Background: Breast cancer is the leading cause of cancer death in U.S. women 20 to 59 years of age and is the most common cause of cancer in women worldwide. Despite growing evidence that oral contraceptive (OC) use may be associated with an increased risk of breast cancer, only one out of 15 studies conducted before 1980 showed this association. However, these earlier studies may not have allowed adequate follow-up. Divergent study results also may be attributed to the growing societal trend for women to start OC use earlier and to use them for longer periods of time.

The Study: Kahlenborn and colleagues evaluated whether OC use was associated with an increased risk of breast cancer in premenopausal women. The meta-analysis included 34 case-control studies of breast cancer and OC use that were published in or after 1980. The review included 18,406 participants in the case group and 27,677 participants in the control group. Inclusion criteria were age younger than 50 years or documentation of being premenopausal. Several scenarios were examined, including nulliparous and parous women who had ever used OCs. Parous women were divided into groups who had used OCs before or after their first full-term pregnancy.

Results: The overall odds ratio (OR) for developing premenopausal breast cancer among women who had ever used OCs was 1.19. Nulliparous women who had ever used OCs had an OR of 1.24, and parous women who had ever used OCs had a similar OR of 1.29. This increased to 1.52 for women who used OCs for four or more years before their first full-term pregnancy (see accompanying table).

Conclusion: The authors conclude that OC use is associated with an increased risk of breast cancer in premenopausal women, especially when used for prolonged periods of time before their first full-term pregnancy. This risk appears to be greatest in women who had used OCs for more than four years before their first full-term pregnancy, although the reason remains unclear. The authors express concern that the ORs may be underestimations because of the potential for survivor bias in the studies they reviewed.

editor's note: The Kahlenborn study is a meta-analysis, a type of study that generally relies on previously published results and may have difficulty adjusting for factors not addressed directly in the original studies. For instance, this study was unable to evaluate whether the increased risk of breast cancer might decrease to baseline risk after OC use is discontinued, which has been reported in a larger pooled analysis study.¹

Although other studies have also reported an association between OC use and breast cancer risk, the relative risk remains very small. It has been estimated that the number of additional instances of breast cancer diagnosed within 10 years of OC use may be up to 4.7 per 10,000 patients. However, the wider risks and benefits of OC use must be considered before initiating or continuing them. Other significant noncancer risks of OC use include venous thromboembolism, ischemic stroke, and myocardial infarction. On the other hand, OC use can improve symptoms from ovarian cysts, preserve bone mineral density, relieve menstrual disorders, and decrease the risk of ovarian and endo-metrial cancers.

These results emphasize the importance of a thorough evaluation of female patients considering OC use, including a frank discussion with the patient and weighing the risks and benefits of OC use based on the individual patient. Regular follow-up, including annual clinical breast examinations, remains a vital component of ongoing treatment in patients using OCs.—k.t.m.