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Introduction: Lifestyle factors and metabolic derangements have wide-ranging effects including on immune activity. The association of circulating immune cells and outcomes in patients with early stage breast cancer remain incompletely understood. Objective: To evaluate the effects of smoking, body mass index (BMI), and alcohol intake on the association between circulating immune cell levels and patient outcomes. Methods: We retrospectively screened the electronic medical record of 950 patients with early stage breast cancer at the Johns Hopkins Hospital between 2003-2008 with at least 5 years of follow-up data for information on complete blood cell (CBC) counts. Absolute lymphocyte, monocyte, and neutrophil counts were obtained from the CBC differential performed closest to time of diagnosis within a period of ±1 year, and prior to any systemic treatment. Statistical analyses used were t-test for comparison of recurrence vs non-recurrence and Cox proportional hazard models for survival analysis, and linear regression for association between counts and BMI. Covariates adjusted for include grade, stage, smoking status, and alcohol use. Results: A total of 433 patients with stage 0-III breast cancer had complete data and were included in the analytical population. The populations of analyzed and non-analyzed patients were not significantly different in age or ethnic composition. The median age was 53 years old (range 26-86); 24% (n=103) were African American, and 76% (n=330) were Caucasian. Median BMI at baseline was 27 (range 18-53). Breast cancer subtypes were 68% (n=293) hormone receptor-positive, 19% (n=82) HER2 positive, and 13% (n=53) triple negative. 7.6% (n=33) experienced a recurrence and 6.9% (n=30) died of all causes. Patients with the highest quartile of lymphocytes at diagnosis, compared to the lowest quartile, had a significantly lower risk of recurrence (HR=0.23, 95% CI [0.06, 0.87], p=0.031). Patients with the highest quartile of monocytes were also at a lower risk for recurrence (HR= 0.17, 95% CI [0.11, 0.72] p=0.02). This effect was magnified in subgroup analysis among patients with hormone negative (n=125, p=0.017) and grade 3 (n=155, p=0.02) breast cancer. Patients in the highest quartile of both lymphocytes and monocytes had similarly lower recurrence rates (HR=0.24, 95% CI [0.08, 0.88] p=0.034). In subgroup analysis with regard to lifestyle factors, association of higher monocytes with lower recurrence was most significant among those consuming alcohol (n=237, p=0.005). Subgroup analysis of alcohol use was unremarkable for lymphocytes, as was subgroup analysis of smoking history (n=144) for lymphocytes and monocytes. In patients with BMI>30, lower lymphocytes were more strongly associated with recurrence (n=144, p=0.04); conversely, in patients with BMI Conclusion: Higher recurrence rates are observed in patients with early stage breast cancer who have low-normal lymphocyte and monocyte counts at time of diagnosis. This association is stronger in subgroups of patient with high BMI and who consume alcohol, known risk factors for breast cancer. Citation Format: Eric G Xie, Maya M Lapinski, Sarah Talamantes, Kala Visvanathan, Antonio Wolff, Cesar Santa-Maria. Association of circulating immune cells with lifestyle factors, and recurrence and mortality in patients with early stage breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-04-16.