Clinical Inquiries

Do oral contraceptives put women with a family history of breast cancer at increased risk?

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EVIDENCE-BASED ANSWER:

No. Modern combined oral contraceptive pills (OCPs) don’t increase breast cancer risk in women with a family history (strength of recommendation [SOR]: B, systematic review of cohort, case-control studies). However, older, higher-dose OCPs (in use before 1975) did increase breast cancer risk in these women (SOR: C, case-control study).

Similarly, modern OCPs don’t raise breast cancer risk in women with BRCA1/2 mutations, although higher-dose, pre-1975 OCPs did (SOR: B and C, a meta-analysis of cohort and case-control studies).

EVIDENCE SUMMARY

A systematic review of the effect of combined OCPs on women with a family history of breast cancer found no additional increase in risk.1 Investigators identified 3 retrospective cohort studies (N=66,500, with 8500 cases) and 7 case-control studies (total 10,500 cases) from the past 40 years, most including women from the United States and Canada, but one including women from 5 continents.

In most trials, women of reproductive age using combined OCPs had 1 or more first-degree female relatives with breast cancer, although a few trials also included second-degree relatives. Women ranged in age from 20 to 79 years at diagnosis, and most trials controlled for age, parity, menstrual and menopausal history, duration of OCP exposure, and age at first use. Follow-up intervals for the retrospective cohort studies ranged from 5 to 16 years. Investigators were unable to combine results because of heterogenous populations.

Three of the cohort studies found no significant difference in breast cancer risk between OCP users and nonusers, regardless of age or duration of use. One cohort study found an increased risk in women taking older, higher-dose OCPs from before 1975 (relative risk [RR]=3.3; 95% confidence interval [CI], 1.5-7.2). All of the case-control studies found no significant difference in breast cancer risk for any age of starting, duration of OCP use, or degree of relative with breast cancer.

A meta-analysis of 54 case-control studies (6757 cases), comprising approximately 90% of the epidemiologic information on this topic, also found no significant difference in breast cancer risk related to OCP use among women with one or more first-degree relatives with breast cancer.2 Investigators found that neither recent OCP use (<10 years, RR=0.77; 95% CI, 0.54-1.11) nor past OCP use (>10 years, RR=1.01; 95% CI, 0.80-1.28) affected risk of developing breast cancer.

Three additional case-control studies involving women with a family history of breast cancer also found no significant association for breast cancer incidence among OCP users compared with nonusers.3-5

Evidence-based answers from the Family Physicians Inquiries Network

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