Homologous recombination proficiency in ovarian and breast cancer patients
Justin F. Creeden, Nisha S. Nanavaty, Katelyn R. Einloth, Cassidy Gillman, Laura Stanbery, Danae Hamouda, Lance D. Dworkin, John Nemunaitis
Abstract
Homologous recombination and DNA repair are important for genome maintenance. Genetic variations in essential homologous recombination genes, including BRCA1 and BRCA2 results in homologous recombination deficiency (HRD) and can be a target for therapeutic strategies including poly (ADP-ribose) polymerase inhibitors (PARPi). However, response is limited in patients who are not HRD, highlighting the need for reliable and robust HRD testing. This manuscript will review BRCA1/2 function and homologous recombination proficiency in respect to breast and ovarian cancer. The current standard testing methods for HRD will be discussed as well as trials leading to approval of PARPi's. Finally, standard of care treatment and synthetic lethality will be reviewed.