Abstract PS3-02-10: Pathologic Complete Response in Germline Pathogenic Variant Carriers: a Comparison Study Between a Safety-Net and Academic Population

Abstract Background: Pathologic complete response (pCR) after neoadjuvant chemotherapy in breast cancer (BC) has important prognostic implications. Understanding its associations with pathogenic/likely pathogenic variants (P/LPV) in hereditary cancer genes (HCG) adds further prognostic value. Minorities remain underrepresented in hereditary cancer research. In this retrospective chart review, we compare pCR rates among patients with P/LPV in HCG at a safety-net clinic comprised of majority Latino patients to those at an academic clinic with majority white patients. Methods: All patients at Baylor St. Luke's Medical Center (BSLMC, academic clinic) and Smith Clinic (SC, safety-net clinic) with a diagnosis of stage I-III BC who were found to have a P/LPV in HCG from 10/1/09-9/30/19 and received neoadjuvant chemotherapy followed by surgery were included. Demographic, clinical characteristics, and pathologic data were collected. Results: 118 patients qualified for analysis (71 from SC, 47 from BSLMC). In SC 50 (70%) were Latino, 3 (4.2%) White, 11 (15.5%) Black, and 1 (1.4%) Asian. In BSLMC, 15 (32%) were Latino, 20 (42.6%) White, 8 (17%) Black, and 2 (4.3%) Asian. Median age was 42 for SC and 54 for BSLMC. SC comprised of 41 (58%) BRCA1+, 13 (18.3%) BRCA2+, and 12 (16.9%) PALB2+ patients. BSLMC comprised of 16 (34%) BRCA1+, 8 (17%) BRCA2+, 6 (12.8%) ATM+, 5 (10.6%) CHEK2, and 3 (6.4%) PALB2+. SC and BSLMC patients ranged from stage I-III, with 49% and 36.2% falling in stage III respectively. SC had 37 (52.1%) triple negative BC (TNBC) patients, 25 (35.2%) ER/PR+, HER2- (HR+), 7 (9.9%) ER+/HER2+, and 2 (2.8%) ER-/HER2+. BSLMC had 14 (29.8%) TNBC, 25 (53.2%) HR+, 7 (14.9%) ER+/HER2+, and 1 (2.1%) ER-/HER2+. 36 (51%) and 21 (44.7%) were treated with both anthracycline and taxanes in the SC and BSLMC populations respectively.In the SC population, pCR rates (detailed in Table 1) were highest among TNBC (16, 43.2%). Of the TNBC patients that had pCR, 15 (94%) had P/LPV in a high-risk HCG (BRCA1/2 or PALB2). Similarly, of the HR+ patients that had pCR, 6 (85%) had P/LPV in a high-risk HCG. In the BSLMC population, pCR was achieved in 4 (28.6%) TNBC patients. Of these patients, 4 (100%) carried P/LPV in a high-risk HCG. Of the HR+ patients that had pCR, 4 (80%) had P/LPV in a high-risk HCG. RCB class by hereditary P/LPV and biomarker status will be reported. Conclusions: Rates of P/LPV in high-risk HCG (BRCA 1/2 and PALB2) were higher in the SC population compared to BSLMC, which may be reflective of differences in ethnicities. Across both institutions, pCR rates were highest among patients with high-risk P/LPV, detailed in Table 1. When further divided by biomarker, HR+ patients had relatively high pCR rates. More data in patients with P/LPV in HCG may help us better determine prognosis and optimize treatment strategies. Given the high pCR rate in high-risk HCG, consider germline genetic testing in HR+ BC patients with pCR. Citation Format: E. Low, N. Nyamongo, A. Lackan, C. Gonzalez, K. Hoffman, N. Kunta, S. Sarlin, S. Bulsara, S. Hilsenbeck, T. Snow, C. Sullivan, G. Garza, A. Elkhanany, N. Chen, K. Osborne, M. F. Rimawi, S. Shah, J. Nangia. Pathologic Complete Response in Germline Pathogenic Variant Carriers: a Comparison Study Between a Safety-Net and Academic Population [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-02-10.