10518 Background: Although current use of hormone replacement therapy (HRT) is associated with a greater risk of breast cancer than past use, the effects of longer term past use of HRT are not well quantified. Methods: We examined the relationship between past HRT use and invasive breast cancer risk within the Nurses’ Health Study, a prospective cohort of 121,700 registered nurses aged 30–55 in 1976 who update information on cancer risk factors and outcomes through biennial questionnaires. For this analysis, the follow-up period was 1980 through 2004 and only included person-time for postmenopausal women. Status of HRT use (never, past, or current), type of HRT (oral unopposed estrogen (E alone) or combination oral estrogen + progesterone (E+P)), and duration of HRT use were assessed every 2 years and defined prospectively. Proportional hazards models controlled for age, body mass index, parity, age at first birth, family history of breast cancer, benign breast disease, alcohol consumption, type of menopause, and ages at menarche and menopause. Results: During 1,388,368 person-years of follow-up among postmenopausal women, invasive breast cancer was diagnosed among 1,554 women who had never used HRT, 459 past users of E+P and 527 past users of E alone. Regardless of duration of use, past use of E alone was not associated with breast cancer risk. Although past use of E+P for less than 10 years was not associated with breast cancer risk (RR (95% CI) 1.01 (0.88–1.17) for < 5 years and 0.95 (0.74–1.21) for 5–9.9 years), past use of E+P for greater than 10 years was associated with an increased risk of breast cancer (RR 1.53 (1.09–2.16) for 10–14.9 years and 1.48 (0.87–2.51) for 15 or more years). Results were similar regardless of time since last use, although power was limited for this subgroup analysis. Conclusions: Past use of E+P for greater than 10 years was associated with a persistent elevation in breast cancer risk. The relationship between duration of past use and breast cancer risk did not appear linear, but suggested a possible threshold effect. No significant financial relationships to disclose.
Lack of Effect Modification between Estrogen Metabolism Genotypes and Combined Hormone Replacement Therapy in Postmenopausal Breast Cancer Risk: Table 1.
