Response to Treatment, Racial and Ethnic Disparity, and Survival in Patients With Breast Cancer Undergoing Neoadjuvant Chemotherapy in the US

Abstract

Importance: With the increasing delivery of neoadjuvant chemotherapy (NACT) for patients with breast cancer in the US, it is important to know whether there is differential response to NACT by race and ethnicity and the potential long-term outcomes.

Objective: To examine whether there were any racial and ethnic differences in pathologic complete response (pCR) rate following NACT and, if so, whether they varied by molecular subtype and were associated with survival.

Design, setting, and participants: A retrospective cohort study was conducted including patients with stage I to III breast cancer diagnosed between January 2010 and December 2017 who underwent surgery and received NACT; median follow-up was 5.8 years, and data analysis was conducted from August 2021 to January 2023. Data were obtained from the National Cancer Data Base, a nationwide, facility-based, oncology data set that captures approximately 70% of all newly diagnosed cases of breast cancer in the US.

Main outcomes and measures: Pathologic complete response, defined as ypT0/Tis ypN0, was modeled using logistic regression. Racial and ethnic differences in survival were analyzed using a Weibull accelerated failure time model. Mediation analysis was conducted to measure whether racial and ethnic differences in the pCR rate affect survival.

Results: The study included 107 207 patients (106 587 [99.4%] women), with a mean (SD) age of 53.4 (12.1) years. A total of 5009 patients were Asian or Pacific Islander, 18 417 were non-Hispanic Black, 9724 were Hispanic, and 74 057 were non-Hispanic White. There were significant racial and ethnic differences in pCR rates, but the differences were subtype-specific. In hormone receptor-negative (HR-)/erb-b2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-positive (ERBB2+) subtype, Asian and Pacific Islander patients achieved the highest pCR rate (56.8%), followed by Hispanic (55.2%) and non-Hispanic White (52.3%) patients with the lowest pCR rate seen in Black patients (44.8%). In triple-negative breast cancer, Black patients had a lower pCR rate (27.3%) than other racial and ethnic groups (all >30%). In HR+/ERBB2- subtype, Black patients had a higher pCR rate (11.3%) than other racial/ethnic groups (all ≤10%). In mediation analysis, racial and ethnic differences in achieving pCR after NACT could explain approximately 20% to 53% of the subtype-specific survival differences across racial and ethnic groups.

Conclusions and relevance: In this cohort study of patients with breast cancer receiving NACT, Black patients had a lower pCR rate for triple-negative and HR-/ERBB2+ breast cancer but a higher pCR rate for HR+/ERBB2- diseases, whereas Asian and Pacific Islander patients had a higher pCR rate for HR-/ERBB2+ diseases. Tumor grade and ERBB2 copy number could account for some of these within-subtype disparities, but further studies are warranted. Inability to achieve a pCR can mediate in part, but not entirely, the worse survival outcomes experienced by Black patients.

Figure 1.. Distribution of Erb-b2 Receptor Tyrosine Kinase 2 (ERBB2)/CEP17 Ratio by Race and Ethnicity in Patients With ERBB2-Positive (ERBB2+) Breast Cancer

In the hormone receptor–positive (HR+)/ERBB2+ subtype (A), the median ERBB2/CEP17 ratio was 3.3 for Asian and Pacific Islander, 3.3 for Black, 3.2 for Hispanic, and 3.3 for White patients. In the hormone receptor–negative (HR−)/ERBB2+ subtype (B), the median ERBB2/CEP17 ratio was 4.9 for Asian and Pacific Islander, 3.5 for Black, 4.5 for Hispanic, and 4.1 for White patients.

Figure 2.. Overall Survival by Race and Ethnicity and Response Status in 4 Molecular Subtypes

ERBB2 indicates erb-b2 receptor tyrosine kinase 2; HR, hormone receptor; −, negative; pCR, pathologic complete response (solid lines); +, positive; RD, residual disease (dashed lines); and TNBC, triple-negative breast cancer.