INTRODUCTION AND OBJECTIVES: The cells of the immune system influence both the control and the development of cancer. The knowledge of the leukocyte infiltrate allows to understand and evaluate the efficiency of several antitumor therapies, allowing the optimization of existing therapeutic approaches and the development of new therapies. The use of murine models allows us to review the complexity of human tumor development and microenvironment. In this project, a transgenic murine model that develops breast cancer, the PyMT mice, will be used. Tumor development in these animals is histologically and genetically comparable to breast cancer in humans, being able to reproduce many forms of this disease. Breast cancer is the leading cause of cancer death among women worldwide. Currently, anthracyclines followed by taxane are used for the chemotherapy treatment of breast cancer, but there is no biological basis to support this order, and this sequence was established in the order in which these chemotherapeutic drugs were started. NeoSamba: Randomized phase II trial study (INCA) demonstrated that there was better overall and disease-free survival in patients treated with the reverse order of chemotherapy blocks: taxane followed by anthracyclines. Based on the rationale of this protocol, the impacts of neoadjuvant treatment with combinations of anthracyclines (5-fluorouracil, doxorubicin and cyclophosphamide - FAC) will be inferred followed by taxane (docetaxel) and the reverse order (taxane followed by FAC) on the leukocyte infiltrate in the murine model PyMT.
MATERIAL AND METHODS: In this study, PyMT mice will be treated once a week, with an interval of one week between the chemotherapy arms. Each arm will last for 3 weeks. After treatment, tumor dissociation will be performed and the infiltrate will be analyzed by flow cytometry and RNA sequencing (RNA-Seq).
RESULTS AND CONCLUSION: As initial results, we made tumor growth curves, defining the sizes of the tumors to be collected for the analysis and toxicity tests, setting the doses for chemotherapy treatments. As a next step, we will start treating the animals and assess their leukocyte infiltrate qualitatively and quantitatively after each of the chemotherapy blocks, after the complete sequence of therapy in the standard order and also in the inverted order. In this way, we hope to characterize the impact of different chemotherapeutic regimes on the tumor immune response.