Racial Difference in Outcomes in Breast Cancer Patients with Residual Nodal Disease after Neoadjuvant Chemotherapy

Abstract

African Americans (AA) requiring neoadjuvant chemotherapy (NAC) have been associated with worse outcomes. Residual nodal disease (ypN+) after NAC represents a highly unfavorable risk factor. We hypothesized that even within this unfavorable subgroup, that racial differences in outcome would persist. An IRB-approved retrospective review of breast cancer (BC) patients in a multi-institutional study was performed between 2005-2018 to identify ypN+ patients (excluding metastatic or inflammatory BC). Clinico-pathologic parameters stratified by race were collected and analyzed. For molecular subtype analyses, patients were stratified into triple negative (TN), hormone receptor (HR)+/HER2-, and HR+/HER2+, and HR-/HER2+ subtypes. Overall survival (OS), disease free survival (DFS) and recurrence outcomes were obtained, and univariate and multivariate (MVA) logistic regression models were constructed and analyzed. Among 404 ypN+ patients, 107 (26%) were AA, and 297 (74%) were non-AA. Median follow-up for the non-AA group was 3.8 years (y) (IQR 2.4-6.3) and 3.5y (IQR 2.0-6.2) for the AA group. Clinical and pathologic patient characteristics (age, molecular subtypes, BRCA status, histology, grade, smoking status, primary surgery type, axillary/reconstruction surgery rates, margin status, stage) were without significant statistical differences between the non-AA and AA group, except the non-AA group had proportionally more cN3 disease (10.5% vs. 5.1%; p = .01). Despite this, AA demonstrated worse OS and DFS outcomes (Table). AA also had significantly worse local (15% vs. 6.7%, p = .02), regional (11.2% vs. 5.1%, p = .05) and distant recurrences (32.7% vs. 22.6%, p = .05) compared to non-AA. On MVA for OS and DFS, HR+ status, clinical stage, and AA race (HR 2.1 (CI 1.3-3.4), p = .004 and HR 1.7 (CI 1.1-2.6), p = .01 respectively) remained significant. Molecular subtype analysis demonstrated that AA with HR+/HER2- but not the TN subtypes demonstrated significantly worse outcomes (Table). Utilization of endocrine therapy was not different between AA and non-AA patients (94% vs. 97%, p = 0.3) to explain this discrepancy. Worse outcomes in HER2 subtype for AA group was suggested but could not be statistically verified due to insufficient sample size. There was no discernible difference in chemotherapy and radiation therapy regimen or compliance between the AA and non-AA groups. AA patients who fail to achieve nodal clearance with NAC had higher local, regional and distant recurrence, and worse survival compared to non-AA, particularly those with non-TN status. These differences could not be readily explained by therapeutic disparity, or compliance. These hypothesis generating findings suggest need to explore biological implications, and alternative therapeutic strategies for this unfavorable subgroup.