Abstract 5189: Caloric restriction augments the chemotherapeutic response in a murine triple negative breast cancer model

Abstract

Abstract Purpose: Triple negative breast cancers (TNBC) are a highly aggressive subtype of breast cancer, linked with a poor prognosis. TNBC tumors have a higher propensity for metastasis and unfortunately have fewer treatment options due to their lack of estrogen, progesterone or Her-2/neu receptors. We sought to determine if caloric restriction (CR) could augment the response of chemotherapy including docetaxel and cisplatin in a TNBC model and improve survival. Methods: An orthotopic mouse model using a highly metastatic, luciferase-tagged TNBC cell line (4T1), was used to generate palpable tumors. Mice were then treated with CR, cisplatin alone, docetaxel alone or a combination of CR and chemotherapy. Three times a week, primary tumors were measured with calipers and in vivo imaging was performed to evaluate the metastatic burden of disease. Molecular evaluation of the tumors was performed, generating a mechanistic hypothesis for increased sensitivity to chemotherapy. Results: Combining either docetaxel or cisplatin with CR, significantly decreased the rate of primary tumor growth (p<0.001). Average time to metastases (19 days in ad lib group) was increased by an average of 10.5 +/- 3 days with the addition of either docetaxel or cisplatin, and increased by an additional 6 days in the CR+cisplatin (35 days until metastases, p<0.01). The addition of CR to chemotherapy decreased the overall number and volume of lung metastases, and increased overall survival as compared with those groups receiving chemotherapy alone. Molecularly, CR was noted to augment the effect of chemotherapy by decreasing inflammation that results from IL-1β mediated acute RT toxicity and molecular effectors in the insulin (insulin, IGF-1, IGF-BP3 and IGF-1R) and adipokine signaling pathways (decreased leptin and increased adiponectin). Conclusions: CR augments the effect of systemic chemotherapy in an aggressive TNBC mouse model, in part by decreasing the inflammatory response. The novel use of CR in combination with systemic chemotherapy has the potential to enhance clinical outcomes for patients with triple negative breast cancer and should be tested in the clinical setting. Citation Format: Brittany Simone, Tu Dan, Ajay Palagani, Meredith LaRose, Jason E. Savage, Nicole Simone. Caloric restriction augments the chemotherapeutic response in a murine triple negative breast cancer model. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5189.