OBJECTIVE: To examine associations among life events stress, social support, and breast cancer incidence in a cohort of postmenopausal women. DESIGN AND MAIN OUTCOME MEASURE: Women's Health Initiative observational study participants, breast cancer free at entry, who provided assessment of stressful life events, social support, and breast cancer risk factors, were prospectively followed for breast cancer incidence (n = 84,334). RESULTS: During an average of 7.6 years of follow-up, 2,481 invasive breast cancers were diagnosed. In age-adjusted proportional hazards models, 1 stressful life event was associated with increased risk, but risk decreased with each additional stressful life event. After adjustment for confounders the decreasing risk was not significant. Stressful life events and social support appeared to interact in relation to breast cancer risk such that women who had greater number of stressful life events and low social support had a decreased risk of breast cancer. CONCLUSIONS: This study found no independent association between stressful life events and breast cancer risk. The results are compatible with a more complex model of psychosocial factors interacting in relation to breast cancer risk.