Tamar Perri1, Dror Lifshitz2, Siegal Sadetzki3, Bernice Oberman4, Dror Meirow5, Gilad Ben-Baruch2, Eitan Friedman6, Jacob Korach2. 1. Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: tamarperri@gmail.com. 2. Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 3. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Cancer and Radiation Epidemiology Unit, Gertner Institute, Sheba Medical Center, Tel Hashomer, Israel. 4. Cancer and Radiation Epidemiology Unit, Gertner Institute, Sheba Medical Center, Tel Hashomer, Israel. 5. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Fertility Preservation Center and IVF Unit, Sheba Medical Center, Tel Hashomer, Israel. 6. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Susanne Levy-Gertner Oncogenetics Unit, Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel.
Abstract
OBJECTIVE: To determine whether BRCA mutation carriers who undergo fertility treatments are at increased risk of developing invasive epithelial ovarian cancer (IEOC). DESIGN: Historical cohort study. SETTING: Tertiary university-affiliated medical center and the National Cancer Registry. PATIENT(S): A total of 1,073 Jewish Israeli BRCA mutation carriers diagnosed in a single institution between 1995 and 2013, including 164 carriers (15.2%) who had fertility treatments that included clomiphene citrate (n = 82), gonadotropin (n = 69), in vitro fertilization (IVF) (n = 66), or a combination (n = 50), and 909 carriers not treated for infertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Odds ratios (OR) and 95% confidence intervals (CI) for IEOC association with fertility treatments and other hormone and reproductive variables. RESULT(S): In 175 (16.3%) mutation carriers, IEOC was diagnosed; 139 women carried BRCA1, 33 carried BRCA2, and 3 had unknown mutations. Fertility treatments were not associated with IEOC risk (age-adjusted OR 0.63; 95% CI, 0.38-1.05) regardless of treatment type (with clomiphene citrate, OR 0.87; 95% CI, 0.46-1.63; with gonadotropin, OR 0.59; 95% CI, 0.26-1.31; with IVF, OR 1.08, 95% CI, 0.57-2.06). Multivariate analysis indicated an increased risk of IEOC with hormone-replacement therapy (OR 2.22; 95% CI, 1.33-3.69) and a reduced risk with oral contraceptives (OR 0.19; 95% CI, 0.13-0.28) in both BRCA1 and BRCA2 mutation carriers. Parity was a risk factor for IEOC by univariate but not multivariate analysis. CONCLUSION(S): According to our results, treatments for infertile BRCA mutation carriers should not be contraindicated or viewed as risk modifiers for IEOC. Parity as a risk factor in BRCA mutation carriers warrants further investigation.
OBJECTIVE: To determine whether BRCA mutation carriers who undergo fertility treatments are at increased risk of developing invasive epithelial ovarian cancer (IEOC). DESIGN: Historical cohort study. SETTING: Tertiary university-affiliated medical center and the National Cancer Registry. PATIENT(S): A total of 1,073 Jewish Israeli BRCA mutation carriers diagnosed in a single institution between 1995 and 2013, including 164 carriers (15.2%) who had fertility treatments that included clomiphene citrate (n = 82), gonadotropin (n = 69), in vitro fertilization (IVF) (n = 66), or a combination (n = 50), and 909 carriers not treated for infertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Odds ratios (OR) and 95% confidence intervals (CI) for IEOC association with fertility treatments and other hormone and reproductive variables. RESULT(S): In 175 (16.3%) mutation carriers, IEOC was diagnosed; 139 women carried BRCA1, 33 carried BRCA2, and 3 had unknown mutations. Fertility treatments were not associated with IEOC risk (age-adjusted OR 0.63; 95% CI, 0.38-1.05) regardless of treatment type (with clomiphene citrate, OR 0.87; 95% CI, 0.46-1.63; with gonadotropin, OR 0.59; 95% CI, 0.26-1.31; with IVF, OR 1.08, 95% CI, 0.57-2.06). Multivariate analysis indicated an increased risk of IEOC with hormone-replacement therapy (OR 2.22; 95% CI, 1.33-3.69) and a reduced risk with oral contraceptives (OR 0.19; 95% CI, 0.13-0.28) in both BRCA1 and BRCA2 mutation carriers. Parity was a risk factor for IEOC by univariate but not multivariate analysis. CONCLUSION(S): According to our results, treatments for infertile BRCA mutation carriers should not be contraindicated or viewed as risk modifiers for IEOC. Parity as a risk factor in BRCA mutation carriers warrants further investigation.
Authors: Yang Liu; Lan Ma; Xiaoling Yang; Jia Bie; Dongya Li; Chunyi Sun; Jie Zhang; Yushi Meng; Jie Lin Journal: Front Endocrinol (Lausanne) Date: 2019-12-03 Impact factor: 5.555