Implication of tumor microenvironment in the resistance to chemotherapy in breast cancer patients

Chemotherapy is a cornerstone treatment in patients with early breast cancer. Although some cancer cell-related predictors are emerging, the indications of chemotherapy and the choice of chemotherapy regimen are not individualized enough, emphasizing the need for new predictors. This review will summarize recent advances concerning the implication of tumor microenvironment in the response to chemotherapy.

In recent years, some data have emerged suggesting that microenvironment could be involved in chemotherapy efficacy. The infiltration of tumor by lymphocytes has been highly correlated with the sensitivity to chemotherapy. These data are consistent with the discovery that anthracyclines could induce immune activation through immunogenic cell death. At the opposite, gene expression analyses have suggested that a stroma signature could predict resistance to neoadjuvant chemotherapy. Finally, chemotherapy has been shown to induce a spike of progenitors for endothelial cells, a mechanism that in turns mediates angiogenesis repopulation.

Preliminary data from pioneer studies suggest that tumor microenvironment could be involved in chemotherapy sensitivity and resistance. Such knowledge could generate two advances: simple predictors for chemotherapy efficacy based on pathology could be generated and strategies that aim at reversing drug resistance could be developed.