The role of hormone replacement therapy in the risk for breast cancer and total mortality in women with a family history of breast cancer

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 big her 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.