Abstract P5-08-27: Estrogen receptor beta expression is prognostic among chemotherapy-treated patients – Results from a population-based breast cancer cohort
Authors: Elebro K , Borgquist S , Rosendahl A , Markkula A , Simonsson M , Jirström K , Rose C , Ingvar C , Jernström H 
Published: May 2016

Abstract
Background and aim
Estrogen receptor beta (ERβ) expression has been suggested to hold prognostic and predictive information, especially for endocrine treatment. The role of ERβ may depend on the expression of estrogen receptor alpha (ERα). The aim of this study was to evaluate ERβ expression in relation to tumor characteristics and risk for early events (disease-free survival, DFS) – overall and in different treatment groups, in a population-based cohort of primary breast cancer patients.
Materials and methods
Patients with primary breast cancer were invited at the preoperative visit between October 2002 and June 2012. After exclusion of patients who received preoperative treatment and patients with in situ carcinoma, the study population consisted of 1026 patients. Tumor specimens mounted in tissue microarrays were analyzed for ERβ expression using immunohistochemistry (antibody PPG5/10, Dako, dilution 1:20). Two cut-offs for positivity were evaluated (&gt;10% and &gt;75% of stained nuclei, respectively). Cox regression analyses yielding hazard ratios (HRs) with 95% confidence intervals (CIs) were adjusted for ERα status, tumor size, axillary lymph node involvement, histological grade, age at inclusion and body mass index. Events were defined as ipsi- or contralateral recurrences, regional or distant metastases. DFS was calculated from inclusion to event, non-breast cancer related death or last follow-up by June 30 2014, whichever came first. Patients were followed for up to 11 years (median follow-up 5.0 years for patients still at risk).
Results
ERβ expression was available for 911 patients (89%). ERβ positivity defined as &gt;10% (ERβ10+, 92.1%) was positively associated with ERα (P&lt;0.0001). ERβ10+ was not associated with DFS, overall or in patients who received tamoxifen and/or aromatase inhibitors. ERβ positivity defined as &gt;75% (ERβ75+, 72.7%) was associated with ERα and PR positivity, lower histological grade, smaller invasive tumor size and no involvement of axillary nodes (all Ps≤0.03). In survival analyses among all patients, ERβ75+ was inversely associated with risk of early events (LogRank P=0.0005, adjHR 0.62: 95% CI 0.42-0.90; P=0.013). The magnitude of the association was larger in patients with ERα negative tumors (LogRankERα- P=0.011, adjHRERα- 0.42: 95% CI 0.17-1.02; P=0.05) compared to patients with ERα positive tumors (LogRankERα+ P=0.069, adjHRERα+ 0.74: 95% CI 0.48-1.14; P=0.18). In analyses stratified for chemotherapy, ERβ75+ expression was significantly associated with lower risk of early events among the 232 patients who had received chemotherapy (Log Rank P=0.0005, adjHR 0.31: 95% CI 0.15-0.63; P=0.001), but not among the 670 patients without chemotherapy (Log Rank P=0.14, adjHR 0.81: 95% CI 0.50-1.31; P=0.38). ERβ75+ was not associated with early events in patients with ERα+ tumors who received tamoxifen and/or aromatase inhibitors.
Conclusion
This study provides support for high tumor ERβ expression as a prognostic marker in breast cancer, for patients who received chemotherapy. Previous reports of ERβ as a predictor of endocrine therapy response could not be confirmed.
Citation Format: Elebro K, Borgquist S, Rosendahl A, Markkula A, Simonsson M, Jirström K, Rose C, Ingvar C, Jernström H. Estrogen receptor beta expression is prognostic among chemotherapy-treated patients – Results from a population-based breast cancer cohort. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-27.