Cheng TYD, Yao S, Omilian AR, et al. - Given that luminal differentiation is promoted by forkhead box protein A1 (FOXA1), and a possible mechanism of developing estrogen receptor-negative (ER-) breast cancer could be hypermethylation of the gene, so, researchers assessed FOXA1 in breast tumor and adjacent normal tissue in relation to reproductive factors, especially higher parity and no breastfeeding, that are linked with ER- tumors. In the Women's Circle of Health Study, including 949 Blacks and 380 Whites, they did immunohistochemistry for FOXA1 in 1,329 breast tumors and 298 adjacent-normal tissues. Via histology (H) scores, they summarized protein expression levels. Higher FOXA1 protein expression was noted in ER+ vs ER- tumors. Among women with ER+ or non-triple-negative cancer, they found higher FOXA1 expression in tumor vs paired adjacent-normal tissue, no such finding was reported in women with ER- or triple-negative cancer. The findings of this tumor-based study revealed a link between higher parity and lower FOXA1 expression in ER+ tumors, as well as demonstrated the possible amelioration of the effect by breastfeeding.