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 46,355 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.