Hormone Replacement Therapy, Family History, and Breast Cancer Risk Among Postmenopausal Women

Background: Evidence is mixed regarding how familial predisposition to breast cancer affects the relation between hormone replacement therapy and risk of postmenopausal breast cancer. We investigated whether the risk difference for invasive breast cancer attributable to estrogen plus progesterone replacement therapy is greater among women with a first-degree family history of the disease. Methods: This study is a longitudinal follow-up of 16,608 postmenopausal women aged 50-79 years who were enrolled between 1993 and 2002 in the Women's Health Initiative randomized trial of estrogen plus progesterone replacement therapy versus placebo. Results: Three hundred forty-nine cases of invasive breast cancer occurred during a mean follow-up period of 5.6 years. The invasive breast cancer risk difference attributable to the hormone therapy was 0.007 among women with first-degree family history and 0.005 among the others, resulting in a negligible interaction contrast (IC = 0.002; 95% confidence interval = -0.014 to 0.018). The interaction contrast restricted to estrogen-receptor-positive invasive breast cancers was also negligible (IC = -0.006; 95% CI = -0.021 to 0.008). Conclusion: Family history and estrogen plus progesterone replacement therapy have independent and noninteracting effects on the risk of invasive breast cancer among participants in the Women's Health Initiative randomized trial.