Oral contraceptives and the risk of hereditary ovarian cancer

Narod SA, Risch H, Moslehi R, Dorum A, Neuhausen S, Olsson H, ProvencherD, Radice P, Evans G, Bishop S, Brunet JS, Ponder BAJ
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2001

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Reviewers: John Han-Chih Chang, MD and Kenneth Blank, MD
Source: New England Journal of Medicine 339 (7): 424

Introduction

Women with mutations to the BRCA1 or 2 genes are at increased risk forthe development of breast and ovarian cancer. The estimated lifetimerisk of ovarian cancer in women with BRCA1 mutations is 45% and in womenwith BRCA2 mutations 25%. Women with a strong family history of ovariancancer and those with proven mutations to the BRCA genes propose achallenging clinical dilemma. Most gynecologic oncologists offertreatment in the form of diligent screening with ultrasound and bloodwork, although the efficacy of this regimen is not known. Somegynecologic oncologists offer bilateral oophorectomy (removal of bothovaries). This procedure is done on an outpatient basis and carrieslittle morbidity, with the obvious exception that the patient isrendered sterile.

Another option that has become popular is the use of oralcontraceptives. Oral contraceptives are known to protect against thedevelopment of ovarian cancer. The estimated risk reduction inunselected women taking oral contraception is 50% or more. The mechanismof protection is unclear but likely due to the stopping of ovulation.The Hereditary Ovarian Cancer Study Group undertook a study to determineif oral contraceptives are effective at reducing the rate of ovariancancer in selected patients with mutations to BRCA1 or BRCA2.

Materials and MethodsP>The study enrolled 207 patients with hereditary ovarian cancer and aBRCA1 mutation (179 patients) or a BRCA2 mutation (28 women). Ascontrols, 161 sisters who were free of ovarian cancer were alsoenrolled. The investigators then performed a retrospective review oforal contraception use in the two groups. Information was obtained bywritten questionnaire or verbal interview and was compared between thetwo groups.

Results

After adjusting for year of birth and parity, the investigators founduse of oral contraceptives significantly reduces the risk of developingovarian cancer. The protection afforded by oral contraception use wasapproximately 50% and rose with increasing years of usage.

Discussion and Conclusion

The study can be criticized on several counts, including the bias thatmay be inherent in any retrospective review. Additionally, the authorspoint out that ideally the 'sister' group would all have BRCA mutations.Notwithstanding these limitations, the study provides evidence that oralcontraception protects women with BRCA mutations from ovarian cancer.