Estrogen Receptor β Is Coexpressed with ERα and PR and Associated with Nodal Status, Grade, and Proliferation Rate in Breast Cancer

The role of estrogen (ER) and progesterone receptors (PR) in breast cancer is well established. Identification of the second human estrogen receptor, the estrogen receptor β (ERβ), prompted us to evaluate its role in breast cancer. We studied the expression of ERβ by immunohistochemistry and mRNA in situ hybridization in 92 primary breast cancers and studied its association with ERα, PR, and various other clinicopathological factors. Sixty percent of tumors were defined as ERβ-positive (nuclear staining in >20% of the cancer cells). Normal ductal epithelium and 5 of 7 intraductal cancers were also found to express ERβ. Three-fourths of the ERα- and PR-positive tumors were positive for ERβ, whereas ERα and PR were positive in 87% and 67. of ERβ-positive tumors, respectively. ERβ was associated with negative axillary node status ( P P = 0.0003), low S-phase fraction ( P = 0.0003), and premenopausal status ( P = 0.04). In conclusion, the coexpression of ERβ with ERα and PR as well as its association with the other indicators of low biological aggressiveness of breast cancer suggest that ERβ-positive tumors are likely to respond to hormonal therapy. The independent predictive value of ERβ remains to be established.