were used to analyze the association between clinical variables and outcomes.ResultsOf 1099 patients with HER2/neu‐positive BC, 73 (6.6%) tested positive for BRCA1/2 mutations. Age, race, and tumor characteristics did not differ between BRCA noncarriers and carriers. At a median follow‐up of 78.6 months, the 5‐year recurrence‐free survival rate was 85% in BRCA carriers and 87% in noncarriers (p = .79), and the 5‐year overall survival rate was 94% in BRCA carriers and 94% in noncarriers (p = .78). In a multivariable model, BRCA was not associated with recurrence‐free survival (hazard ratio, 0.99; 95% confidence interval, 0.51–1.90; p = .96) or overall survival (hazard ratio, 0.83; 95% confidence interval, 0.33–2.07; p = .69).ConclusionsBRCA1/2 mutations occurred in 6.6% of patients with HER2/neu‐positive BC and did not affect survival outcomes. Assessing the potential benefits of new treatment strategies, such as combining anti‐HER2/neu therapies with poly(ADP‐ribose) polymerase inhibitors, may lead to enhanced outcomes for these patients.