Extended Data Fig. 9. Proposed model of breast cancer initiation in BRCA1/2 carriers.

In the proposed model, CNAs that accumulate in normal breast tissues (for example, 1q-gain and 10q or 16q-loss) would enhance the fitness of the luminal epithelial cells. In BRCA1/2 mutation carriers, where inactivation of the wild-type (WT) copy of BRCA1/2 leads to defective DNA repair, genomic instability and apoptosis, luminal cells carrying these CNAs would be more tolerant of these stresses, thus allowing the homologous-recombination defective mutant cells to expand, acquire oncogenic mutations, and ultimately progress to cancer.