Abstract

Background: Disseminated tumor cells (DTCs) are found in approximately one third of clinical stage I-III breast cancer (BC) patients, and published reports show that presence of DTCs is an independent predictor of outcome. While higher body mass index (BMI) is associated with increased risk of breast cancer recurrence and lower survival rates in BC patients, women with lower BMIs may have lower bone density and higher bone turnover. We hypothesized that increases in bone turnover may result in the release of bone growth and “homing” factors that facilitate BC metastasis to bone and provide a “pre-metastatic niche” for BC cells. The purpose of this study was to determine if a correlation existed between DTCs and BMI in early stage BC patients. Methods: We obtained informed consent and collected bone marrow samples from 262 clinical stage I-III BC patients who were participants in an IRB-approved clinical study from 2/2005- 2/2010. All marrow samples were collected at the time of surgery for the primary tumor. DTCs were assessed using anti-pancytokeratin (CK) antibody cocktail (AE1/AE3, CAM5.2, MNF116, CK8 and 18) following cytospin. The presence of one or more CK positive cells meeting morphologic criteria for malignancy was considered a positive result for DTC. Patients with a BMI of (18.5 — 24.9) kg/m 2 were considered “normal weight”, those with a BMI of (25 - 29.9) kg/m 2 “overweight” and a BMI greater than 30 kg/m 2 was used to designate them as “obese”. Information on clinicopathological factors including BMI (measured on initial presentation) was obtained from a prospective database. Statistical analyses used Chi-square and non-parametric tests for trend. Results: Median follow-up was 19 months and mean age was 53 (25-80) years. Eighty-four patients (32%) were normal weight, 85 (32%) were overweight and 91 (35%) were obese. Seventy-eight (30%) patients had DTCs present at the time of assessment. Obese patients were significantly less likely to show presence of DTCs as compared to those who had a BMI 2 (20/78; 26% vs. 71/184; 39%) {O.R. = 0.55, 95% C.I. = 0.29- 0.96, P = 0.03}. DTCs were also less likely to be found in patients with BMI ≥25 kg/m 2 as compared to those with BMI 2 (40/78; 51% vs. 136/184; 74%); {O.R. = 0.42, 95% C.I. = 0.04- 1.02, P = 0.03}. No statistically significant correlation was observed between primary tumor characteristics (ER, PR, HER2, lymph node status, tumor grade) and presence of DTCs. Finally, a non-parametric analysis demonstrated a trend in occurrence of DTCs across the ordered levels of patients’ BMI values (P= 0.013). Conclusions: DTCs were much more common in patients with lower BMI. Further studies are needed to determine if patients with low BMI have unique microenvironmental factors within the bone that predisposes them to tumor cell dissemination. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-02-02.

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