RAD51-foci Score Predicts Olaparib Efficacy in Advanced HER2-negative Breast Cancer

Status: COMPLETED | Phase: PHASE2 Condition(s): HER2-negative Breast Cancer, Metastatic Breast Cancer, Triple Negative Breast Cancer Intervention(s): Olaparib (DRUG) The primary objetive is to assess the capacity of the RAD51-foci score to predict the efficacy of olaparib in BRCA1/2, PALB2 or RAD51C/D mut advanced breast cancer (cohort 1). The investigators propose the hypothesis that the RAD51-foci low tumours determined by immunofluorescence using RAD51 assay in patients with BRCA1/2, PALB2 \& RAD51C/D mutation (cohort 1) predicts response to olaparib. Furthermore, The investigators posit that the determination of RAD51-foci score in tumour identifies patients who can benefit from olaparib beyond mutations in these 5 genes. This hypothesis will be tested in cohort 2. Detailed: This is an open-label, single arm, multicentre phase II study evaluating treatment with olaparib in patients with unresectable locally advanced or metastatic breast cancer (MBC) in two cohorts: 1. with mutation in germline/somatic BRCA1/2, PALB2 or RAD51C/D and 2. RAD51-foci low score in wild type HRR tumours or without known deleterious BRCA1/2, PALB2 or RAD51C/D mutations at study entry. Although efficacy and safety will be investigated. The primary objective consists in identifying a predictive biomarker for clinical benefit of treatment with olaparib. All patients recruited in the study will be selected based on the following 3 principles: * Genetic selection: * Cohort 1: HER2-negative ABC with documented germline or somatic mutation in BRCA1, BRCA2, PALB2, RAD51C or RAD51D that Primary Outcome(s): Capacity of the RAD51-foci score to predict the efficacy of olaparib in BRCA1/2, PALB2 or RAD51C/D mut advanced breast cancer (cohort 1) Enrollment: 65 (ACTUAL) Lead Sponsor: SOLTI Breast Cancer Research Group Start: 2022-03-25 | Primary Completion: 2025-02-03