An ODE Model of A Breast Cancer Tumor: HER2+

Abstract

We are developing an ODE model of a human epidermal growth factor receptor 2-positive (HER2+) breast cancer tumor that accounts, in a simplified way, for the tumor structure and interaction with the immune system. Mounting empirical research suggests that the tumor stroma or tumor interface zone is a critical determinate of the propensity of the cancer to invade and/or metastasize. Likewise, there is increasing interest in cancer therapies that encourage the immune system to target and destroy cancer cells. We describe tumor growth while accounting for the interface zone and the interaction between the tumor and natural killer cells (NK cells). Interactions between HER2+ breast cancer tumor cells and NK cells can be influenced by the antibody drug trastuzumab, and we use our model to investigate tumor growth (i) in isolation, and (ii) in the presence of NK cells and trastuzumab. Model predictions are compared to empirical data on tumor growth. We found that increasing the cytotoxicity of patrolling NK cells may be insufficient for the control of highly aggressive tumors (those with very fast proliferation or high density). However, if healthy tissue has high levels of patrolling cytotoxic NK cells, then the tumor cannot exist.