Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Fertil Steril. 2015 May;103(5):1305-12. doi: 10.1016/j.fertnstert.2015.02.011. Epub 2015 Mar 16.
To determine whether BRCA mutation carriers who undergo fertility treatments are at increased risk of developing invasive epithelial ovarian cancer (IEOC).
Historical cohort study.
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.
确定接受生育治疗的 BRCA 基因突变携带者是否会增加罹患浸润性上皮性卵巢癌（IEOC）的风险。
历史队列研究。
三级大学附属医疗中心和国家癌症登记处。
总共纳入 1073 名在 1995 年至 2013 年期间在一家机构确诊的以色列裔犹太 BRCA 基因突变携带者，其中 164 名携带者（15.2%）接受了包括枸橼酸氯米酚（n=82）、促性腺激素（n=69）、体外受精（IVF）（n=66）或联合治疗（n=50）在内的生育治疗，909 名携带者未接受不孕治疗。
无。
IEOC 与生育治疗以及其他激素和生殖变量之间的比值比（OR）和 95%置信区间（CI）。
在 175 名（16.3%）突变携带者中诊断出 IEOC，139 名女性携带 BRCA1 基因突变，33 名携带 BRCA2 基因突变，3 名携带未知突变。无论治疗类型如何，生育治疗均与 IEOC 风险无关（年龄调整 OR 0.63；95%CI，0.38-1.05）（枸橼酸氯米酚治疗，OR 0.87；95%CI，0.46-1.63；促性腺激素治疗，OR 0.59；95%CI，0.26-1.31；IVF 治疗，OR 1.08，95%CI，0.57-2.06）。多变量分析表明，激素替代疗法（OR 2.22；95%CI，1.33-3.69）会增加 BRCA1 和 BRCA2 突变携带者罹患 IEOC 的风险，而口服避孕药（OR 0.19；95%CI，0.13-0.28）则会降低风险。产次是 BRCA 突变携带者罹患 IEOC 的单变量危险因素，但不是多变量危险因素。
根据我们的结果，不应为生育治疗的 BRCA 基因突变携带者禁忌或视为 IEOC 的风险修饰因素。BRCA 基因突变携带者中，产次是一个危险因素，需要进一步研究。
