High Estrogen Receptor β Expression Is Prognostic among Adjuvant Chemotherapy-Treated Patients-Results from a Population-Based Breast Cancer Cohort.

Abstract

Isoform-specific tumor estrogen receptor β (ERβ) expression may hold prognostic information in breast cancer, especially among endocrine-treated breast cancer patients. The study's purpose was to evaluate ERβ isoform 1 (ERβ1) expression in relation to tumor characteristics, ESR2 genotypes, and prognosis in different treatment groups. A population-based prospective cohort of 1,026 patients diagnosed with primary invasive breast cancer in Lund, Sweden, between October 2002 and June 2012 was followed until June 2014 (median 5 years). Associations between immunohistochemical ERβ1 expression, patient and tumor characteristics, as well as outcome within treatment groups were analyzed. Tumor ERβ1 expression was available for 911 patients (89%) and was not associated with ESR2 genotypes. ERβ1 positivity, defined as >75% (ERβ1₇₅⁺, 72.7%), was positively associated with established favorable tumor characteristics. Overall, ERβ1₇₅⁺ was associated with lower risk of breast cancer events [HR_adj = 0.60; 95% confidence interval (CI), 0.41-0.89]. The magnitude of the association was larger in patients with ERα^- tumors (HR_adj = 0.30; 95% CI, 0.12-0.76), compared with ERα⁺ tumors (HR_adj = 0.66; 95% CI, 0.42-1.03). Among the 232 chemotherapy-treated patients, ERβ1₇₅⁺ tumors were associated with lower risk of breast cancer events compared with ERβ1₇₅^- tumors (HR_adj = 0.31; 95% CI, 0.15-0.64). Among the 671 chemonaïve patients, ERβ1₇₅ status was not associated with the outcome. High ERβ1 expression was a favorable prognostic marker in this breast cancer cohort, especially in chemotherapy-treated patients, but not in endocrine therapy-treated patients. These results warrant confirmation, preferably via a biomarker study in a previously conducted randomized trial. Clin Cancer Res; 23(3); 766-77. ©2016 AACR.