The role of CDK4/6 inhibitors in the treatment of luminal HER2/neu-negative early breast cancer

<jats:p> Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have become an integral component of both international and national treatment guidelines for patients with hormone receptor-positive (HR-positive), HER2-negative metastatic breast cancer. This review aimed to summarize current evidence on the efficacy of palbociclib, ribociclib, and abemaciclib in the metastatic, adjuvant, and neoadjuvant treatment settings for luminal HER2-negative breast cancer. A literature search was conducted in the PubMed/ MEDLINE, <jats:ext-link>eLIBRARY.ru,</jats:ext-link> and <jats:ext-link>cyberleninka.ru</jats:ext-link> databases covering the period from January 2000 to December 2025. The search strategy included the following keywords: “CDK4/6 inhibitors”, “palbociclib”, “ribociclib”, “abemaciclib”, “hormone receptor-positive breast cancer”, “HER2-negative breast cancer”, “early breast cancer”, as well as their Russian-language equivalents. Eligible publications included phase II–III randomized controlled trials, prospective and retrospective cohort studies, meta-analyses, clinical practice guidelines, and narrative reviews. Conference abstracts and publications in languages other than English or Russian were excluded. A total of 49 publications were included in the qualitative synthesis; no quantitative meta-analysis was performed. Five references were used for the Introduction, whereas 12, 11, and 13 publications informed the sections on metastatic, adjuvant, and neoadjuvant therapy, respectively. The remaining studies were included in the comparative summary table of clinical trials. Evidence from pivotal clinical trials, including PALOMA-1/2/3, MONARCH-2/3, MONALEESA-2/3/7, monarchE, NATALEE, PALLAS, PENELOPE-B, NeoPAL, NeoPalAna, and CORALLEEN, demonstrates that CDK4/6 inhibitors provide clinically meaningful and statistically significant improvements in progression-free, disease-free, and overall survival in selected patient populations with both advanced and early breast cancer. Future research should focus on identifying predictive biomarkers of treatment response and optimizing the sequencing of CDK4/6 inhibitors across different stages of the disease. </jats:p>