Breast cancer risk is higher in US-born than in foreign-born Hispanics/Latinas and also increases with greater length of US residency. It is only partially known what factors contribute to these patterns of risk. To gain new insights, we tested the association between lifestyle and demographic variables and breast cancer status, with measures of estrogenic (E) and glucocorticogenic (G) activity in Mexican American women. We used Chemical-Activated LUciferase gene eXpression assays to measure E and G activity in total plasma from 90 Mexican American women, without a history of breast cancer at the time of recruitment, from the San Francisco Bay Area Breast Cancer Study. We tested associations of nativity, lifestyle and sociodemographic factors with E and G activity using linear regression models. We did not find a statistically significant difference in E or G activity by nativity. However, in multivariable models, E activity was associated with Indigenous American ancestry (19% decrease in E activity per 10% increase in ancestry, P = 0.014) and with length of US residency (28% increase in E activity for every 10 years, P = 0.035). G activity was associated with breast cancer status (women who have developed breast cancer since recruitment into the study had 21% lower G activity than those who have not, P = 0.054) and alcohol intake (drinkers had 25% higher G activity than non-drinkers, P = 0.015). These associations suggest that previously reported breast cancer risk factors such as genetic ancestry and alcohol intake might in part be associated with breast cancer risk through mechanisms linked to the endocrine system.