Plastic Surgery Research Council
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PSRC 60th Annual Meeting

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The Role of Obesity and Breast Adipose Tissue in Breast Cancer Formation
Naveen Kumar, MD, Irene Pien, BA, Michele Bowie, BA, Catherine Ibarra-Drendall, PhD, Matthew Sweede, BA, Victoria Seewaldt, MD, Scott T. Hollenbeck, MD.
Duke University Medical Center, Durham, NC, USA.

The Role of Obesity and Breast Adipose Tissue in Breast Cancer Formation
Naveen Kumar, Irene Pien, Michele Bowie, Catherine Ibarra-Drendall, Matthew Sweede, Victoria Seewaldt, Scott T. Hollenbeck
Purpose: Obesity is a major risk factor for breast cancer and an adverse prognostic indicator. We hypothesize that adipose tissue may release numerous cytokines that are associated with breast cancer progression. To test this hypothesis, we evaluated the obesity related cytokines; Leptin (Lp), Adiponectin (Adp) and Monocyte Chemoattractant Protein 1 (MCP-1) at the serum, tissue and cellular level.
Methods: IRB Approved Clinical Study: Peripheral blood was taken from 74 women followed in our high risk breast cancer clinic. Serum was evaluated using ELISA to quantify Adp, Lp and MCP-1 levels and this was correlated with BMI. In 4 patients with a unilateral breast cancer, Lp and MCP-1 levels were measured from left and right breast adipose tissue effluent following bilateral mastectomies. In Vitro: Adipose derived stem cell (ASC’s), mature adipocyte (MA) and dermal fibroblast (DF) conditioned media was evaluated for production of Lp, Adp and MCP-1 using ELISA or membrane antibody array.
Results: (1) Serum: In high risk patients, serum Lp levels were 11899 +/- 9668 pg/ml in normal weight individuals (N=25), 22117 +/- 15235 pg/ml in overweight individuals (N=28) and 27800 +/- 10628 pg/ml in obese individuals (N=21) (p<0.05, ANOVA). In the same patient cohort, Adp levels were 14096269 +/- 9537649 pg/ml in normal weight individuals, 13295715 +/- 11307016 pg/ml in overweight individuals and 13740182 +/- 16182231 pg/ml in obese individuals (NS). Finally, serum MCP-1 levels were 142 +/- 107 pg/ml in normal weight individuals, 159 +/- 108 pg/ml in overweight individuals and 172 +/- 166 pg/ml in obese individuals (p=0.7; ANOVA). (2) Tissue: Breast adipose tissue cytokines were measured from 4 bilateral mastectomy patients. Three patients had unilateral invasive carcinoma and one patient had unilateral DCIS. Mean age was 41 years (range 35-44). The mean BMI was 29.3 (range 20.8 - 34.4). In breast adipose tissue effluent from bilateral mastectomies, mean MCP-1 levels were higher in the invasive cancer side (6364 +/- 217 pg/ml versus 5606 +/- 442 pg/ml; p=0.03, paired T-test) (Figure 1A). Lp levels did not correlate with cancer laterality. (3) Cellular: MA’s produced significantly more soluble Adp and Lp than ASCs and DFs (p<0.05). In 5 primary ASC lines derived from the adipose tissue of mastectomy specimens; MCP-1 was prominently expressed (Figure 1B).
Conclusion: Serum adipokines are related to BMI in patients at high risk for breast cancer. Within the adipose tissue of matched bilateral mastectomy specimens, MCP-1 levels are elevated in the breast that contains the invasive cancer. Leptin and Adiponectin are released by mature adipocytes while MCP-1 is released from ASC’s. The role of adipose tissue in breast cancer formation may be related to the preponderance of cytokines released by both mature adipocytes and ASC’s from systemic and local environments.


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