Diet impacts triple-negative breast cancer growth, metastatic potential, chemotherapy responsiveness, and doxorubicin-mediated cardiac dysfunction.

ABSTRACT

Anthracyclines are standard-of-care chemotherapy for the treatment of triple-negative breast cancer (TNBC). However, high anthracyclines cumulative doses increase heart failure risk. Designing therapeutic strategies that ameliorate cardiac toxicities without compromising oncologic efficacy are important to improve TNBC outcomes and survivorship. The purpose of this study was to determine the impact of diet on TNBC chemotherapeutic responsiveness and development of chemotherapy-induced cardiac damage. Female BALB/c mice fed a control, Western, Mediterranean, or Western + fish oil diet were injected with 1 × 106 4T1-luciferase TNBC into the mammary fat pad. Tumors grew for 21 days before surgical tumor resection, then mice were treated with 3.3 mg/kg i.v. doxorubicin for 3 weeks. Vevo (R) cardiac ultrasound was performed. Female nu/nu mice were placed on diets before 1 × 105  MDA-MB-231-luciferase TNBC were injected via the tail vein to induce the development of lung metastases. Mice were treated with saline or 3.3 mg/kg i.v. doxorubicin for 3 weeks, and the development of metastases visualized by IVIS (R). Consumption of a high-fat diet increased TNBC growth regardless of dietary pattern. Western diet-fed mice developed lung metastases sooner and displayed increased lung metastatic lesion formation, which was not observed in Mediterranean diet-fed mice. Western diet-fed animals displayed worse cardiac function when compared with Mediterranean diet-fed animals. Hearts from Western diet-fed animals displayed increased fibrosis. Diet represents a modifiable component directly impacting tumor growth, antitumor chemotherapy efficacy, and cardiac toxicities. Our data suggest that the Mediterranean diet may reduce lung metastatic lesions formation and prevent the development of cardiac toxicities.