Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk

Context Whether menopausal hormone replacement therapy using a combined est rogen-progestin regimen increases risk of breast cancer beyond that associa ted with estrogen alone is unknown. Objective To determine whether increases in risk associated with the estrog en-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 progr am. Setting Twenty-nine screening centers throughout the United States. Participants A total of 46 355 postmenopausal women (mean age at start of f ollowup, 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. Incr eases in risk with estrogen only and estrogen-progestin only were restricte d to use within the previous 4 years (relative risk [RR], 1.2 [95% confiden ce interval {CI}, 1.0-1.4] and 1.4 [95% CI, 1.1-1.8], respectively); the re lative risk increased by 0.01 (95% CI, 0.002-0.03) with each year of estrog en-only use and by 0.08 (95% CI, 0.02-0.16) with each year of estrogen-prog estin-only use among recent users, after adjustment for mammographic screen ing, age at menopause, body mass index (BMI), education, and age. The P val ue associated with the test of homogeneity of these estimates was .02. Amon g women with a BMI of 24.4 kg/m(2) or less, increases in RR with each year of estrogen-only use and estrogen-progestin-only use among recent users wer e 0.03 (95% CI, 0.01-0.06) and 0.12 (95% CI, 0.02-0.25), respectively. Thes e associations were evident for the majority of invasive tumors with ductal histology and regardless of extent of invasive disease. Risk in heavier wo men did not increase with use of estrogen only or estrogen-progestin only. Conclusion Our data suggest that the estrogen-progestin regimen increases b reast cancer risk beyond that associated with estrogen alone.