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Martins and colleagues determined the order of BRCA1 LOH, PTEN loss, and TP53 mutation in single cells from breast tumors with germline BRCA1 mutations. Surprisingly, BRCA1 LOH was rarely the initiating event, and wild-type BRCA1 expression was not lost in every cell within a tumor. Instead, PTEN loss occurred first in the majority of cases, particularly in basal-like tumors, and TP53 mutation was the initiating event in most luminal tumors. These findings provide insight into the evolution of BRCA1-mutant breast cancers and suggest that BRCA1 loss is not a rate-limiting step in breast tumorigenesis. For details, please see the article by Martins and colleagues on page 503.