Postmenopausal Estrogen and Progestin Use in Relation to Breast Cancer Risk

Postmenopausal Estrogen and Progestin Use in Relation to Breast Cancer Risk1

University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin 53706 [P. A. N., A. T-D.]; Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 [P. A. N., B. E. S.]; Department of Community Medicine, Dartmouth Medical School, Hanover, New Hampshire 03756 [L. T-E., J. A. B.]; Departments of Epidemiology [K. M. E., W. C. W., M. J. S.] and Nutrition [W. C. W., M. J. S.], Harvard School of Public Health, Boston, Massachusetts 02115; and Channing Laboratory, Harvard Medical School and Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts 02115 [W. C. W., M. J. S.]

Abstract

Epidemiological evidence now consistently supports a modestincrease in breast cancer risk among women using postmenopausal hormones, usually estrogens.Less is known regarding how the addition of progestin affects breast cancer risk. The objective of this study was to investigate the type and duration of postmenopausal therapy and breast cancer risk. We performed a multicenter population-based case-control study set in Massachusetts, New Hampshire, and Wisconsin. The subjects were 5298 postmenopausal women (age range, 50–79 years) with a new diagnosis of invasive breast cancer from statewide tumor registries. For comparison, 5571 controls were randomly selected from population lists. Participants completed a structured telephone interview covering hormone use and breast cancer risk factors. Multivariable regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). The RR for breast cancer increased with longer durations of hormone use, about 2%/year for estrogen alone (RR, 1.02; 95% CI, 1.01–1.03) and 4%/year for estrogen-progestin use (RR, 1.04; 95% CI, 1.01–1.08). Estrogen-progestin use that was both recent and long term (>5 years in duration) was more strongly associated with breast cancer risk (RR, 1.57; 95% CI, 1.15–2.14) than similar use of estrogen alone (RR, 1.39; 95% CI, 1.17–1.65). In estrogen-progestin users, risks were similar for sequential and continuous use regimens but perhaps stronger for lobular than ductal breast cancer. Use of progestin alone was associated with a doubling of risk (RR, 2.09; 95% CI, 1.07–4.07 for ever use versus nonuse). Estrogen-progestin use, both sequential and continuous, appears to be more strongly associated with risk of breast cancer than use of estrogen alone.

Footnotes

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↵1 Supported by NIH Grants CA47147, CA69664, and CA47305.
↵2 To whom requests for reprints should be addressed, at University of Wisconsin Comprehensive Cancer Center, Room 307, WARF Building, 610 Walnut Street, Madison, WI 53726.
↵3 The abbreviations used are: CI, confidence interval; RR, relative risk; OR, odds ratio; SE, standard error.
- Accepted April 3, 1902.
- Received August 17, 1901.
- Revision received March 22, 1902.