PURPOSE: To evaluate the long-term survival of ovarian cancer (OvC) patients in total and by BRCA1/2 mutation status. PATIENTS AND METHODS: In a nationwide case-control study on OvC conducted in Israel between 1994 and 1999, 779 Jewish women with epithelial invasive OvC were tested for the three Ashkenazi Jewish founder mutations in BRCA1 (185delAG; 5382insC) and BRCA2 (6174delT) genes and followed for survival up to 2003. Of the 605 women of Ashkenazi origin, 213 (35.2%) carried a mutation in the BRCA1/2 genes. Clinical characteristics were abstracted from the patients' medical records. The Kaplan-Meier method, log-rank tests, and stepwise Cox regression model were used for survival analyses. RESULTS: The 5-year survival rate for the entire group was 39%. Median survival for carriers was significantly longer than for noncarriers (53.7 v 37.9 months, respectively; P = .002). This differential survival was pronounced among women diagnosed at stages III to IV (5-year survival rates of 38.1% and 24.5% for carriers and noncarriers, respectively; P < .001) and for women with poor grade (45.4% v 31.5%, for carriers and noncarriers, respectively; P < .001). These results remained significant after controlling for age at diagnosis, grade, and morphology. This benefit in prognosis was seen for both BRCA1 and BRCA2 carriers compared with noncarriers. During the study period (median follow-up, 6.2 years), being a BRCA1/2 mutation carrier decreased the mortality rate by 28%. CONCLUSION: This study confirms that, among Ashkenazi OvC patients, BRCA1/2 mutations are associated with improved long-term survival. This may be due to distinct clinical behavior and/or to a better response to chemotherapy.
PURPOSE: To evaluate the long-term survival of ovarian cancer (OvC) patients in total and by BRCA1/2 mutation status. PATIENTS AND METHODS: In a nationwide case-control study on OvC conducted in Israel between 1994 and 1999, 779 Jewish women with epithelial invasive OvC were tested for the three Ashkenazi Jewish founder mutations in BRCA1 (185delAG; 5382insC) and BRCA2 (6174delT) genes and followed for survival up to 2003. Of the 605 women of Ashkenazi origin, 213 (35.2%) carried a mutation in the BRCA1/2 genes. Clinical characteristics were abstracted from the patients' medical records. The Kaplan-Meier method, log-rank tests, and stepwise Cox regression model were used for survival analyses. RESULTS: The 5-year survival rate for the entire group was 39%. Median survival for carriers was significantly longer than for noncarriers (53.7 v 37.9 months, respectively; P = .002). This differential survival was pronounced among women diagnosed at stages III to IV (5-year survival rates of 38.1% and 24.5% for carriers and noncarriers, respectively; P < .001) and for women with poor grade (45.4% v 31.5%, for carriers and noncarriers, respectively; P < .001). These results remained significant after controlling for age at diagnosis, grade, and morphology. This benefit in prognosis was seen for both BRCA1 and BRCA2 carriers compared with noncarriers. During the study period (median follow-up, 6.2 years), being a BRCA1/2 mutation carrier decreased the mortality rate by 28%. CONCLUSION: This study confirms that, among Ashkenazi OvC patients, BRCA1/2 mutations are associated with improved long-term survival. This may be due to distinct clinical behavior and/or to a better response to chemotherapy.
Authors: Francisco J Candido-dos-Reis; Honglin Song; Ellen L Goode; Julie M Cunningham; Brooke L Fridley; Melissa C Larson; Kathryn Alsop; Ed Dicks; Patricia Harrington; Susan J Ramus; Anna de Fazio; Gillian Mitchell; Sian Fereday; Kelly L Bolton; Charlie Gourley; Caroline Michie; Beth Karlan; Jenny Lester; Christine Walsh; Ilana Cass; Håkan Olsson; Martin Gore; Javier J Benitez; Maria J Garcia; Irene Andrulis; Anna Marie Mulligan; Gord Glendon; Ignacio Blanco; Conxi Lazaro; Alice S Whittemore; Valerie McGuire; Weiva Sieh; Marco Montagna; Elisa Alducci; Siegal Sadetzki; Angela Chetrit; Ava Kwong; Susanne K Kjaer; Allan Jensen; Estrid Høgdall; Susan Neuhausen; Robert Nussbaum; Mary Daly; Mark H Greene; Phuong L Mai; Jennifer T Loud; Kirsten Moysich; Amanda E Toland; Diether Lambrechts; Steve Ellis; Debra Frost; James D Brenton; Marc Tischkowitz; Douglas F Easton; Antonis Antoniou; Georgia Chenevix-Trench; Simon A Gayther; David Bowtell; Paul D P Pharoah Journal: Clin Cancer Res Date: 2014-11-14 Impact factor: 12.531
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Authors: Joyce Liu; Mihaela C Cristea; Paul Frankel; Susan L Neuhausen; Linda Steele; Verena Engelstaedter; Ursula Matulonis; Sharon Sand; Nadine Tung; Judy E Garber; Jeffrey N Weitzel Journal: Cancer Genet Date: 2012 Jan-Feb
Authors: Tom Walsh; Silvia Casadei; Ming K Lee; Christopher C Pennil; Alex S Nord; Anne M Thornton; Wendy Roeb; Kathy J Agnew; Sunday M Stray; Anneka Wickramanayake; Barbara Norquist; Kathryn P Pennington; Rochelle L Garcia; Mary-Claire King; Elizabeth M Swisher Journal: Proc Natl Acad Sci U S A Date: 2011-10-17 Impact factor: 11.205
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