BRCA1 and breast carcinoma: This finding is in contrast with previous reports, which typically suggest better outcomes for de novo metastatic breast cancer.39,40 One possible explanation for this discrepancy is that younger patients are more likely to carry BRCA1/2 pathogenic variants,41 which are associated with an aggressive disease course42 and possible diminished response to both ET and CDK4/6i treatment.43,44,45