Estrogen receptors ß1 and ß2 are associated with distinct responses of estrogen receptor α-positive breast carcinoma to adjuvant endocrine therapy.

Our purpose was to assess whether and how ERß1 and/or ERß2 expression status could predict response of early stage ERα-positive breast carcinoma to adjuvant endocrine therapy (AET). ERß1 and ERß2 expression were determined using immunohistochemistry. ERß1- and ERß2-positivity were derived from receiver operating characteristic analysis and the median percentage of immunostained tumor cells, respectively. Patients with recurrent disease were grouped according to whether they relapsed within 4 years or after 4 years from surgery. The predictive significance of ERß1 and ERß2 was determined using Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. ERß1-positivity in the first-4-year relapse patient group was lower and ERß2-positivity in the post-4-year relapse group was higher compared with no-relapse group. ERß1-positivity was associated with lower tumor size and longer first-4-year disease-free survival, while ERß2-positivity was associated with shorter post-4-year disease-free survival. Cox multivariate analysis including ERß1, ERß2 and established clinico-pathological variables showed that ERß1-positivity was an independent predictor of lower first-4-year risk of relapse. Thus, low ERß1 expression and high ERß2 expression are markers for identification of AET-treated ERα-positive breast carcinoma patients at risk of early and late relapse, respectively.