Breast cancer resistance to chemotherapy: When should we suspect it and how can we prevent it?

Chemotherapy is an essential treatment for breast cancer, inducing cancer cell death. However, chemoresistance is a problem that limits the effectiveness of chemotherapy. Many factors influence chemoresistance, including drug inactivation, changes in drug targets, overexpression of ABC transporters, epithelial-to-mesenchymal transitions, apoptotic dysregulation, and cancer stem cells. The effectiveness of chemotherapy can be assessed clinically and pathologically. Clinical response evaluation is based on physical examination or imaging (mammography, ultrasonography, computed tomography scan, or magnetic resonance imaging) and includes tumor size changes after chemotherapy. Pathological response evaluation is a method based on tumor residues in histopathological preparations. We should be suspicious of chemoresistance if there are no significant changes clinically according to the Response Evaluation Criteria in Solid Tumors and World Health Organization criteria or pathological changes according to the Miller and Payne criteria, especially after 2–3 cycles of chemotherapy treatments. Chemoresistance is mostly detected after the administration of chemotherapy drugs. No reliable parameters or biomarkers can predict chemotherapy responses appropriately and effectively. Well-known pa- rameters such as cancer type, grade, subtype, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki-67, and MDR-1/P-gP have been used for selecting chemotherapy regimens. Some new methods for predicting chemoresistance include chemosensitivity and chemoresistance assays, multigene ex- pressions, and positron emission tomography assays. The latest approaches are based on evaluation of molecular processes and the metabolic activity of cancer cells. Some methods for preventing chemoresistance include using the right regimen, using some combination of chemotherapy methods, conducting adequate monitoring, and using drugs that could prevent the emergence of multidrug resistance.