Abstract Women of African ancestry are more likely than women of European ancestry to be diagnosed with aggressive tumors characterized by negative staining for estrogen receptors (ER) and progesterone receptors (PR). Reasons for the disparity are unclear, and previous studies have lacked statistical power to investigate risk factors for the more aggressive subtypes. A recent report from the Carolina Breast Cancer Study indicated that basal-like breast cancer, a subtype of breast tumors with ER-, PR-, HER2-, HER1+ and/or CK5/6+ characteristics, was positively associated with increased parity, whereas other subtypes were inversely associated with parity. The increased risk of basal-like cancer was strongest for parous women who had never breastfed. The majority of breast tumors with negative staining for both ER and PR would likely be classified as basal-like. We examined the relation of parity and lactation to risk of ER-/PR- breast cancer among 59,000 African American women from the Black Women's Health Study in 12 years of follow-up data. Reproductive history was obtained by questionnaire at baseline in 1995 and updated every two years. ER and PR status were obtained from pathology reports and state cancer registry records. Included in this analysis were 809 incident breast cancer cases with complete data on ER and PR status, with 285 classified as ER-/PR-, 395 as ER+/PR+, 114 as ER+/PR-, and 15 as ER-/PR+. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were derived from proportional hazard models for the relation of each reproductive factor to risk of specific tumor subtype, with control for all other reproductive factors, age, region, education, body mass index, waist-hip ratio, hormone use, alcohol, smoking, and physical activity. Risk of ER-/PR- breast cancer increased with increasing parity (p trend = 0.02), whereas risk of ER+/PR+ cancer decreased with increasing parity (p trend = 0.0002). For ER-/PR- breast cancer, the IRR for women who had 3+ births and never breastfed relative to nulliparous women was 1.66 (95% CI 1.09-2.54). The increased risk associated with higher parity was ameliorated by breast feeding: the comparable IRR for women who had 3+ births but breastfed at least one of the babies was 1.01 (95% CI 0.63-1.63). These results from a cohort of African American women support findings from the previous study of basal-like breast cancer and are consistent with the hypothesis that pregnancy and breastfeeding may influence risk of ER-/PR- cancer through inflammatory/immune system alterations linked to mammary gland involution. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5737.