A Cardio-Oncological Mice Model of Anthracycline-Induced Cardiotoxicity in Breast Tumor-Bearing Immunocompetent Mice.

The recent update from the European Society of Cardiology on preclinical models of cancer therapy-related cardiac dysfunction highlights a critical need for more representative and translational in vivo models. It pinpoints the need to develop models that employ immunocompetent, tumor-bearing animals, incorporating multiple strains and both sexes, to more accurately recapitulate the heterogeneity observed in clinical populations. Therefore, a clinically relevant model of anthracycline-induced cardiotoxicity (AIC) in breast tumor-bearing animals was built. According to mice' genetic background, either 4T1Luc-cells (200k cells) or PY8119-cells (200k cells) were injected in Balb/c-mice or C57Bl/6J-mice, respectively subcutaneously in the lower mammary gland of males and females. Tumor growth was controlled with bioluminescence and palpation. Once the tumor mass was detectable by palpation, 2 weeks post-tumor cell injection, animals received anticancer Doxorubicin treatment. Mice's tolerance to Doxorubicin was strain-dependent. Cardiac function was evaluated before the start of the protocol (baseline) and weekly after by cardiac ultrasound in ketamine-anesthetized mice. Cardiotoxicity was defined as a decrease in left ventricular fractional shortening of at least 10% from baseline, an absolute value <50%, and a heart rate >300 BPM. The protocol was reproducible with a 99% success of tumor development, and a >80% mice survival rate. Cardiotoxicity was observed in >90% of the treated mice with tumor and Doxorubicin.