@article{3088731, title = "Estrogen receptors β1 and β2 are associated with distinct responses of estrogen receptor α-positive breast carcinoma to adjuvant endocrine therapy", author = "Dhimolea, E. and Tiniakos, D.G. and Chantzi, N.T. and Goutas, N. and Vassilaros, S.D. and Mitsiou, D.J. and Alexis, T.N.", journal = "Cancer Letter", year = "2015", volume = "358", number = "1", pages = "37-42", publisher = "Elsevier Ireland Ltd", doi = "10.1016/j.canlet.2014.12.022", keywords = "estrogen receptor alpha; estrogen receptor beta; estrogen receptor beta1; estrogen receptor beta2; unclassified drug; estrogen receptor alpha; estrogen receptor beta, adult; aged; Article; cancer adjuvant therapy; cancer growth; cancer hormone therapy; cancer recurrence; cancer risk; cancer survival; controlled study; disease free survival; estrogen receptor positive breast cancer; female; human; human tissue; immunohistochemistry; major clinical study; predictive value; protein expression; receiver operating characteristic; treatment duration; tumor volume; adjuvant chemotherapy; biosynthesis; Breast Neoplasms; drug effects; gene expression regulation; genetics; metabolism; middle aged; Neoplasm Recurrence, Local; pathology; prognosis; very elderly, Adult; Aged; Aged, 80 and over; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Gene Expression Regulation, Neoplastic; Humans; Middle Aged; Neoplasm Recurrence, Local; Prognosis", abstract = "Our purpose was to assess whether and how ERβ1 and/or ERβ2 expression status could predict response of early stage ERα-positive breast carcinoma to adjuvant endocrine therapy (AET). ERβ1 and ERβ2 expression were determined using immunohistochemistry. ERβ1- and ERβ2-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 ERβ1 and ERβ2 was determined using Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. ERβ1-positivity in the first-4-year relapse patient group was lower and ERβ2-positivity in the post-4-year relapse group was higher compared with no-relapse group. ERβ1-positivity was associated with lower tumor size and longer first-4-year disease-free survival, while ERβ2-positivity was associated with shorter post-4-year disease-free survival. Cox multivariate analysis including ERβ1, ERβ2 and established clinico-pathological variables showed that ERβ1-positivity was an independent predictor of lower first-4-year risk of relapse. Thus, low ERβ1 expression and high ERβ2 expression are markers for identification of AET-treated ERα-positive breast carcinoma patients at risk of early and late relapse, respectively. © 2014 Elsevier Ireland Ltd." }