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Chen C, Weiss NS, Newcomb P, Barlow W, White E. Hormone Replacement Therapy in Relation to Breast Cancer. JAMA. 2002;287(6):734–741. doi:10.1001/jama.287.6.734
Author Affiliations: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, and Department of Epidemiology (Drs Chen, Weiss, Newcomb, and White), and Center for Health Studies, Group Health Cooperative, and Department of Biostatistics (Dr Barlow), University of Washington, Seattle.
Context Studies of long-term hormone replacement therapy (HRT) suggest an associated
increased risk of breast cancer, but whether this association differs according
to histologic type of cancer has not been extensively studied.
Objective To determine whether the association between HRT and risk of breast
cancer varies by HRT formulation and differs across histologic cancer types.
Design, Setting, and Participants Nested case-control study among 705 postmenopausal women enrolled in
the Group Health Cooperative of Puget Sound (GHC) who were aged 50 to 74 years
and had primary invasive breast cancer diagnosed between July 1, 1990, and
December 31, 1995 (cases), and 692 randomly selected aged-matched female members
of GHC (controls).
Main Outcome Measure Incidence and type of breast cancer by duration of HRT use in the 5-year
period ending 1 year before diagnosis, which was ascertained from computerized
Results The incidence of breast cancer, all histologic types combined, was increased
by 60% to 85% in recent long-term users of HRT, whether estrogen alone or
estrogen plus progestin. Longer use of HRT (odds ratio [OR], 3.07 for 57 months
or more; 95% confidence interval [CI], 1.55-6.06) and current use of combination
therapy (OR, 3.91; 95% CI, 2.05-7.44) were associated with increased risk
of lobular breast cancer. Long-term HRT use was associated with a 50% increase
in nonlobular cancer (OR, 1.52 for 57 months or more; 95% CI, 1.01-2.29).
Conclusion Our data add to the growing body of evidence that recent long-term use
of HRT is associated with an increased risk of breast cancer and that such
use may be related particularly to lobular tumors.
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