TY - JOUR
TI - Estrogen receptors β1 and β2 are associated with distinct responses of estrogen receptor α-positive breast carcinoma to adjuvant endocrine therapy
AU - Dhimolea, E.
AU - Tiniakos, D.G.
AU - Chantzi, N.T.
AU - Goutas, N.
AU - Vassilaros, S.D.
AU - Mitsiou, D.J.
AU - Alexis, T.N.
JO - Cancer Letter
PY - 2015
VL - 358
TODO - 1
SP - 37-42
PB - Elsevier Ireland Ltd
SN - null
TODO - 10.1016/j.canlet.2014.12.022
TODO - 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
TODO - 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.
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