Prognostically unfavorable types of breast cancer — triple-negative, Her2/neu-positive, and luminal B Her2/neu-positive — are characterized by aggressive progression and a high risk of recurrence. Molecular-genetic and immunohistochemical methods allow clarification of the biological heterogeneity of these forms and the identification of therapeutic targets. This article reviews the epidemiology, pathogenesis, hereditary mutations, and current approaches to systemic therapy. Particular attention is given to the role of neoadjuvant drug treatment and the achievement of a complete pathological response as the basis for de-escalation of surgical management. The possibilities of breast-conserving treatment in aggressive types of breast cancer are analyzed. The role of radiotherapy in improving local control and in the individualization of treatment is also discussed. The review emphasizes the necessity of an individualized approach at all stages of management of “aggressive” forms of breast cancer, including surgical intervention guided by molecular tumor characteristics and clinical response.