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Purpose: Early-stage breast cancers are biologically heterogeneous and vary in clinical behavior, supporting the role of factors other than tumor size and lymph node involvement as outcome determinants. We evaluated the effect of epidemiologic breast cancer risk factors on recurrence in women with early-stage disease., Patients and Methods: Medical records from 2,327 women with early-stage breast cancer, treated at the M.D. Anderson Cancer Center between 1985 and 2000, were used to derive information on epidemiologic, clinical, and histological factors. Cox proportional hazards models were used to estimate the hazard ratios of 5-year risk of breast cancer recurrence adjusted for treatment and stage. Statistical tests were two-sided., Results: None of the breast cancer risk factors were associated with recurrence, adjusting for tumor characteristics and treatment. A significant interaction between hormone replacement therapy (HRT) use and tumor hormone receptor status on risk of recurrence (P = .0003) was observed. Among ever-users of HRT, recurrence risk was two-fold lower for estrogen receptor (ER)--positive and progesterone receptor (PR)--positive tumors compared with ER- and PR-negative tumors; whereas, among never-users of HRT, there was no statistically significant association between recurrence risk and receptor status., Conclusion: HRT users who develop receptor-positive early-stage disease have better outcomes than those who develop receptor-negative disease. Among never-users of HRT, the expected beneficial effect of ER- or PR-positive tumors on recurrence risk was absent. These data lend support to the notion that the biology of hormone receptor-positive disease in HRT users differs from that in nonusers.