Estrogen receptor beta is coexpressed with ER alpha 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 beta (ER beta), prompted us to evaluate its role in breast cancer. We studied the expression of ER beta by immunohistochemistry and mRNA in situ hybridization in 92 primary breast cancers and studied its association with ER alpha, PR, and various other clinicopathological factors. Sixty percent of tumors were defined as ER beta-positive (nuclear staining in >20% of the cancer cells). Normal ductal epithelium and 5 of 7 intraductal cancers were also found to express ER beta, Three-fourths of the ER alpha- and PR-positive tumors were positive for ER beta, whereas ER alpha and PR were positive in 87% and 67% of ER beta-positive tumors, respectively, ER beta was associated with negative axillary node status (P < 0.0001), low grade (P = 0.0003), low S-phase fraction (P = 0.0003), and premenopausaI status (P = 0.04). In conclusion, the coexpression of ER beta with ER alpha and PR as well as its association with the other indicators of low biological aggressiveness of breast cancer suggest that ER beta-positive tumors are likely to respond to hormonal therapy. The independent predictive value of ER beta remains to be established.