Tyrosine kinase inhibitors in breast cancer (Review).

Anti-epidermal growth factor receptor (EGFR)-targeted therapy has been intensely researched in the last years, motivated by the favorable results obtained with monoclonal antibodies in HER2-enriched breast cancer (BC) patients. Most researched alternatives of anti-EGFR agents were tyrosine kinase inhibitors (TKIs) and monoclonal antibodies. However, excluding monoclonal antibodies trastuzumab and pertuzumab, the remaining anti-EGFR molecules have exhibited disappointing results, due to the lack of specificity and frequent adverse side effects. TKIs have several advantages, including reduced cardiotoxicity, oral administration and favorable penetration of blood-brain barrier for brain metastatic BC. Lapatinib and neratinib and recently pyrotinib (approved only in China) are the only TKIs from dozens of molecules researched over the years that were approved to be used in clinical practice with limited indications, in a subset of BC patients, single or in combination with other chemotherapy or hormonal therapeutic agents. Improved identification of BC subtypes and improved characterization of aggressive forms (triple negative BC or inflammatory BC) should lead to advancements in shaping of targeted agents to improve the outcome of patients.