The combination of increased parity and shorter breastfeeding duration might increase the odds of the least differentiated triple-negative breast cancer (BC) phenotype, theoretically because an expanded progenitor cell population from each pregnancy would incompletely differentiate postpartum. Subjects consisted of a consecutive case series of 2473 women treated for invasive breast cancer between 2001 and 2006. Breast cancer phenotype (triple-negative BC, vs non-triple-negative BC) was compared with reproductive and demographic information. Odds ratios (OR) with 95% confidence intervals (CIs) for the association of breastfeeding duration (months per child) and parity with triple-negative BC were calculated after adjusting for ethnicity, age at menarche, family history, and age at diagnosis. Compared with non-triple-negative BC, triple-negative BC was associated with shorter duration of breastfeeding per child (OR, 0.93; 95% CI, 0.90-0.97) and with higher parity (OR, 1.12; 95% CI, 1.06-1.20). By using multivariate logistic regression, triple-negative BC was independently associated with higher parity (OR, 2.76 [95% CI, 1.86-4.08] if ≥3 live births; OR, 1.89 [95% CI, 1.30-2.74] if ≤2 live births vs nulliparae), breastfeeding duration (OR, 0.55 [95% CI, 0.41-0.74] if >2 mo/child and OR, 0.58 [95% CI, 0.42-0.82] if ≤2 mo/child vs none), African American ethnicity (OR, 2.10; 95% CI, 1.52-2.92), and younger age at diagnosis (OR, 3.02 [95% CI, 2.03-4.47] if ≤40 years vs >60 years). Among women with invasive breast cancer, higher parity and the absence or short duration of breastfeeding were independently associated with triple-negative BC. Any duration of breastfeeding was found to be associated with lower probability of triple-negative BC, and the odds of this phenotype decreased with increasing duration of breastfeeding. Copyright © 2010 American Cancer Society.