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The Role of Hormone Replacement Therapy in the Risk for Breast Cancer and Total Mortality in Women with a Family History of Breast Cancer

Thomas A. Sellers, PhD; Pamela J. Mink, MS; James R. Cerhan, MD, PhD; Wei Zheng, MD, PhD; Kristin E. Anderson, PhD; Lawrence H. Kushi, ScD; and Aaron R. Folsom, MD
[+] Article and Author Information

From the University of Minnesota, Minneapolis, Minnesota; and the University of Iowa, Iowa City, Iowa. Disclaimer: The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Grant Support: By grant R01 CA39742 from the U.S. National Cancer Institute. Ms. Mink was supported by a training grant (T32CA09607) from the National Cancer Institute to Dr. Les Robison. Requests for Reprints: Thomas A. Sellers, PhD, Division of Epidemiology, University of Minnesota, 1300 South Second Street, Suite 300, Minneapolis, MN 55454. Current Author Addresses: Drs. Sellers, Zheng, Anderson, Kushi, and Folsom and Ms. Mink: Division of Epidemiology, University of Minnesota, 1300 South Second Street, Suite 300, Minneapolis, MN 55454.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1997;127(11):973-980. doi:10.7326/0003-4819-127-11-199712010-00004
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Background: The risks and benefits of hormone replacement therapy (HRT) are of considerable interest and importance, especially in terms of whether they differ among subsets of women.

Objective: To determine whether HRT is associated with increased risks for breast cancer and total mortality in women with a family history of breast cancer.

Design: Prospective cohort study.

Setting: Population-based sample of midwestern postmenopausal women enrolled in an observational study of risk factors for cancer.

Participants: Random sample of 41 837 female Iowa residents 55 to 69 years of age.

Measurements: Incidence rates of and relative risks for breast cancer (n = 1085) and total mortality (n = 2035) through 8 years of follow-up were calculated by using data from the State Health Registry of Iowa and the National Death Index.

Results: A family history of breast cancer was reported by 12.2% of the cohort at risk. Among women with a family history of breast cancer, those who currently used HRT and had done so for at least 5 years developed breast cancer at an age-adjusted annual rate of 61 cases per 10 000 person-years (95% CI, 28 to 94 cases); this rate was not statistically significantly higher than the rate in women who had never used HRT (46 cases per 10 000 person-years [CI, 36 to 55 cases]). Among women with a family history, those who used HRT had a significantly lower risk for total mortality than did women who had never used HRT (relative risk, 0.67 [CI, 0.51 to 0.89]), including total cancer-related mortality (relative risk, 0.75 [CI, 0.50 to 1.12]). The age-adjusted annual mortality rate for women using HRT for at least 5 years was 46 deaths per 10 000 person-years (CI, 19 to 74 deaths); this is roughly half the rate seen in women who had never used HRT (80 deaths per 10 000 person-years [CI, 69 to 92 deaths]).

Conclusions: These data suggest that HRT use in women with a family history of breast cancer is not associated with a significantly increased incidence of breast cancer but is associated with a significantly reduced total mortality rate.

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