Homologous recombination defects in sporadic breast cancers

22102 Background: Homologous Recombination (HR) is the only mechanism that can reliably repair double-strand DNA breaks. Alternative DNA repair mechanisms, such as non-homologous end joining exist, but these induce DNA mutations and chromosomal aberrations. Hence, tumors that have deregulating mutations in the key players of HR are extremely sensitive to DNA damaging agents, such as bifunctional alkylators and are targeted specifically by Poly(ADP-ribose) Polymerase (PARP) inhibiting drugs. Defects in homologous recombination arise through dysfunction of BRCA1 or BRCA2 or by abnormalities in the Fanconi Anemia pathway. In addition, the recently discovered oncogene EMSY is amplified in a subgroup of breast tumors and blocks HR by inactivating the Brca2 protein. HR defects have been reported to be present in up to 30% of sporadic breast cancers. This study was designed to develop a clinically useful test to identify patients with tumors deficient in homologous recombination. Methods: We have prospectively t...