High Estrogen Receptor Beta Expression in Breast Cancer

Purpose: Isoform-specific tumor estrogen receptor beta (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, ERβ 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 five years). Associations between immunohistochemical ERβ1 expression, patient and tumor characteristics, as well as outcome within treatment groups were analyzed. Results: Tumor ERβ1 expression was available for 911 patients (89%), and was not associated with ERβ 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% CI 0.41-0.89). The magnitude of the association was larger in patients with ERα negative tumors (HR_adj 0.30: 95% CI 0.12-0.76), compared with ERα positive 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 to 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. Conclusions: 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.

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