Estrogen Receptor-beta Expression in Normal Breast Tissue in Relation to Benign Breast Disease Category and Breast Cancer Risk: Results from the Nurses' Health Study
J Hilson, Y Wang, J Connolly, S Schnitt, L Collins, R Tamimi. Beth Israel Deaconess Medical Center, Boston; Montefiore Medical Center, Bronx; Channing Institute, Boston
Background: Estrogen receptor alpha (ER-α) and estrogen receptor beta (ER-β) are expressed in normal breast tissue, benign breast lesions and breast cancers but their relative importance in tumor progression is poorly-defined. We investigated the relation between ER-α and ER-β expression, benign breast disease (BBD) and breast cancer risk.
Design: Using a nested case-control design, we examined ER-α and ER-β expression in normal terminal duct lobular units (TDLUs) in relation to category of BBD and breast cancer risk among women in the Nurses' Health Study. We constructed tissue microarrays (TMAs) of normal TDLUs from benign breast biopsies and immunostained TMA sections for ER-α and ER-β. 246 women had normal TDLUs in the TMAs and evaluable ER-α and ER-β; 59 subsequently developed breast cancer and 187 did not. Epithelial cells in normal TDLUs were scored for ER-α and ER-β with positivity considered as >10% and >30% of nuclei staining, respectively.
Results: ER-α and ER-β expression in normal TDLUs in relation to category of BBD is shown in the Table. Women whose TDLUs were ERα-/ERβ+ more often had non-proliferative than proliferative lesions with or without atypia than those with other combinations of ERα/ERβ staining (p=0.007). In addition, absence of ER-β expression in normal TDLUs was twice as frequent among women who developed breast cancer (7.9%) than those who did not (4%), though this difference was not statistically significant (p=0.17).
|ERα/ERβ status||Non proliferative disease (%)||Proliferative disease without atypia (%)||Atypical hyperplasia (%)|
|ERα- ERβ-||2 (4.2)||0 (0)||0 (0)|
|ERα- ERβ+||9 (18.8)||7 (7.2)||1 (2.4)|
|ERα+ ERβ-||0 (0)||6 (6.2)||1 (2.4)|
|ERα+ ERβ+||37 (77.1)||84 (86.6)||40 (95.2)|