Inspired by the finding that a fraction of BRCA1-deficient human and mouse tumor cells harbor EMT features [16–19, 22–24, 39, 44], and the finding that E2 enhanced the heterogeneity of p18−/−;Brca1MGKO and p16−/−;Brca1MGKO tumors with elevated squamous metaplasia and spindle-shaped cells (typical morphological characteristics of mesenchymal cells), we hypothesized that estrogen promotes EMT and stimulates BRCA1-deficient, ER-negative tumorigenesis independent of ER. The gene discussed is ESR1; the disease is neoplasm.