Racial Disparity in Tumor Microenvironment and Outcomes in Residual Breast Cancer after Neoadjuvant Chemotherapy

Abstract

Black patients with residual estrogen receptor-positive (ER+) breast cancer after neoadjuvant chemotherapy (NAC) have inferior survival compared to white women resulting racial disparity in breast cancer survival. Differences in the tumor microenvironment (TME) might be one of the mechanisms behind the racial disparity in outcome. The hypothesis of this thesis study is “Racial disparity in Distant Recurrence-Free Survival (DRFS) in patients with residual ER+/ Human Epidermal Growth Factor Receptor 2 negative (HER2-) disease is due to enhanced pro-metastatic components (macrophage, microvasculature, cancer stem cell, and Tumor Microenvironment of Metastasis (TMEM) doorway density) in the tumor microenvironment post-NAC”. We stained 183 invasive ductal carcinoma tissue samples (96 Black women, 87 white women) for TMEM doorways (Pan-Mena expressing tumor cell, CD68 macrophages, and CD31 endothelial cells) and SOX9 expressing cancer stem cells (CSCs). TMEM doorway score and macrophage density were more in Black patients in the entire cohort and in the ER+/HER2- disease. TMEM doorway was an independent prognostic factor overall. There was no racial disparity in microvascular density and CSCs. In conclusion, high-TMEM doorway score was an independent prognostic factor of worse survival in patients with residual cancer post-NAC. Racial disparity in outcome might be due to an increased pro-metastatic response to chemotherapy in Black relative to white patients with residual ER+/HER2- disease.