Abstract
BACKGROUND: Triple-negative breast cancers comprise 15% of breast cancers and are more common in women with BRCA1 mutations. Although most have basal gene expression signatures, others resemble luminal tumors with expression of androgen receptor-related genes and some express the immunoinhibitory protein programmed death-ligand 1 (PD-L1). Given the availability of androgen receptor-targeted and immune therapies for triple-negative breast cancers, determining predictors of these biomarkers is important. AIMS: To determine the prevalence and predictors of androgen receptor and PD-L1 expression in BRCA1-associated and sporadic triple-negative breast cancer. METHODS: We studied 197 triple-negative breast cancers: 78 (39.6%) from BRCA1 mutation carriers and 119 (60.4%) from noncarriers. Tumor pathology was reviewed and tissue microarray sections were immunostained for androgen receptor and PD-L1. RESULTS: Androgen receptor expression was seen in 18% of tumors and was significantly less common in tumors from BRCA1 mutation carriers than noncarriers (9.2 vs. 23.7%; P=0.01). Twenty-six percent of cancers expressed PD-L1 with no significant difference in frequency between carriers and noncarriers. Factors predicting androgen receptor expression were lower histologic grade (odds ratio (OR) 4.6; 95% confidence interval (CI) 1.1-19.7), older age at diagnosis (OR 1.3; 95% CI 1.03-1.7) and PD-L1 expression (OR 2.6; 95% CI 1.1-6.1). PD-L1 expression was significantly more common in cancers with lymphocytic infiltrates (OR, 3.3; 95% CI 1.1-10.4) and androgen receptor expression (OR, 3.2; 95% CI 1.4-7.5), and less common in tumors with lymphovascular invasion (OR 0.41; 95% CI 0.18-0.92). CONCLUSIONS: These results identify predictors for androgen receptor and PD-L1 expression among triple-negative breast cancers that may lead to better treatment selection and participation in clinical trials.