Hormone replacement therapy and the risk of breast cancer. Nested case-control study in a cohort of Swedish women attending mammography screening.

There is concern that hormone replacement therapy (HRT) increases the risk of breast cancer. We undertook a case-control study of this risk relationship within a cohort of 40- to 74-year-old women in Uppsala County, Sweden, who participated in mammography screening. Incident cases of breast cancer were ascertained during 5 years of follow-up. In all, 435 cases (87% invasive, 13% in situ cancers) were detected, 313 through screening and 122 through clinical diagnosis. As controls, 1,740 women were selected randomly. Information on risk factors and use of HRT was obtained through interviews before the start of follow-up. Multivariate analyses revealed an increased risk among users of any type of HRT for more than 10 years, the odds ratio (OR) being 2.1 (95% confidence interval [CI] 1.1-4.0), as well as when restricting analyses to cases diagnosed through mammography screening. After stratification for compound type, risk estimates were apparently higher among women reporting estradiol-progestin combined treatment vs. estradiol or conjugated estrogens alone, with ORs for more than 10 years of intake being 2.4 (95% CI 0.7-8.6) and 1.3 (95% CI 0.5-3.7), respectively. Analyses through a model including both compound type and length of hormone intake confirmed a significant excess risk linked to treatment for more than 10 years, OR = 2.6 (95% CI 1.3-5.1). Our results indicate a moderately increased risk of breast cancer after many years of HRT and, hypothetically, a further enhancement of the risk with added progestins.