Pathologic complete response and association with survival benefit in hormone receptor–positive breast cancer BRCA carriers.

e12670 Background: In hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2–) breast cancer, the prognostic significance of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) is less consistent than in triple-negative or HER2-positive disease. BRCA1/2 pathogenic variant carriers demonstrate higher pCR rates to chemotherapy, even within HR+/HER2– tumors, suggesting potential differential chemosensitivity. We evaluated the association between pCR and long-term outcomes among BRCA carriers with HR+/HER2– breast cancer. Methods: We conducted a retrospective, single-institution cohort study of consecutive BRCA1/2 pathogenic variant carriers diagnosed between January 2000 and December 2024. Patients with HR+ (ER > 1%), HER2– stage I–III breast cancer who received NAC were included. The primary endpoint was pCR rate. Secondary endpoints included distant recurrence-free survival (DRFS) and locoregional recurrence. Survival outcomes were estimated using the Kaplan–Meier method and compared using the log-rank test. Results: Among 579 BRCA carriers with stage I–III breast cancer, 169 had HR+/HER2– disease; 49 received NAC and comprised the study cohort. Median age was 39.8 years (range, 24–61), and 27 patients (55%) had BRCA2 mutations. Most received anthracycline- and taxane-based NAC;3 received anthracycline-only NAC, followed by adjuvant a taxane-based therapy. Adjuvant systemic therapy included endocrine therapy in 43/49 patients, olaparib in 14 patients, and abemaciclib in five patients. Median follow-up time was 56.9 (range 7-193) months. The overall pCR rate was 22.4% (11/49), including 31.8% (7/22) among BRCA1 carriers and 14.8% (4/27) among BRCA2 carriers (Fisher’s exact p = 0.185). Among patients achieving pCR, one contralateral breast cancer event occurred, with no distant recurrences observed. In contrast, among patients without pCR, 13 of 38 (34.2%) developed distant recurrence, including one with synchronous local recurrence. Metastatic recurrence occurred in 2 of 12 patients (16.7%) with residual stage I disease compared with 11 of 26 patients (42.3%) with residual stage II–III disease. Ten deaths occurred during follow-up, nine attributable to metastatic breast cancer. Five-year DRFS was 100% in patients achieving pCR versus 61.9% in those without pCR (log-rank p = 0.037). Conclusions: Among BRCA carriers with HR+/HER2– breast cancer treated with NAC, pCR was associated with significantly improved distant recurrence-free survival whereas patients with residual disease—particularly those with residual stage II–III tumors—experienced a high risk of distant recurrence. These findings support pCR as a meaningful prognostic marker in this biologically distinct population and highlight the need for post-neoadjuvant risk-adapted strategies for patients with residual disease after NAC.