The challenge of evaluating the efficacy of neoadjuvant endocrine therapy in breast cancer and potential solutions: a literature review

Abstract

Hormone receptor–positive (HR+) breast cancer is the most common subtype of the disease and is characterized by significant heterogeneity in its clinical course and response to therapy. Adjuvant endocrine therapy with aromatase inhibitors represents a highly effective alternative to chemotherapy in postmenopausal patients, demonstrating comparable clinical response rates with lower toxicity. Despite the proven efficacy of neoadjuvant endocrine therapy (NET) in reducing tumor volume and increasing the rate of breast-conserving surgery, the rate of pathological complete response (pCR) in HR+/HER2– breast cancer remains low (10–20%). Predicting which patients with breast cancer will respond to treatment remains a challenging task. This limited predictive capability often leads to the use of multiple lines of therapy in the search for an option that will provide a therapeutic response. In this context, biomarkers of treatment efficacy, including Ki‑67 index dynamics, the Preoperative Endocrine Prognostic Index (PEPI), and multigene panels, are particularly important. In recent years, the molecular mechanisms of endocrine resistance have been actively investigated, including ESR1 gene mutations, activation of the PI3K/AKT/mTOR signaling pathways, and alterations in cell cycle regulation. Post-transcriptional regulation of gene expression involving microRNAs plays a significant role in these processes. Specific microRNAs (in particular, miR‑221/222, miR‑21, and miR‑342) have demonstrated an association with sensitive ty or resistance to endocrine therapy and are considered potential predictive biomarkers. Of particular interest is the analysis of circulating microRNAs, which may be used as minimally invasive markers for dynamic monitoring of treatment response and early detection of endocrine resistance. Thus, the integration of clinical, morphological, and molecular parameters, including microRNA profiling, represents a promising approach for personalizing neoadjuvant endocrine therapy and optimizing treatment strategies in patients with HR+ breast cancer.