Joanne Kotsopoulos1, Barry Rosen2, Isabel Fan3, Joel Moody3, John R McLaughlin4, Harvey Risch5, Taymaa May2, Ping Sun6, Steven A Narod7. 1. Women's College Research Institute, Women's College Hospital, 790 Bay Street, 7th Floor, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, 155 College Street, Health Science Building, 6th Floor, Toronto, ON, Canada. Electronic address: steven.narod@wchospital.ca. 2. Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON, Canada; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Toronto, Main Floor Room 719, 610 University Ave, Toronto, ON, Canada. 3. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, 600 University Avenue, Toronto, ON, Canada. 4. Public Health Ontario, Toronto, ON, Canada. 5. Department of Chronic Disease Epidemiology, Yale School of Public Health, 60 College St., New Haven, CT, USA. 6. Women's College Research Institute, Women's College Hospital, 790 Bay Street, 7th Floor, Toronto, ON, Canada. 7. Women's College Research Institute, Women's College Hospital, 790 Bay Street, 7th Floor, Toronto, ON, Canada; Dalla Lana School of Public Health, University of Toronto, 155 College Street, Health Science Building, 6th Floor, Toronto, ON, Canada.
Abstract
OBJECTIVES: After a diagnosis of ovarian cancer, positive BRCA mutation status confers a transient mortality benefit that diminishes with time. The majority of women who survive for 10-12 years are effectively cured of their disease. Thus, it is important to estimate the probability of long-term survival by BRCA mutation status and treatment-related factors. METHODS: We included unselected epithelial ovarian cancers diagnosed in Ontario, Canada from 1995 to 1999 and from 2002 to 2004. Clinical information was obtained from medical records. Survival status was determined by linkage to the Ontario Cancer Registry. We estimated the annual mortality for these patients. We compared women who did and did not survive 10 years for a range of factors including BRCA mutation status and extent of residual disease post-surgery. RESULTS: Of the 1421 patients, 109 (7.7%) had BRCA1 mutations and 68 (4.8%) had BRCA2 mutations. A status of no residual disease was achieved by 39% of non-carriers and 19% of mutation carriers (P<0.0001). By 10-years of follow-up, 43% of non-carriers, 57% of BRCA1 mutation carriers and 69% of BRCA2 mutation carriers had died from ovarian cancer. Among women with stage III/IV serous cancers and no residual disease, the 10-year actuarial survival was 42% for non-carriers and 29% for mutation carriers (P=0.40). CONCLUSION: The initial survival advantage among women with BRCA mutations may reflect a higher initial sensitivity of BRCA carriers to chemotherapy, but this response does not predict long-term survival. The strongest predictor of long-term survival is status of no residual disease at resection.
OBJECTIVES: After a diagnosis of ovarian cancer, positive BRCA mutation status confers a transient mortality benefit that diminishes with time. The majority of women who survive for 10-12 years are effectively cured of their disease. Thus, it is important to estimate the probability of long-term survival by BRCA mutation status and treatment-related factors. METHODS: We included unselected epithelial ovarian cancers diagnosed in Ontario, Canada from 1995 to 1999 and from 2002 to 2004. Clinical information was obtained from medical records. Survival status was determined by linkage to the Ontario Cancer Registry. We estimated the annual mortality for these patients. We compared women who did and did not survive 10 years for a range of factors including BRCA mutation status and extent of residual disease post-surgery. RESULTS: Of the 1421 patients, 109 (7.7%) had BRCA1 mutations and 68 (4.8%) had BRCA2 mutations. A status of no residual disease was achieved by 39% of non-carriers and 19% of mutation carriers (P<0.0001). By 10-years of follow-up, 43% of non-carriers, 57% of BRCA1 mutation carriers and 69% of BRCA2 mutation carriers had died from ovarian cancer. Among women with stage III/IV serous cancers and no residual disease, the 10-year actuarial survival was 42% for non-carriers and 29% for mutation carriers (P=0.40). CONCLUSION: The initial survival advantage among women with BRCA mutations may reflect a higher initial sensitivity of BRCA carriers to chemotherapy, but this response does not predict long-term survival. The strongest predictor of long-term survival is status of no residual disease at resection.
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