Background: Obesity and other factors contributing to metabolic syndrome (MS) have become increasingly prolific in today's population. They are also known risk factors or comorbidities in many disease states including breast cancer (BC). While obesity and MS are known to increase the risk of developing BC, the effect on the risk of distant recurrence is uncertain. This substudy evaluated the relationship of BMI, blood pressure, cholesterol, triglyceride, diabetic status, and MS on the risk of recurrence in early BC patients. Methods: The effect of these metabolic factors on MammaPrint (MP) and Oncotype DX (ODX) risk of recurrence assays was compared. Additionally, gene expression analysis was performed to elucidate the differences between obese patients who were MP high risk (HR) vs. low risk (LR), and MP HR patients who were obese vs. not-obese. This subanalysis included patients from the PROMIS (n=198) and IMPACt (n=382) studies for whom metabolic characteristics were captured with informed consent. From the IMPACt study, 98 patients also reported ODX results (RS range 0-69). Results: By BMI, 1% of patients were classified as underweight (BMI <18.5), 22% normal (18.5≤ BMI <25), 31% overweight (25≤ BMI <30), and 46% as obese (BMI ≥30). To be classified as having MS, the patient had to exhibit any 3 of the 5 metabolic factors. In the full cohort, having MS was significantly associated with ethnicity (p < 0.05) and menopausal status (p < 0.001), but not histopathological tumor type, histological grade, tumor stage, or lymph node status (p > 0.05). 36% (207/580) of patients were considered as having MS in the full cohort, similarly 36% (35/98) had MS in the ODX subset. Of the patients with MS, MP classified 52% (108/207) as HR. For the subset of ER-positive patients with an ODX result, ODX classified the 11% (4/35) as HR whereas MP classified 57% (20/35) of the same patients as HR. Conclusions: Patients with obesity as measured by BMI and with MS were more frequently classified as HR by MP, in contrast to ODX which classified nearly all patients as intermediate or LR, confirming previous findings by Robinson, et. al (SABCS 2012 and 2014). Understanding the biological foundation of how obesity and metabolic factors affect risk of recurrence in breast cancer will improve both the treatment and care of patients.

Citation Format: Soliman H, Treece T, Audeh W, IMPACt Investigators Group I. The effect of obesity and metabolic factors on genomic assays for risk of recurrence [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-02-05.