Molecular shifts in breast cancer following neoadjuvant chemotherapy: a prospective study and review of literature

Abstract

Background: Standard clinical guidelines recommend evaluating Estrogen & progesterone Receptor (ER, PR), Human epidermal growth factor receptor-2 (HER-2), and Ki-67 in breast cancer biopsy samples. This study investigates the changes in molecular subtype following neoadjuvant chemotherapy (NACT) in breast cancer patients. Methods: Patients aged 18 to 65 years who underwent core needle biopsy before NACT and received at least four chemotherapy cycles were included in the study. Patients with inflammatory breast cancer, de novo metastatic or bilateral breast cancer, pregnancy, lactation, prior endocrine/radiation therapy, or achieved pathological complete response (pCR) were excluded. Molecular profiles (ER, PR, HER-2, Ki-67) were analyzed pre- and post-NACT. Results: The study involved 100 breast cancer patients with a median age of 51.78 years. 47% of patients underwent breast-conserving surgery (BCS), while 53% underwent modified radical mastectomy (MRM). Seventy-six percent of patients had tumors larger than 5 cm, and 72% presented with axillary lymph node metastasis. Initially, 90% and 89% of patients were ER, and PR positive, respectively, which decreased to 81% and 75% post-surgery. Ki67 expression showed a significant reduction following chemotherapy. Larger tumors and lymph node-positivity had significant changes in molecular subtypes. Conclusion: The study revealed significant alterations in ER, PR, HER-2, and Ki-67 levels post-NACT, prompting reassessment for tailored therapy. © 2025 Informa UK Limited, trading as Taylor & Francis Group.