Strong Tumor Expression of ALDH1A1 is Associated with Black Race, Metabolic Disorders, and Poor Breast Cancer Outcomes

Abstract

Racial differences in tumor biology may explain worse breast cancer outcomes in Black women relative to White women. This study provides a comparative racial analysis in Black and White women in terms of Aldehyde dehydrogenase 1 member A1 (ALDH1A1) expression and its association to clinicopathological features. Expression of ALDH1A1 in both tumor and stromal cells was assessed by immunohistochemistry in tissue microarrays containing 253 breast tumors including 161 tumors from White patients and 92 from Black patients. Relationships to clinicopathological features for strong and moderate to low ALDH1A1 staining were determined using Pearson’s Chi Square and an odds ratio was determined. Survival and recurrence were analyzed using Kaplan-Meier curves and Mantel Log-Rank tests. Multivariate analysis was conducted using Cox-proportional hazards tests.  Black, obese, and diabetic women showed higher staining intensity in both tumor and stromal tissue. Strong tumor staining was associated with Black race, advanced stage, high grade obesity and diabetes. Strong stromal expression was associated with estrogen receptor positivity, and prediabetes/diabetes. Patients with strong tumor ALDH1A1 had shorter recurrence free and overall survival compared to those with moderate to low expression. When stratified by race, Black women with strong tumor ALDH1A1 expression had shorter recurrence free survival compared to White women. Strong tumor ALDH1A1 staining was an independent predictor of poor overall survival in both Black and White women. These findings indicate that ALDH1A1 expression is associated with poor outcomes in breast cancer, particularly in Black women, and provide the first link between tumor ALDH1A1 expression, obesity, and diabetes