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

Purpose: Isoform-specific tumor estrogen receptor beta (ER beta) expression may hold prognostic information in breast cancer, especially among endocrine-treated breast cancer patients. The study's purpose was to evaluate ER beta isoform 1 (ER beta 1) expression in relation to tumor characteristics, ESR2 genotypes, and prognosis in different treatment groups. Experimental Design: 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 ER beta 1 expression, patient and tumor characteristics, as well as outcome within treatment groups were analyzed. Results: Tumor ER beta 1 expression was available for 911 patients (89%) and was not associated with ESR2 genotypes. ER beta 1 positivity, defined as > 75% (ER beta 1(75)(+), 72.7%), was positively associated with established favorable tumor characteristics. Overall, ER beta 1(75)(+) was associated with lower risk of breast cancer events [HRadj = 0.60; 95% confidence interval (CI), 0.41-0.89]. The magnitude of the association was larger in patients with ER alpha(-) tumors (HRadj = 0.30; 95% CI, 0.12-0.76), compared with ER alpha(+) tumors (HRadj = 0.66; 95% CI, 0.42-1.03). Among the 232 chemotherapy-treated patients, ER beta 1(75)(+) tumors were associated with lower risk of breast cancer events compared with ER beta 1(75)(-) tumors (HRadj = 0.31; 95% CI, 0.15-0.64). Among the 671 chemonaive patients, ER beta 1(75) status was not associated with the outcome. Conclusions: High ER beta 1 expression was a favorable prognostic marker in this breast cancer cohort, especially in chemotherapytreated patients, but not in endocrine therapy-treated patients. These results warrant confirmation, preferably via a biomarker study in a previously conducted randomized trial. (C) 2016 AACR.