Association Between BRCA 1 and BRCA 2 Mutations and Survival in Women With Invasive Epithelial Ovarian Cancer

Kelly L. Bolton, PhD, Georgia ChenevixTrench, PhD, Cindy Goh, BA, Siegal Sadetzki, MD, MPH, Susan J. Ramus, PhD, Beth Y. Karlan, MD, Diether Lambrechts, PhD, Evelyn Despierre, MD, Daniel Barrowdale, BSc, Lesley McGuffog, Sue Healey, BSc, Douglas F. Easton, PhD, Olga Sinilnikova, PhD, Javier Benı́tez, PhD, Marı́a J. Garcı́a, PhD, Susan Neuhausen, PhD, Mitchell H. Gail, MD, PhD, Patricia Hartge, ScD, Susan Peock, PhD, Debra Frost, ONC, D. Gareth Evans, MBBS, MRCP, MD, FRCP, Rosalind Eeles, PhD, MA, FRCP, FRCR, Andrew K. Godwin, PhD, Mary B. Daly, MD, PhD, Ava Kwong, MBBS, FRCS, Edmond S. K. Ma, MD, Conxi Lázaro, PhD, Ignacio Blanco, MD, PhD, Marco Montagna, PhD, Emma D’Andrea, MD, PhD, Maria Ornella Nicoletto, MD, Sharon E. Johnatty, PhD, Susanne Krüger Kjær, MD, DMSc, Allan Jensen, PhD, Estrid Høgdall, PhD, Ellen L. Goode, PhD, Brooke L. Fridley, PhD, Jennifer T. Loud, DNP, Mark H. Greene, MD, Phuong L. Mai, MD, Angela Chetrit, MSc, Flora Lubin, MSc, Galit Hirsh-Yechezkel, PhD, Gord Glendon, MSc, Irene L. Andrulis, PhD, Amanda E. Toland, PhD, Leigha Senter, MS, Martin E. Gore, MBBS, PhD, FRCP, Charlie Gourley, PhD, FRCP, Caroline O. Michie, MD, Honglin Song, PhD, Jonathan Tyrer, PhD, Alice S. Whittemore, PhD, Valerie McGuire, PhD, Weiva Sieh, MD, PhD, Ulf Kristoffersson, MD, PhD, Håkan Olsson, MD, PhD, Åke Borg, PhD, Douglas A. Levine, MD, Linda Steele, BS, Mary S. Beattie, MD, MAS, Salina Chan, BSc, Robert L. Nussbaum, MD, Kirsten B. Moysich, PhD, Jenny Gross, MPH, Ilana Cass, MD, Christine Walsh, MD, Andrew J. Li, MD, Ronald Leuchter, MD, Ora Gordon, MD, MS, Montserrat Garcia-Closas, MD, DrPH, Simon A. Gayther, PhD, Stephen J. Chanock, MD, Antonis C. Antoniou, PhD, Paul D. P. Pharoah, BM, BCh, PhD, for the EMBRACE, kConFab Investigators, and The Cancer Genome Atlas Research Network GERMLINE MUTATIONS IN THE tumor suppressor genes BRCA1 (NCBI Entrez Gene 672) and BRCA2 (NCBI Entrez Gene 675) are the strongest known genetic risk factors for both breast and epithelial ovarian cancer (EOC) and are found in 6% to 15% of women with EOC. BRCA1 is involved in DNA repair, cell-cycle checkpoint control, chromatin remodeling, transcriptional regulation, and mitosis, and BRCA2 has an important role in homologous recombination. The clinical characteristics of EOCs among BRCA1/2 carriers differ from that of noncarriers. BRCA1-related disease is more likely to be of serous histology, high grade, and advanced stage. Less data are available for BRCA2-related EOC due to their lower prevalence and lower EOC penetrance relative to BRCA1, but a similar pattern is generally reported. The relative prognosis of BRCA1/2 carriers and noncarriers is unclear. A