A nested case-control study of hormone replacement therapy in relation to breast cancer

Based on the observed findings that breast cancer risk is associated with ages at menarche and menopause, which suggests an important role for hormones, the concern regarding hormone replacement therapy has been raised. Studies of the relationship between either estrogen or combined estrogen plus progestin therapy and the risk of breast have been inconclusive, in particular, studies of long term use of combined therapy are limited because combined therapy did not become common until the 1980's. A nested case-control study was conducted among postmenopausal female enrollees of Group Health Cooperative of Puget Sound (GHC). 705 breast cancer cases aged 50--74 years old who were newly diagnosed with first primary invasive breast cancer during the period July 1, 1990 through December 31,1995 were identified. 692 control subjects, frequency matched to cases by year of diagnosis, age at diagnosis and years of GHC enrollment were randomly selected from the enrollment files of GHC members during the years the cases were diagnosed. Exposure status was determined from the computerized pharmacy records of GHC. Information about potential confounders and effect modifiers was gathered through questionnaire. Compared to never users, current use (use during the six month period prior to the reference date) of estrogen pills and of progestin pills was associated with a higher risk of breast cancer (OR = 1.30, 95% CI = 1.01--1.69 for estrogen pills and OR = 1.51,95% CI = 1.09--2.08 for progestin pills) after adjustment for age, year of diagnosis and number of prior mammograms. Long term use of estrogen with or without progestin was associated with a two-fold increase in the risk of breast cancer (OR = 2.36, 95% CI = 1.55--3.61 for more than 1862.5 pills, which was equivalent to 74.5 months of use assuming 25 pills a month). We are also able to demonstrate a positive trend for estrogen use (p = 0.000 for cumulative pill counts and p = 0.001 for dosage in recent ten-year analysis). Our results confirmed the previous findings that current use of estrogen alone or estrogen plus progestin was associated with a moderately increased risk of breast cancer. This increased risk was largely due to estrogen, but not progestin.