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Chi-Ling Chen, PhD; Noel S. Weiss, MD,DrPH; Polly Newcomb, PhD; William Barlow, PhD; Emily White, PhD

JAMA. 2002;287:734-741.

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 pharmacy records.

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.

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.

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