title: Fertility treatments and invasive epithelial ovarian cancer risk in Jewish Israeli BRCA1 or BRCA2 mutation carriers.
abstract: OBJECTIVE
  To determine whether BRCA mutation carriers who undergo fertility treatments are at increased risk of developing invasive epithelial ovarian cancer (IEOC).
  
  
  METHODS
  Historical cohort study.
  
  
  METHODS
  Tertiary university-affiliated medical center and the National Cancer Registry.
  
  
  METHODS
  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.
  
  
  METHODS
  None.
  
  
  METHODS
  Odds ratios (OR) and 95% confidence intervals (CI) for IEOC association with fertility treatments and other hormone and reproductive variables.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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: 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.
authors: Tamar
authors: T
authors: Perri
authors: Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Dror
authors: D
authors: Lifshitz
authors: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Cancer and Radiation Epidemiology Unit, Gertner Institute, Sheba Medical Center, Tel Hashomer, Israel.
authors: Siegal
authors: S
authors: Sadetzki
authors: Cancer and Radiation Epidemiology Unit, Gertner Institute, Sheba Medical Center, Tel Hashomer, Israel.
authors: Bernice
authors: B
authors: Oberman
authors: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Fertility Preservation Center and IVF Unit, Sheba Medical Center, Tel Hashomer, Israel.
authors: Dror
authors: D
authors: Meirow
authors: Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Gilad
authors: G
authors: Ben-Baruch
authors: 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.
authors: Eitan
authors: E
authors: Friedman
authors: Department of Gynecologic Oncology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Jacob
authors: J
authors: Korach
mesh_terms: D000046:Academic Medical Centers; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006579:Heterozygote; D006801:Humans; D007246:Infertility / Q000503:physiopathology / Q000628:therapy*; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009361:Neoplasm Invasiveness; D009375:Neoplasms, Glandular and Epithelial / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D010298:Parity; D010641:Phenotype; D011446:Prospective Studies; D012042:Registries; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects*; D018570:Risk Assessment; D012307:Risk Factors; D062606:Tertiary Care Centers; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
keywords: BRCA mutations; cancer risk; fertility treatment; ovarian cancer