Background: Response to neoadjuvant chemotherapy (NAC) for breast cancer varies by tumor characteristics and therapy regimen. Studies suggest that patient ethnicity is associated with differences in disease presentation, response to treatment, and outcomes. There exists a paucity of literature on the presentation and outcomes of NAC for breast cancer in Hispanic women. Methods: This is an IRB-approved retrospective study of breast cancer patients who underwent NAC at an NCI-designated Comprehensive Cancer Center from 2005-2020. We reviewed demographics, disease presentation, response to treatment, and outcomes. ER and PR status were categorized as low positive (1-9%), positive (≥ 10%) and negative. Treatment factors reviewed included completion of chemotherapy and type of surgery performed. Treatment response was noted as percent residual cellularity (0%, <10%, 10-30%, >30-80% and >80%) in the surgical specimen and pathologic stage. Outcomes were assessed as overall survival (OS) and recurrence. Results: 365 patients received neoadjuvant chemotherapy from 2005-2020, and 196 (53.7%) self-identified as Hispanic. Median follow-up was 13.65 years. Highest clinical stage at diagnosis was most frequently IIA (31.2%), followed by IIB (32.3%), with non-significant Hispanic ethnicity differences, although Hispanic patients presented with higher clinical prognostic stages: IIIA or higher (40.5% vs. 24.0%). Hispanics more frequently had grade 3 tumors (60% vs. 48%), ER low positive (10% vs. 7%) and ER negative (48% vs. 36%) (p=0.02). No significant differences were noted in triple negative disease or HER2 positive disease. Hispanics were diagnosed at younger average ages (48.9 vs. 53.0 years, p=0.001). No statistically significant differences were noted in time from diagnosis to NAC initiation, completion of chemotherapy, or surgical treatment received (lumpectomy vs. mastectomy, and sentinel node biopsy vs. dissection). Mastectomy was more likely for late-stage disease (OR=2.73, 95% CI: 1.66-4.49, p<0.001); Hispanic women with late-stage disease had 1.09-fold higher odds of receiving mastectomy, but this was non-significant (95% CI: 0.66-1.79). No significant ethnic differences were noted in pCR (p=0.69) or residual tumor cellularity (p=0.63). There was no significant association between residual cellularity and OS. OS rates were similar for Hispanic vs. Non-Hispanic women (HR: 1.15, 95% CI: 0.64-2.08, p=0.63). No difference was noted in ethnicity-based recurrence rates (21.4 vs. 20.1%). Conclusion: Self-identified Hispanic patients were diagnosed at a younger age, presented with higher ER negative and low-positive disease and worse prognostic clinical stage. However, given standard of care chemotherapy, there were no significant differences in their treatment response or outcomes compared to non-Hispanic patients. Citation Format: Sangeetha Prabhakaran, Christopher McNicoll, Vernon S. Pankratz, Nadja Falk, Jacklyn Nemunaitis, Jain Zhou, Payton A. Sandoval-Belt. Differences in disease presentation, and treatment outcomes of neoadjuvant chemotherapy for breast cancer among Hispanics in a minority-serving institution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3686.

Background: Response to neoadjuvant chemotherapy (NAC) is an indicator of outcomes and can be quantified as achievement of pathologic complete response (pCR) (absence of residual invasive disease in breast and lymph nodes) and residual percent cellularity. However, the significance of residual tumor cellularity post-NAC is not well understood. We assessed the impact of NAC-induced reduction in tumor cellularity among hormone receptor subtypes and the effect of these reductions on overall survival (OS). Methods: An IRB-approved retrospective review identified demographics, disease presentation, response to treatment, and outcomes. ER and PR status were categorized as low positive (1-9%), positive (≥ 10%) and negative. Treatment response was noted as percent residual cellularity (complete 0%, almost complete < 10%, good 10-30%, moderate >30-80% and poor >80%) in the surgical specimen and pathologic stage. We examined measures of response to NAC within breast tumor subtypes and the effect of these responses on associations with OS among hormone receptor subtypes. Results: The clinical series comprised 384 patients who received curative intent NAC. This series was diverse in presentation, displayed considerable variability in response to NAC (Table 1). 88 (23.6%) patients did not experience tumor down staging, and of those presenting with clinical nodal Stage 1 or higher (n=197), 94 (47.7%) did not experience nodal down staging. Although Triple Negative Breast Cancer (TNBC) status was not significantly associated with post-NAC residual tumor cellularity (p=0.74), ER, PR, and HER2 status were individually associated with this measure of response to NAC (p=0.04, 0.01, and 0.01, respectively). However, none of these associations explained more than 2.5% of the variability in this marker of treatment response. Median non-censored follow-up time was 4.26 years. Accounting for censoring, median survival was 13.65 years (lower 95% confidence limit was 11.79 years). Differential associations with OS were observed for three hormone receptor subtypes (ER: p< 0.001, HER2: p=0.04, and TNBC: p< 0.001) according to residual tumor cellularity, classified by percent residual cellularity categories of complete or almost complete response versus all others. Importantly, although ER negative patients with poor residual cellularity response had worse OS than ER positive patients with good response (Hazard Ratio [HR], 95% Confidence Interval [CI] = 4.74, 2.2-10.2), ER negative patients with good response did not have significantly worse OS than ER positive patients with good response (HR, 95% CI = 1.37, 0.57-3.26). Similar patterns were seen for patients with HER2 negative breast cancer or TNBC. Chemo resistant TNBC patients had higher risks for mortality than if they were not chemo resistant (HR, 95% CI: 2.41, 1.02-5.71). Conclusions: Our data suggest that OS associated with different hormone subtypes differs according to response to NAC. Differential OS according to response to NAC is greatest for patients classified according to ER status influences, with good response eliminating much of the differential mortality risk between ER negative and positive patients. There is a similar difference according to TNBC, although the difference appears to be less complete. Further studies should focus on understanding the chemo resistance of ER negative tumors, and perhaps TNBC, to identify mechanisms that may ultimately drive treatment response and survival. Table 1. Demographic and other characteristics Citation Format: Sangeetha Prabhakaran, V. Shane Pankratz, Christopher McNicoll, Nadja Falk, Jacklyn Nemunaitis, Jain Zhou, Payton Sandoval-Belt. Breast cancer patients with different hormone receptor subtypes receiving neoadjuvant chemotherapy (NAC) experience differential overall survival according to their resistance to NAC [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-15.