Abstract Initial observations in animal models suggest that heat seeking behavior occurs in animals with tumors, and that modest increases in ambient temperature can significantly delay and/or reduce tumor growth; this effect appears to be mediated by the immune system. As a first step in understanding the potential significance of thermal dysregulation in breast cancer survivors, the aim of this study was to determine if changes in body temperature and/or feelings of thermal discomfort are evident in breast cancer patients. We examined body temperature in 233 women participating in a prospective study of early-stage (I to IIIa) breast cancer patients from 2006 to 2009. Body temperature at the time of diagnosis and 12 months post-diagnosis was abstracted from medical records. Participants completed a comprehensive epidemiologic survey at enrollment and 12 months following diagnosis. A questionnaire was also designed to collect information on patients’ experience with thermal discomfort, focusing on feelings of being “inappropriately and excessively cold” and “hot flashes and sweats”. The questionnaire was completed by 159 participants one year after diagnosis. General linear models and unconditional logistic regression was performed to examine associations between body temperature and symptoms of thermal discomfort, and epidemiologic and clinical risk factors. All analyses were adjusted for race and season of cancer diagnosis. Prior to cancer treatment, body temperature at diagnosis appeared to be higher among women with higher nuclear grade cancers (II and III vs I, P=0.05) and those with ≥ 3 positive nodes compared to those with ≤ 2 (p=0.04). Body temperature, however, did not change from time of cancer diagnosis to 12 months following diagnosis (p=0.12). When change in body temperature was examined with respect to clinical and epidemiologic factors, declines in body temperature were found to be significantly associated with younger age at diagnosis (p=0.0005), premenopausal status at diagnosis (p=0.001), being nulliparous (p=0.01), treatment with chemotherapy (p=0.0002), and treatment with tamoxifen, but not anastrozole (p=0.004). Among the 159 participants who completed the thermal discomfort questionnaire at 12 months following diagnosis, 40% of patients reported that they felt cold at least occasionally in the past 7 days compared to 67% who reported having hot flashes. As expected, reports of hot flashes were associated with hormonal treatment (p=0.02), although family history of breast cancer also increased the likelihood of reporting hot flashes (OR=2.56, 95% CI 1.09, 6.01). In contrast, likelihood of feeling inappropriately cold was not associated with hormone therapy, but was associated with chemotherapy treatment (OR = 1.96, 95% CI: 1.00, 3.82). These results together suggest that changes in body temperature regulation may occur in breast cancer patients and that this may be evident prior to breast cancer treatment. 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 906.