Cyclin E1 Expression and Palbociclib Efficacy in Previously Treated Hormone Receptor–Positive Metastatic Breast Cancer

PURPOSEA large-panel gene expression analysis was conducted to identify biomarkers associated with the effectiveness of adding palbociclib to fulvestrant.METHODSThe PALOMA-3 (ClinicalTrials.gov identifier: NCT01942135) trial randomly assigned 521 endocrine-pretreated patients with metastatic breast cancer to receive palbociclib plus fulvestrant or placebo plus fulvestrant. Primary analysis was first conducted on 10 genes on the basis of pathway biology and evidence from previous studies followed by a systematic panel-wide search among 2,534 cancer-related genes. The association of gene expression with the effect of palbociclib on progression-free survival (PFS) was evaluated using Cox proportional hazards regression analysis, with gene expression as a continuous variable or dichotomized by median. An independent breast cancer cohort from the Preoperative Palbociclib (POP) Clinical Trial (ClinicalTrials.gov identifier: NCT02008734) was used for validation, in 61 patients with primary breast cancer treated ...