PARP enzymes are essential for DNA damage repair. Cancers with defective homologous recombination DNA repair, such has BRCA1- and BRCA2-mutated breast cancers, are targets for PARP inhibitors (PARPi) through the exploitation of synthetic lethality. A number of PARPi are currently undergoing clinical evaluation in breast cancer, with olaparib and talazoparib having demonstrated superior efficacy compared with standard chemotherapy in advanced germline BRCA-mutated cancer. This review describes the biological rationale for PARPi and presents the accumulating data on PARPi use in breast cancer.
Tomas G. Lyons and Mark E. Robson
Paul F. Engstrom, Mara G. Bloom, George Daniel Demetri, Phillip G. Febbo, William Goeckeler, Marc Ladanyi, Bryan Loy, Kate Murphy, Michael Nerenberg, Paul Papagni, Mark Robson, Robert W. Sweetman, Sean Tunis, Jessica DeMartino and Jonathan K. Larsen
Personalized medicine in oncology is maturing and evolving rapidly, and the use of molecular biomarkers in clinical decision-making is growing. This raises important issues regarding the safe, effective, and efficient deployment of molecular tests to guide appropriate care, specifically regarding laboratory-developed tests and companion diagnostics. In May 2011, NCCN assembled a work group composed of thought leaders from NCCN Member Institutions and other organizations to identify challenges and provide guidance regarding molecular testing in oncology and its corresponding utility from clinical, scientific, and coverage policy standpoints. The NCCN Molecular Testing Work Group identified challenges surrounding molecular testing, including health care provider knowledge, determining clinical utility, coding and billing for molecular tests, maintaining clinical and analytic validity of molecular tests, efficient use of specimens, and building clinical evidence.
Mary B. Daly, Robert Pilarski, Jennifer E. Axilbund, Michael Berry, Saundra S. Buys, Beth Crawford, Meagan Farmer, Susan Friedman, Judy E. Garber, Seema Khan, Catherine Klein, Wendy Kohlmann, Allison Kurian, Jennifer K. Litton, Lisa Madlensky, P. Kelly Marcom, Sofia D. Merajver, Kenneth Offit, Tuya Pal, Huma Rana, Gwen Reiser, Mark E. Robson, Kristen Mahoney Shannon, Elizabeth Swisher, Nicoleta C. Voian, Jeffrey N. Weitzel, Alison Whelan, Myra J. Wick, Georgia L. Wiesner, Mary Dwyer, Rashmi Kumar and Susan Darlow
The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling and risk assessment and management for hereditary cancer syndromes. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meeting. Major discussion topics this year included multigene testing, risk management recommendations for less common genetic mutations, and salpingectomy for ovarian cancer risk reduction. The panel also discussed revisions to genetic testing criteria that take into account ovarian cancer histology and personal history of pancreatic cancer.