Neadjuvant Multi-agent Chemotherapy or Letrozole Plus Ribociclib in Luminal B/HER2-negative Breast Cancer.

This is a parallel, two-arm, randomized 1:1, stratified by tumor size and nodal involvement, open-label, multicenter, exploratory study in postmenopausal women with primary operable HR+/HER2-negative Luminal B breast cancer according to PAM50 intrinsic subtype to evaluate the clinical benefit and biological effects of ribociclib combined with letrozole. The primary trial objective is to evaluate the ability of each treatment strategy to provide ROR-low score at surgery. Luminal B patients will be randomized 1:1 to either letrozole plus ribociclib or chemotherapy.Two weeks after the first administration of the assigned treatment, patients will undergo a biopsy to assess early biological response to treatment, at Ki67 protein and gene expression level. After finalization of the assigned neoadjuvant treatment, patients will undergo surgery. The primary endpoint, Rate of ROR-low (at surgery) after neoadjuvant treatment, according to the Prosigna test will be centrally assessed. Baseline, Day 15 and post-treatment (surgical) primary breast tumor tissue samples should be available for each patient for molecular characterization A post-surgery visit will be performed within 28 days (7 days) from surgery, and will mark the end of the study for that patient