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

ABSTRACT

PURPOSE: Isoform-specific tumor estrogen receptor ß (ERß) expression may hold prognostic information in breast cancer, especially among endocrine-treated breast cancer patients. The study's purpose was to evaluate ERß isoform 1 (ERß1) 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 ERß1 expression, patient and tumor characteristics, as well as outcome within treatment groups were analyzed. RESULTS: Tumor ERß1 expression was available for 911 patients (89%) and was not associated with ESR2 genotypes. ERß1 positivity, defined as >75% (ERß175+, 72.7%), was positively associated with established favorable tumor characteristics. Overall, ERß175+ 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 ERα- tumors (HRadj = 0.30; 95% CI, 0.12-0.76), compared with ERα+ tumors (HRadj = 0.66; 95% CI, 0.42-1.03). Among the 232 chemotherapy-treated patients, ERß175+ tumors were associated with lower risk of breast cancer events compared with ERß175- tumors (HRadj = 0.31; 95% CI, 0.15-0.64). Among the 671 chemonaïve patients, ERß175 status was not associated with the outcome. CONCLUSIONS: High ERß1 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.