Date Published: March 25, 2019
Publisher: Public Library of Science
Author(s): Sylvia S. Sanchez, Phum Tachachartvanich, Frank Z. Stanczyk, Scarlett L. Gomez, Esther M. John, Martyn T. Smith, Laura Fejerman, Andrea Cignarella.
Estrogens play a significant role in breast cancer development and are not only produced endogenously, but are also mimicked by estrogen-like compounds from environmental exposures. We evaluated associations between estrogenic (E) activity, demographic factors and breast cancer risk factors in Non-Latina Black (NLB), Non-Latina White (NLW), and Latina women. We examined the association between E activity and Indigenous American (IA) ancestry in Latina women. Total E activity was measured with a bioassay in plasma samples of 503 women who served as controls in the San Francisco Bay Area Breast Cancer Study. In the univariate model that included all women with race/ethnicity as the independent predictor, Latinas had 13% lower E activity (p = 0.239) and NLBs had 35% higher activity (p = 0.04) compared to NLWs. In the multivariable model that adjusted for demographic factors, Latinas continued to show lower E activity levels (26%, p = 0.026), but the difference between NLBs and NLWs was no longer statistically significant (p = 0.431). An inverse association was observed between E activity and IA ancestry among Latina women (50% lower in 0% vs. 100% European ancestry, p = 0.027) consistent with our previously reported association between IA ancestry and breast cancer risk. These findings suggest that endogenous estrogens and exogenous estrogen-like compounds that act on the estrogen receptor and modulate E activity may partially explain racial/ethnic differences in breast cancer risk.
Epidemiological studies have consistently reported that endogenous sex hormones play a critical role in the etiology of numerous diseases including breast cancer [1–4]. Interestingly, among U.S. racial/ethnic groups the reported variation in endogenous hormone levels is consistent with observed racial/ethnic differences in the incidence of breast cancer [5–7]. For example, in the Women’s Health Initiative Dietary Modification Trial, African American women had significantly higher concentrations of endogenous reproductive hormones compared to non-Latina White women , whereas higher levels of urinary concentrations of estrogens were strongly associated with breast cancer risk in Asian women in the Shanghai Women’s Study cohort . Moreover, in the Multiethnic Cohort study, postmenopausal Native Hawaiian and African American women tended to have higher levels of endogenous hormones when compared to non-Latina Whites (NLWs) , while foreign-born Hispanic/Latina women (referred to as Latinas hereafter) had lower hormone levels which correlates with their lower incidence of breast cancer .
Descriptive characteristics by racial/ethnic groups are presented in Table 1. After adjusting for plate, ER RLUs were highest for NLB women (mean of 8844 RLUs), followed by NLWs (mean of 8155 RLUs), and lowest for Latina women (mean RLUs of 6226). NLW women were older at blood draw (66.8 yrs, sd. 10.5 yrs) when compared to NLB (61.7 yrs, sd. 9.8 yrs) and Latina (61.5 yrs, sd. 9.5 yrs) women. Age at menarche was similar for the three groups. NLB women had the lowest age at first full term pregnancy (21 yrs, sd. 5 yrs). However, Latina women had a greater number of full term pregnancies (3.8) compared to the NLW (2.4) and NLB women (2.8). Latina women were on average shorter than NLBs and NLWs. A large percentage (66%) of the Latina women in this study were foreign-born, while over 90% of the NLW and NLB women were U.S.-born. About 87% and 84% of the Latina and NLB women, respectively, were categorized as overweight or obese. A greater proportion of NLW women reported consuming some alcohol (54%), while 76% and 71% of NLB and Latina women, respectively, reported no alcohol intake during the year before the interview. Lastly, women in this study were predominantly postmenopausal either naturally or due to surgery. Although a statistically significant greater proportion (27%) of NLB women had a history of hysterectomy and/or oophorectomy compared to NLW and Latina women, menopausal status did not differ between the three racial/ethnic groups.
Our study shows that there are significant differences in E activity in women across three racial/ethnic groups, partly due to differences in BMI (in the case of NLWs vs. NLBs) and potential exposure to exogenous estrogen-like compounds (NLWs vs. Latinas). Results also suggest that higher IA ancestry in Latina women is associated with lower levels of E activity, which is consistent with the observation that Latina women with high IA ancestry have lower risk of developing breast cancer.
Given the central role of the activation of the ER in the etiology of breast cancer, a better understanding of the receptor’s interaction with the receptor ligands, whether endogenous or exogenous, is imperative. Additionally, the discovery of specific compounds that are modulating the receptor and are present at different levels in different populations, would lead to changes in exposure to these compounds and ultimately, to changes in breast cancer risk.