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Grand Rounds

Is Duration of Oral Contraceptive Use in Women with BRCA Mutations Linked to Reduction of Ovarian Cancer Risk?

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BACKGROUND AND PURPOSE:

  • Schrijver et al. (AJOG, 2021) investigated, in detail, the associations of various characteristics of oral contraceptive use and risk of ovarian cancer in BCRA mutation carriers

METHODS:

  • International retrospective study
  • Participants
    • BRCA1/2 mutation carriers
  • Exposures
    • Oral contraceptive use
  • Study design
    • Age-dependent–weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate
    • Analyses were left truncated at 5 years before baseline questionnaire, in order to minimize survival bias
    • Analysis of duration of oral contraceptive use was stratified by recency of use
    • Multivariate analyses covariates included: Duration of use | Age at first use | Time since last use | Duration of oral contraceptive use
  • Primary outcome
    • Ovarian cancer

RESULTS:

  • 3989 BRCA1/2 carriers
  • Mutation carriers who were diagnosed with ovarian cancer used oral contraceptives less often than unaffected carriers
    • Ever use in diagnosed patients
      • BRCA1: 58.6%
      • BRCA2: 53.5%
    • Ever use in unaffected patients
      • BRCA1: 88.9%
      • BRCA2: 80.7%
  • Median duration of use
    • Diagnosed patients
      • BRCA1: 7 years
      • BRCA2: 7 years
    • Unaffected patients
      • BRCA1: 9 years
      • BRCA2: 8 years
  • In univariate analyses, the following were associated with a reduction in the risk of ovarian cancer
    • A longer duration of oral contraceptive use
    • More recent oral contraceptive use
  • In multivariate analyses, duration of oral contraceptive use was a prominent protective factor
    • 5 to 9 years vs <5 years: Hazard ratio (HR) 0.67 (95% CI, 0.40 to 1.12)
    • >10 years vs <5 years: HR 0.37 (95% CI, 0.19 to 0.73); Ptrend = 0.008
  • The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years for long-term users (duration of ≥10 years)
    • BRCA1 <15 years since last use: HR 0.24 (95% CI 0.14 to 0.43)
    • BRCA1 >15 years since last use: HR 0.56 (95% CI 0.18 to 0.59)
  • Univariate results for BRCA2 mutation carriers were similar but were inconclusive because of limited sample size

CONCLUSION:

  • For women who are BRCA1 mutation carriers, longer duration of oral contraceptive use is associated with a reduced risk of ovarian cancer
    • The protective benefit of oral contraceptive use is long-term
  • Effect may be similar for BRCA2, but conclusions were limited due to smaller sample size
  • Limitations included lack of data regarding specific oral contraceptive formulations
  • The authors comment on the associated risk of oral contraceptives and breast cancer and conclude

The inverse association with ovarian cancer is stronger than the possible positive association with breast cancer risk

Learn More – Primary Sources:

Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers: an international cohort study

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Related ObG Topics:

Long-Term Oral Contraceptive Use and Cancer Risk
ACOG Practice Advisory: Counseling Patients About Breast Cancer Risk and Hormonal Contraception
Do Contraceptives Decrease Risk for All Ovarian Cancers?
Is IUD Use Associated with a Reduced Risk of Ovarian Cancer?

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