Abstract B40: Estrogen receptor activity levels among Mexican American women

Background: Breast cancer incidence varies greatly worldwide. In particular, the incidence of breast cancer in Mexico is lower than that in the U.S. Individuals of Hispanic or Latino origin in the U.S. represent 16% of the total population and 38% of the population of California. The migratory experience is accompanied by changes in lifestyle and environmental exposures, which in turn modify the individual9s internal chemical environment. We expect that understanding the reasons behind breast cancer development in this seemingly protected population will be informative about relevant exposures that affect the probability of developing this disease more generally. Enzyme activation by exposure to hormone receptor disrupting compounds can lead to increased hormone catabolism, and compromise hormone signaling. Breast cancer is directly affected by the presence of endogenously produced hormones and likely also by hormone-like compounds of exogenous origin. We, therefore, used an untargeted cell-based assay to measure estrogen receptor activity among 90 Mexican American women from the San Francisco Bay Area Breast Cancer Study (SFBCS), 15 of whom developed breast cancer after blood sample collection. Methods: The estrogen receptor-mediated chemical-activated luciferase gene expression (ER-CALUX) assay was used to assess the presence of estrogenic substances in archived plasma for 90 U.S. Latina women. The plate design included multiple reference samples placed across and within plates. We first fitted a linear mixed effects model to the data including the technical sources of variation (plate as a random effect and row, column, row + column and row x column as fixed effects) and an indicator variable, to capture the distinct nature of the reference sample. Given that for each sample we had 4 measures of activity, we then fitted a linear mixed effect model using the residuals for the first regression, taking the individual level of variation into account, and including the following explanatory variables: case/control status, proportion of Indigenous American ancestry, menopausal status, use of hormone replacement therapy, use of oral contraceptives, socioeconomic status, education, body mass index and daily alcohol intake. Results: We did not observe a statistically significant difference between cases and controls in the estrogen receptor activity levels (p=0.12). We found a statistically significant difference in estrogen receptor activity levels by menopausal status in the expected direction, with mean equivalent estradiol level being 498±48 pM in pre-menopausal and 125±60 pM in post-menopausal women (p=0.001). Daily alcohol consumption also showed a statistically significant association with estrogen receptor activity levels (0.001), which disappeared when 1 woman with extremely high levels of daily alcohol consumption (75 Grams/daily) was excluded from the analysis (p=0.567). Conclusion: Despite the noisy nature of the untargeted measure of estrogen receptor activity, we were able to develop an experimental design that could capture technical variability and that allowed us to observed the expected association between levels of estrogen receptor activity and menopausal status in archived samples of U.S. Latina women. The present study included 15 women who developed breast cancer after specimen collection and 75 controls, and therefore was underpowered to detect modest differences between the two groups in estrogen receptor activity levels. Further studies are planned to examine this endpoint in a much larger sample set. Citation Format: Laura Fejerman, Reuben Thomas, Sylvia Sanchez, Phum Tachachartvanich, Esther M. John, Martyn Smith. Estrogen receptor activity levels among Mexican American women. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B40.