Obesity Associated Factors Are Inversely Associated With Circulating Tumor Cells In Metastatic Breast Cancer

Background: Elevated levels of circulating tumor cells (CTCs) are associated with adverse outcomes in metastatic breast cancer (BC). However, relationships between CTCs and various patient-related factors that may impact outcome remain undefined. Consequently, associations of CTC counts with obesity and metabolic factors were evaluated in order to gain insight into potential interactions between patient physiology and disease burden. We hypothesized that obesity and associated metabolic factors would be associated with higher CTC counts. Methods: Non-diabetic women with metastatic BC beginning a new line of treatment due to progressive disease were recruited from four Ontario cancer hospitals between February 2013 and April 2015. Patients provided blood for CTC analysis, which was completed within 72 hours of collection using the Janssen CellSearch platform. Fasting serum was also collected for assessment of metabolic factors including glucose (mmol/L), insulin (pmol/L), leptin (ng/mL) and adiponectin (ng/mL). Associations of CTC counts with these factors, as well as anthropometric measurements (height (cm), weight (kg), BMI (kg/m2)) were evaluated using Pearson correlation coefficients after transforming the variables involved to normality. For CTC counts, the log transformation with half integer correction was used. Results: 96 patients with a median age of 60.5 years completed the study. Most were post-menopausal (87, 90.6%) and exhibited grade II/III tumors (75, 78.1%). The majority of patients had hormone receptor positive disease (83, 86.5%), but 16.7% (16) were HER2 positive and 10.4% (10) were triple negative. The number of CTCs observed ranged from 0 to 1238 (median 2, geometric mean 3.63). No CTCs were detected in 29 patients (30.2%), whereas 25 patients (26 %) exhibited counts of 1 to 4 CTCs and 42 (43.8%) had 5 or more CTCs. CTCs were not significantly associated with tumor characteristics including ER/PgR, HER2, grade, stage (T/N) or lymphovascular invasion. The number of CTCs inversely correlated with BMI (r=-0.26, p=0.01), leptin (r=-0.29, p=0.004), and leptin-adiponectin ratio (r=-0.3, p=0.004). A similar trend that approached significance was noted for body weight (r=-0.19, p=0.07), insulin (r=-0.19, p=0.06) and homeostatic model assessment (HOMA, an estimate of insulin resistance, r=-0.2, p=0.055). Conversely, adiponectin (r=0.18, p=0.07) and height (r=0.18, p=0.07) were positively associated with CTC counts in correlations that neared significance. No associations were observed for age (r=0.09, p=0.4) or glucose (r=-0.09, p=0.4). Conclusions: Obesity associated metabolic factors including weight, BMI, insulin, HOMA and leptin were inversely associated (and adiponectin and height positively associated) with CTC counts. These patterns are consistent with weight loss and/or cachexia in women with elevated CTC counts who have higher disease burden. Additional analyses are underway to further characterize these associations and include assessment of serum albumin, free fatty acids, creatine kinase and hepcidin. Citation Format: Dowling RJO, Chang MC, Lohmann AE, Ennis M, Amir E, Elser C, Brezden-Masley C, Vandenberg T, Lee E, Fazaee K, Stambolic V, Goodwin PJ. Obesity associated factors are inversely associated with circulating tumor cells in metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-02-09.