Context The Women's Health Initiative trial of combined estrogen plus progestin
was stopped early when overall health risks, including invasive breast cancer,
exceeded benefits. Outstanding issues not previously addressed include characteristics
of breast cancers observed among women using hormones and whether diagnosis
may be influenced by hormone effects on mammography.
Objective To determine the relationship among estrogen plus progestin use, breast
cancer characteristics, and mammography recommendations.
Design, Setting, and Participants Following a comprehensive breast cancer risk assessment, 16 608
postmenopausal women aged 50 to 79 years with an intact uterus were randomly
assigned to receive combined conjugated equine estrogens (0.625 mg/d) plus
medroxyprogesterone acetate (2.5 mg/d) or placebo from 1993 to 1998 at 40
clinical centers. Screening mammography and clinical breast examinations were
performed at baseline and yearly thereafter.
Main Outcome Measures Breast cancer number and characteristics, and frequency of abnormal
mammograms by estrogen plus progestin exposure.
Results In intent-to-treat analyses, estrogen plus progestin increased total
(245 vs 185 cases; hazard ratio [HR], 1.24; weighted P<.001)
and invasive (199 vs 150 cases; HR, 1.24; weighted P =
.003) breast cancers compared with placebo. The invasive breast cancers diagnosed
in the estrogen plus progestin group were similar in histology and grade but
were larger (mean [SD], 1.7 cm [1.1] vs 1.5 cm [0.9], respectively; P = .04) and were at more advanced stage (regional/metastatic
25.4% vs 16.0%, respectively; P = .04) compared with
those diagnosed in the placebo group. After 1 year, the percentage of women
with abnormal mammograms was substantially greater in the estrogen plus progestin
group (716 [9.4%] of 7656) compared with placebo group (398 [5.4%] of 7310; P<.001), a pattern which continued for the study duration.
Conclusions Relatively short-term combined estrogen plus progestin use increases
incident breast cancers, which are diagnosed at a more advanced stage compared
with placebo use, and also substantially increases the percentage of women
with abnormal mammograms. These results suggest estrogen plus progestin may
stimulate breast cancer growth and hinder breast cancer diagnosis.