Menopausal Estrogen and Estrogen-progestin Replacement Therapy and Breast Cancer Risk

Context: Whether menopausal hormone replacement therapy using a combined estrogen-progestin regimen increases risk of breast cancer beyond that associated with estrogen alone is unknown.

Objective: To determine whether increases in risk associated with the estrogen-progestin regimen are greater than those associated with estrogen alone.

Design: Cohort study of follow-up data for 1980-1995 from the Breast Cancer Detection Demonstration Project, a nationwide breast cancer screening program.

Setting: Twenty-nine screening centers throughout the United States.

Participants: A total of 46355 postmenopausal women (mean age at start of follow-up, 58 years).

Main Outcome Measure: Incident breast cancers by recency, duration, and type of hormone use.

Results: During follow-up, 2082 cases of breast cancer were identified. Increases in risk with estrogen only and estrogen-progestin only were restricted to use within the previous 4 years (relative risk [RR], 1.2 [95% confidence interval [CI], 1.0-1.4] and 1.4 [95% CI, 1.1-1.8], respectively); the relative risk increased by 0.01 (95% CI, 0.002-0.03) with each year of estrogen-only use and by 0.08 (95% CI, 0.02-0.16) with each year of estrogen-progestin-only use among recent users, after adjustment for mammographic screening, age at menopause, body mass index (BMI), education, and age. The P value associated with the test of homogeneity of these estimates was .02. Among women with a BMI of 24.4 kg/m2 or less, increases in RR with each year of estrogen-only use and estrogen-progestin-only use among recent users were 0.03 (95% CI, 0.01-0.06) and 0.12 (95% CI, 0.02-0.25), respectively. These associations were evident for the majority of invasive tumors with ductal histology and regardless of extent of invasive disease. Risk in heavier women did not increase with use of estrogen only or estrogen-progestin only.

Conclusion: Our data suggest that the estrogen-progestin regimen increases breast cancer risk beyond that associated with estrogen alone.