Clinical and molecular data from a single institution cohort of CDK4/6i-treated HR+/HER2- mBC pts were analyzed….Cox regression showed a strong negative impact of gBRCA1/2-PALB2 on PFS (HR 4.0 CI 2.0–7.9) and OS (HR 3.5 CI 1.6–7.7)...Pathogenic gBRCA1/2-PALB2 and higher aneuploidy were associated with shorter survival.