Mechanisms behind prometastatic changes induced by neoadjuvant chemotherapy in the breast cancer microenvironment

Abstract

Vladimir M Perelmuter,1 Liubov A Tashireva,1 Olga E Savelieva,1 Evgeny V Denisov1,2, Evgeniya V Kaigorodova1,3, Marina V Zavyalova1,4, Nadezhda V Cherdyntseva1,21Cancer Research Institute, Tomsk National Research Medical Center, Tomsk 634050, Russia; 2Laboratory for Translational Cellular and Molecular Biomedicine, Tomsk State University, Tomsk 634050, Russia; 3Department of Biochemistry, Siberian State Medical University, Tomsk 634055, Russia; 4Department of Pathological Anatomy, Siberian State Medical University, Tomsk 634055, RussiaAbstract: Chemotherapy, along with surgery and radiotherapy, is a key treatment option for malignant tumors. Neoadjuvant chemotherapy (NACT) reduces the tumor size and enables total tumor resection. In addition, NACT is believed to be more effective in destroying micrometastases than the same chemotherapy performed after surgery. To date, various NACT regimens have been tested and implemented, which provide a favorable outcome in primary tumors and reduce the risk of progression. However, there is increasing evidence of the NACT ability to increase the risk of cancer progression. This review discusses potential mechanisms by which NACT promotes distant metastasis of breast cancer through changes in the microenvironment of tumor cells. We describe prometastatic NACT-mediated changes in angiogenesis, immuno-inflammatory reactions in the stroma, intravasation, and amount of circulating tumor cells. The role of NACT-related cellular stress in cancer metastasis is also discussed.Keywords: breast cancer, neoadjuvant chemotherapy, microenvironment, intravasation, metastasis, stress

Keywords

• breast cancer
• neoadjuvant chemotherapy
• microenvironment
• intravasation
• metastasis
• stress.