Oral contraceptives and breast cancer: review of the epidemiologic literature

Abstract

Oral contraceptives have caused little or no overall increase in risk of breast cancer in women in developed countries, even in long-term users or after more than two decades since initial exposure. Limited evidence suggests a possible small increase in risk in users of oral contraceptives in developing countries, and further studies of breast cancer and oral contraceptives in low risk populations are warranted. Oral contraceptives may enhance risk of breast cancer in young women with a history of benign breast disease, and this possibility should also be investigated further. Multiple investigations have fairly consistently shown risk of breast cancer in women under age 45 years to be increased slightly in long-term users of oral contraceptives. Further studies should be conducted to elucidate the mechanism of this apparent phenomenon.

PIP: All reports of case-control and cohort studies of breast cancer and oral contraceptives (OC) were reviewed, estimated relative risks were summarized in 28 tables, and where possible, summary relative risks with 95% confidence limits and chi-square tests for heterogeneity were computed, for various categories of women. The categories were: case control and cohort, all ages combined; long-term users, case control, and cohort, all ages; 10-20 years after initial use, case control, and cohort, women of all ages; women in developing countries, case-control; by socioeconomic status; nulliparous; before 1st birth; by parity; by body mass index; with or without benign breast disease before or after diagnosis of benign breast disease; by duration of use before 1st pregnancy, case-control and cohort, after various latent period; before age 25, case-control; under age 45, case control, cohort, for long duration; by age at diagnosis; used OC near menopause; by type of formulation. OC use gave no increase in risk to women of all ages combined even after 2 decades of use. In low-risk populations, as in developing countries and in Seventh Day Adventists, OC use heightened risk about 21% but no particular risk factors stand out in detailed studies in developed countries. More work needs to be done to pinpoint the timing and type of benign lesion found to be associated with higher risk, only found in younger women. Similarly, more detailed studies with a pathology component should be done to find out what type of cells, ductal or lobular, and whether pre-existing tumors or new tumors, are involved in the inconsistent finding of increased risk in users under 25 before childbearing, and the more consistent heightened risk of 42% in users under 45 with long duration of use (10-20 years). So far there is no evidence of a screening bias. Further examination is also indicated of the possible higher risk for peri-menopausal women, and more data is needed on the relationship of medroxy-progesterone acetate to breast cancer.