Serum oestrogen receptor alpha and beta bioactivity are independently associated with breast cancer: a proof of principle study.

BACKGROUND: Oestrogens play a crucial role in breast carcinogenesis. Earlier studies have analysed the serum levels of endogenous hormones measured by conventional assays. In this study, we analysed the capacity of serum from breast cancer cases and controls to transactivate the oestrogen receptor alpha (ER-alpha) and beta (ER-beta). METHODS: We used a receptor oestrogen-responsive element (ERE) -- the green fluorescent protein (GFP)-reporter test system in Saccharomyces cerevisiae. Oestrogen receptor-alpha or ER-beta bioactivity was determined in serum from 182 randomly chosen postmenopausal women with breast cancer and from 188 age-matched controls. RESULTS: High serum ER-alpha and ER-beta bioactivity were independently associated with the presence of breast cancer. Women whose levels of serum ER-alpha and ER-beta bioactivity were in the highest quintile among controls had a 7.57-(95% confidence interval (CI): 2.46-23.32; P=0.0004) and a 10.14 (95% CI: 3.19-32.23; P<0.0001)-fold risk for general and oestrogen receptor-positive breast cancer, respectively. CONCLUSION: The use of serum ER-alpha and ER-beta bioactivity assays as clinical tools in the management of breast cancer warrants further research. Future studies will dictate whether surrogate markers of ER-alpha and ER-beta bioactivity will provide a means to monitor the efficacy of anti-endocrine, adjuvant and chemopreventive strategies.