Preclinical data from our laboratory demonstrate that oestrogen and oestrogen metabolites cause DNA double strand breaks (DSBs) in ER-negative breast cells (normal and cancer cell lines, as well as primary breast progenitor cells isolated from patients), and that BRCA1 is necessary for repression and repair of these DSBs.17 The implication of these findings is that in BRCA1-deficient breast cells, exposure to oestrogen and its metabolites is capable of driving genomic instability, a well-defined early event in BRCA1-related cancer development.18 19. The gene discussed is BRCA1; the disease is cancer.