Abstract Introduction: Obesity is associated with a more aggressive breast cancer and a worse outcome following chemotherapy treatment. Triple negative breast cancer is a highly aggressive subtype of breast cancer characterized by the absence of estrogen, progesterone, and human epidermal growth factor-2 (HER2) receptors. This subtype has also been correlated with a worse prognosis. This study aims to investigate the impact of obesity on triple negative breast cancer cells’ response to chemotherapy treatment and elucidate potential therapeutic options to improve response. Methods: Sera was collected from breast cancer patients at the Cancer Therapy and Research Center at The University of Texas Health Science Center at San Antonio (UTHSCSA) and pooled according to body mass index (BMI) category (Control:18.5 to 24.9 kg/m2; Obese:≥30 kg/m2). MDA-MB-231 cells, a triple negative breast cancer cell line, were grown in serum-free media supplemented with 2% obese or control patient sera to create an in vitro model of obesity. The effects of docetaxel, a chemotherapeutic agent, on cell viability in the presence of obese versus control sera were examined by MTT. Modulation of B-cell lymphoma 2 (Bcl-2), cyclooxygenase-2 (COX-2), and mammalian target of rapamycin (mTOR) were evaluated as possible mechanisms for obesity-induced chemotherapy resistance. Results: The obese sera significantly reduced sensitivity of the MDA-MB-231 cells to docetaxel. In fact, there was no variance in the viability level of cells grown in obese patient sera for 96 hours with and without docetaxel treatment. The mechanism for resistance does not appear to involve Bcl-2 or COX-2, previously implicated in docetaxel resistance. Intriguingly, suppression of mTOR did provide significant benefit, in agreement with our previous in vivo studies investigating obesity and aromatase inhibitor (AI) response. The role of the mTOR pathway in modulating therapeutic response is still being investigated. Conclusion: Exposure to obesity-associated circulating factors confers chemotherapy resistance in triple negative breast cancer cells. Further research will be conducted to determine the mechanism by which obesity promotes chemotherapy resistance and whether modulation of the mTOR pathway will provide significant benefit. Citation Format: Victoria R Lehrmann, Laura W Bowers, Andrew J Brenner, Linda A deGraffenried. Obesity confers chemotherapy resistance in triple negative breast cancer cells [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-05-13.
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