Abstract
Breast cancer (BC) occupies a leading position among all malignant neoplasms in women worldwide and is the 4th deadliest. Most cases are diagnosed in stages I–III. Among the molecular biological variants, luminal HER2 negative (HER2-) prevails, accounting for 70–75%. Currently, therapies combining surgery with chemotherapy and, more rarely, radiation therapy, followed by adjuvant hormone therapy for up to 10 years, are a standard of care in BC. The goal of these regimens is the prevention of early recurrence in patients in the high-risk group with a primary hormone-resistant tumor. However, at the end of treatment, it occurs in 27–57% of patients with stage II–III breast cancer. For its prevention in early HR-positive (HR+) HER2- BC, an innovative class of drugs, cyclin-dependent kinase 4/6 inhibitors, is used combined with hormone therapy (aromatase inhibitors, anti-estrogens, gonadotropin-releasing hormone agonists), which is the subject of a randomized phase III NATALEE study evaluating the efficacy and safety of ribociclib in combination with endocrine therapy in early non-metastatic BC. The study enrolled patients with stage II–III breast cancer, including those with N0. Patients of the study group received ribociclib at a dose of 400 mg/day for 21 days in combination with aromatase inhibitors, and in the control group, only aromatase inhibitors. The median follow-up was 34 months. Three-year survival without invasive disease was 90.7% in the ribociclib group and 87.6% in controls. The risk of distant metastasis and invasive diseases was reduced by 25.1% in the ribociclib group. Therefore, ribociclib tended to improve overall survival. The initial dose of 400 mg/day reduced the incidence of adverse events; the most common were neutropenia (62.5%), arthralgia (37.3%) and hepatic toxicity (26.4%). The most common reasons for discontinuing ribociclib were hepatic toxicity (8.9%) and arthralgia (1.3%). The results demonstrate a statistical and clinical superiority of ribociclib in combination with hormone therapy in the treatment of early HR+ HER2- breast cancer with a high risk of recurrence.