Estrogen receptor-β expression in invasive breast cancer in relation to molecular phenotype: Results from the nurses' health study

Abstract

The expression of estrogen receptor-α (ER-α) and related genes has emerged as one of the major determinants of molecular classification of invasive breast cancers. Expression of a second ER, estrogen receptor-Β (ER-Β), has not been previously evaluated in a large population-based study. Therefore, we examined ER-Β expression in a large population of women with breast cancer to assess its relationship to molecular categories of invasive breast cancer. We constructed tissue microarrays from paraffin blocks of 3093 breast cancers that developed in women enrolled in the Nurses' Health Study. Tissue microarray sections were immunostained for ER-α, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6, epidermal growth factor receptor (EGFR) and with a monoclonal antibody to ER-Β. Cancers were categorized as luminal A (ER-α and/or PR and HER2-); luminal B (ER-α and/or PR and HER2); HER2 (ER-α and PR and HER2); and basal-like (ER-α, PR, HER2 and EGFR or cytokeratin 5/6). The relationship between expression of ER-Β and molecular class of invasive breast cancer was analyzed. Overall, 68% of breast carcinomas were ER-Β. Expression of ER-Β was significantly associated with expression of ER-α (P>0.0001) and PR (P>0.0001), and was inversely related to expression of HER2 (P=0.004), CK5/6 (P=0.02) and EGFR (P0.006). Among 2170 invasive cancers with complete immunophenotypic data, 73% were luminal A, 5% luminal B, 6 % HER2 and 11% basal-like. ER-Β expression was significantly related to molecular category (P>0.0001) and was more common in luminal A (72% of cases) and B (68% of cases) than in HER2 or basal-like types. However, despite their being defined by the absence of ER-α expression, 55% of HER2-type and 60% of basal-like cancers showed expression of ER-Β. The role of ER-Β in the development and progression of breast cancers defined by lack of expression of ER-α merits further investigation. © 2010 USCAP, Inc. All rights reserved.