Serum oestrogen receptor α and β bioactivity are independently associated with breast cancer: a proof of principle study

Abstract

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 a (ER-a) and b (ER-b). METHODS: We used a receptor oestrogen-responsive element (ERE) -the green fluorescent protein (GFP)-reporter test system in Saccharomyces cerevisiae. Oestrogen receptor-a or ER-b bioactivity was determined in serum from 182 randomly chosen postmenopausal women with breast cancer and from 188 age-matched controls. RESULTS: High serum ER-a and ER-b bioactivity were independently associated with the presence of breast cancer. Women whose levels of serum ER-a and ER-b bioactivity were in the highest quintile among controls had a 7.57-(95% confidence interval (CI): 2.46 -23.32; P ¼ 0.0004) and a 10.14 (95% CI: 3.19 -32.23; Po0.0001)-fold risk for general and oestrogen receptor-positive breast cancer, respectively. CONCLUSION: The use of serum ER-a and ER-b bioactivity assays as clinical tools in the management of breast cancer warrants further research. Future studies will dictate whether surrogate markers of ER-a and ER-b bioactivity will provide a means to monitor the efficacy of anti-endocrine, adjuvant and chemopreventive strategies.

Serum estrogen receptor bioactivity and breast cancer risk among postmenopausal women

“…In this study (Fourkala et al 2012), association between ERα-mediated bioactivity and breast cancer risk was only present in the subset of cases whose blood was collected more than 2 years before cancer diagnosis (Fourkala et al 2012). This contradicted the findings from a case-control study that the same group of investigators had conducted in Germany using blood collected from cases after clinical diagnosis, and which showed a strong association between ERα bioactivity and cancer risk (Widschwendter et al 2009). Differences between our study and that of the UK group could first be due to our use of mammalian cells, which are more physiologically relevant in differentiating between agonist and antagonist compared to yeast cell-based bioassays used by other investigators (Fourkala et al 2012; Widschwendter et al 2009).…”

“…This contradicted the findings from a case-control study that the same group of investigators had conducted in Germany using blood collected from cases after clinical diagnosis, and which showed a strong association between ERα bioactivity and cancer risk (Widschwendter et al 2009). Differences between our study and that of the UK group could first be due to our use of mammalian cells, which are more physiologically relevant in differentiating between agonist and antagonist compared to yeast cell-based bioassays used by other investigators (Fourkala et al 2012; Widschwendter et al 2009). In addition, the coregulators involved in transactivation of estrogen sensitive reporter genes has been reported to be differ between yeast and mammalian systems (Kohno, et al 1994).…”

“…In terms of breast cancer, the bioactivities of both ERα and ERβ have been shown to be independently associated with increased risk in European studies (Fourkala, et al 2012; Widschwendter, et al 2009). Specifically, in a case-control study conducted in Germany, women in the highest quintile of both serum ERα and ERβ bioactivities had approximately seven times the risk of breast cancer compared to women in lower levels of both receptor bioactivities (Widschwendter et al 2009).…”

“…Specifically, in a case-control study conducted in Germany, women in the highest quintile of both serum ERα and ERβ bioactivities had approximately seven times the risk of breast cancer compared to women in lower levels of both receptor bioactivities (Widschwendter et al 2009). More recently, in a case-control study nested in a cohort of women in UK, ERα bioactivity was shown to be independently associated with breast cancer risk in serum collected more than two years before diagnosis for breast cancer cases (Fourkala et al 2012).…”

Association of lifestyle and demographic factors with estrogenic and glucocorticogenic activity in Mexican American women

“…Cell-based reporter bioassays have been commonly used to identify estrogenic (E) compounds present in the environment (13)(14)(15)(16), but few studies have used them to test the association between overall E activity in human blood and breast cancer risk (17)(18)(19), as was originally proposed by Brouwers et al (20). An analysis conducted in samples collected prospectively from the Singapore Chinese Health Study tested the associations between levels of estrogens and estrogen receptor (ER)-mediated bioactivity and breast cancer risk among postmenopausal women and found results suggesting that factors other than estrone and estradiol may activate ER-mediated signaling pathways to increase breast cancer risk (19).…”