Oestrogen receptor beta in breast cancer prognosis and treatment

About 30 % of breast cancer patients do not respond to adjuvant tamoxifen treatment. In addition to classical clinical and pathological parameters, treatment decisions are based on the presence of the oestrogen receptor alfa, the progesterone receptor, and human epidermal growth factor 2 receptor. The inclusion of novel biomarkers in the estimation of breast cancer prognosis and in treatment decision-making could help improve patient outcomes. The objective of this study was to test whether the oestrogen receptor beta is associated with breast cancer prognosis and/or treatment response.

We collected data from the 118 breast cancer patients who had undergone surgery at the Institute of Oncology and Radiology of Serbia from 2002 to 2004.

We collected clinicopathological, treatment and survival data from 2002 to 2022. The data about oestrogen receptor beta protein, oestrogen receptor beta 1 and delta 5 variant mRNA and the oestrogen receptor beta promoter ON region methylation index were determined in our previous studies. We used the Kaplan-Meier test and log-rank test to estimate survival rates and differences in survival between patient groups.

In the exploratory subgroup analysis of patients with a high ERβ methylation index, tamoxifen use was associated with longer overall survival and disease-free survival (log-rank, p = 0.001; p = 0.033, respectively). In the subgroup of patients with a low ERβ methylation index, radiotherapy was associated with shorter disease-free survival (log-rank, p = 0.037).

This exploratory follow-up study investigates possible associations of oestrogen receptor beta expression and methylation with survival and treatment responses of breast cancer patients. Our results suggest that oestrogen receptor beta expression and methylation could be a significant additional marker of breast cancer prognosis to inform treatment decisions. These findings, derived from subgroup analyses, should be interpreted as hypothesis-generating and require validation in future studies.