Today, breast cancer (BC) is the most commonly diagnosed cancer in women. HER2-positive BC is one of the BC subtypes which is characterized by presence/absence of estrogen and progesterone receptors and, most of all, overexpression of the human epidermal growth factor receptor-2 (HER2) determining both the disease prognosis and treatment strategy. Unfortunately, actual therapy of early HER2-positive cancer considering all the "targets" does not fully achieve all the goals, the main of which are a pathological complete response and decreased incidence of cardiac complications after the treatment. This determines the relevance of searching for all the possible significant predictive factors of response to the drug therapy, reduced risk of cardiac complications and pharmacoeconomical justification of the therapy regimens. A presented literature review identifies the most important and relevant issues associated with neoadjuvant drug therapy of luminal/non-luminal HER2-positive BC along with possible solutions. © 2024 Meditsina-Inform LLC. All rights reserved.