Jared W. Magnani

Chronic stress affects immune function and hormonal signaling and has been hypothesized to be associated with breast cancer, although results from the few prior studies are mixed and have not examined potential differences by estrogen receptor (ER) status. Using the Women's Health Initiative study, we included 76,951 postmenopausal women followed for events for a median of 16.7 years to investigate the association between baseline self-reported stressful life events and incident breast cancer by ER status and whether the association was modified by social support. We generated Cox proportional hazards models adjusting for demographic, clinical, lifestyle/behavioral, and social factors to estimate HRs and 95% confidence intervals (95%CI). The mean age was 63 (SD, 7.3), and majority of participants were White race (83.5%) and married or in a marriage-like relationship (63.0%). In analyses stratified by ER status, there was no relationship between stressful life events and ER-positive breast cancer. In contrast, compared with women in the lowest quartile, those in higher quartiles had an increased risk of ER-negative breast cancer, where those in quartile 4 had the highest risk (Quartile 4 vs. Quartile 1; HR = 1.30; 95%CI, 1.01–1.68; Ptrend = 0.050). Moreover, associations were stronger for the highest versus lowest quartile of stressful life events among widowed women (HR = 2.39; 95%CI, 1.29–4.44; Pinteraction<0.001). Association between stressful life events and ER-negative breast cancer was not modified by social support. In this cohort of postmenopausal women, higher experiences of prediagnostic stressful life events were associated with increased risk of ER-negative breast cancer. Prevention Relevance: Epidemiologic studies on the association between psychosocial stress and breast cancer risk remain inconsistent, while investigation of whether the association differs by ER status is limited. In this prospective cohort of postmenopausal women, high experiences of stressful life events were positively associated with ER-negative disease but not ER-positive.