[215] 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).

Table: ERα and ERβ status in normal TDLU in controls with BBD

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)

Conclusions: Our results suggest that ER-β expression in normal TDLUs in the absence of ER-α expression is associated with the contemporaneous presence of BBD with a low level of risk of subsequent breast cancer (i.e. non-proliferative lesions). Further, these data suggest that absence of ER-β expression in normal TDLUs is more common in women who develop breast cancer than in those who do not. This lends further support to the notion that ER-β, particularly in the absence of ER-α expression, may result in an anti-proliferative phenotype and reduced risk of breast cancer.
Category: Breast

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 18, Monday Morning