title: Estrogen receptors β1 and β2 are associated with distinct responses of estrogen receptor α-positive breast carcinoma to adjuvant endocrine therapy.
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.
authors.affiliation: Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Av, 11635 Athens, Greece.
authors.forename: Eugen
authors.initials: E
authors.lastname: Dhimolea
authors.affiliation: Laboratory of Histology & Embryology, Medical School, University of Athens, 75 M. Asias str., 11527 Athens, Greece.
authors.forename: Dina G
authors.initials: DG
authors.lastname: Tiniakos
authors.affiliation: Laboratory of Histology & Embryology, Medical School, University of Athens, 75 M. Asias str., 11527 Athens, Greece.
authors.forename: Νiki Ι
authors.initials: ΝΙ
authors.lastname: Chantzi
authors.affiliation: Department of Pathology, Eugenideio Infirmary, 20 Papadiamantopoulou str., 11528 Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Goutas
authors.affiliation: "Prolipsis" Medical Centre, 3 Sevastias str., 11528 Athens, Greece.
authors.forename: Stamatis D
authors.initials: SD
authors.lastname: Vassilaros
authors.affiliation: Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Av, 11635 Athens, Greece.
authors.forename: Dimitra J
authors.initials: DJ
authors.lastname: Mitsiou
authors.affiliation: Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Av, 11635 Athens, Greece. Electronic address: mnalexis@eie.gr.
authors.forename: Μichael N
authors.initials: ΜN
authors.lastname: Alexis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000096:biosynthesis*; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011379:Prognosis
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta
keywords: Breast carcinoma; ERβ1; ERβ2; Endocrine therapy; Immunohistochemistry