Background: Germline mutations of BRCA1/BRCA2 genes are a cause of hereditary breast or ovarian cancer. Cancers arising in women with germline BRCA1/BRCA2 mutations are defective in DNA repair, and BRCA deficient cancer cells are hypersensitive to PARP inhibitors (Bryant et al., 2005;Farmer et al., 2005). Niraparib is a potent,selective inhibitor of PARP-1 and PARP-2 that demonstrated activity in BRCA1 or BRCA2 mutated cancer cell lines. Responses have been reported with Niraparib in women with BRCA1.2 related breast and ovarian cancer. (Michie et al, 2013). Methods: Patients with HER2 negative metastatic breast cancer (306), with centrally confirmed BRCA1 or BRCA2germline mutations, will be randomized 2:1 open-label study, to either niraparib 300mg (3x 100 mg niraparib capsules) administered orally QD continuously or physician’s choice of single-agent chemotherapy (eribulin, vinorelbine, capecitabine or gemcitabine) administered in 3 weekly cycles. Patients must have received prior therapy that included a taxane and anthracycline and should be pretreated with up to 2 prior cytotoxic regimens for advanced/metastatic disease. Patients with hormone receptor positive disease can be included if they progressed during one prior hormonal therapy. The primary objective is to compare the progression-free survival (PFS) (RECIST v 1.1) on niraparib versus physician’s choice, assessed by blinded, central review. The key secondary objective is to compare overall survival between patients in niraparib versus physician’s choice. Sample size is based on Overall Survival (OS). The hypothesis of median PFS improvement is 3 versus 6 months for physician’s choice and niraparib respectively, with a hazard ratio of 0.5, and power of 99.6% for the primary PFS analysis. Assuming an increase in OS from 9 to 13 months, the study has 80% power at a 1-sided alpha of 0.025. Secondary endpoints are PFS by investigator-based assessment, safety, time to treatment failure, Response Rate, Duration of response, HRQoL. This trial is enrolling patients from European, North American countries and Israel and is sponsored by TESARO. Clinical trial information: NCT01905592.