Racial and ethnic differences in response to neoadjuvant chemotherapy and the impact on overall survival among early-stage ERBB2-low breast cancer patients

Abstract Background: Recent studies have reported a pathologic complete response (pCR) rate of 13.0-36.3% in patients (pts) with early-stage human epidermal growth factor receptor-2 (ERBB2 [formerly HER2])-low breast cancer after neoadjuvant chemotherapy (NACT), however, have found contradicting results comparing survival outcomes between pts with ERBB2-low and pts with ERBB2-0 tumors. Further, racial/ethnic differences in pCR, and in overall survival (OS) by pCR status, among early-stage ERBB2-low breast cancer pts after NACT are unknown. Methods: We analyzed data from early-stage ERBB2-low breast cancer pts in the 2010-2020 National Cancer Database, a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. Racial/ethnic groups included Asian/Pacific Islander (API), American Indian/Alaska Native (AIAN), Black, Hispanic, and White. ERBB2-low was defined as having an IHC score of 1+ or 2+, without gene amplification by FISH. pCR (ypT0/Tis ypN0) status was dichotomized as “achieved/did not achieve,” modeled using multivariable logistic regression. OS, measured from the surgery date to the date of death or the last contact, was modeled using multivariable Cox proportional hazard regression by pCR status. Results: Of 25,577 pts (mean age 54 years [SD=12]), most (66.0%) were White, followed by 18.0% Black, 9.1% Hispanic, 5.1% API, and 1.8% AIAN. Overall, 15.2% achieved pCR. Black pts achieved a 17.4% pCR rate, Hispanic 16.0%, White 14.7%, API 13.5%, and AIAN 10.9%. After adjusting for clinicopathological characteristics, AIAN pts had lower odds of pCR achievement than White pts (adjusted odds ratio [AOR]=0.66, 95% CI: 0.48-0.91). There were no statistically significant differences in the odds of pCR achievement between Hispanic and White pts (AOR=1.12, 95% CI: 0.98-1.29), between Black and White pts (AOR=1.01, 95% CI: 0.92-1.12), or between API and White pts (AOR=0.95, 95% CI: 0.79-1.14). Among pts who did not achieve pCR, API (adjusted hazard ratio [aHR]=0.62; 95% CI: 0.51-0.76) and Hispanic (aHR=0.77, 95% CI: 0.67-0.89) pts had a significantly lower risk of death than White pts; mortality risk was marginally statistically significant comparing Black with White pts (aHR=1.07, 95% CI:1.00-1.17) and was not statistically significant comparing AIAN with White pts (aHR=0.88, 95% CI: 0.65-1.18). Among pts who achieved pCR, we did not observe statistically significant differences in the risk of death between Hispanic and White pts (aHR=1.08, 95% CI: 0.66-1.78), between Black and White pts (aHR=0.77, 95% CI: 0.55-1.09), between API and White pts (aHR=0.41, 95% CI: 0.15-1.12), or between AIAN and White pts (aHR=0.35, 95% CI: 0.05-2.50). Conclusions: In this large national cohort of pts with early-stage ERBB2-low breast cancer, post-NACT pCR was highest in Black and lowest in AIAN pts. Compared with White pts, only AIAN pts showed significantly lower odds of achieving pCR. Our findings suggest further investigation of possible causes of racial/ethnic OS differences after NACT in this patient population. Citation Format: Jincong Q. Freeman, James L. Li, Olasubomi Omoleye. Racial and ethnic differences in response to neoadjuvant chemotherapy and the impact on overall survival among early-stage ERBB2-low breast cancer patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B010.