Salahi-Niri Aryan, Zarand Paniz, Shojaeian Fatemeh, Mansouri Negar, Yazdani Omid, Esbati Romina, Safavi-Naini Seyed Amir Ahmad, Jahanbin Behnaz
Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research, Institute for Gastroenterology and Liver Diseases Shahid Beheshti University of Medical Sciences Tehran Iran.
Sidney Kimmel Comprehensive Cancer Research Center Johns Hopkins School of Medicine Baltimore Maryland USA.
Health Sci Rep. 2025 Apr 8;8(4):e70626. doi: 10.1002/hsr2.70626. eCollection 2025 Apr.
Breast cancer is the most common cancer and a leading cause of cancer-related death among women globally. Determining which patients will benefit from chemotherapy remains challenging. Proliferative markers such as Ki-67, mini chromosome maintenance (MCM) proteins, and proliferating cell nuclear antigen (PCNA) offer valuable insights into tumor growth and treatment response. This review evaluates their clinical roles, with a focus on chemotherapy implications and emerging digital pathology techniques for marker quantification.
A narrative review was conducted by searching PubMed, Scopus, and Google Scholar for studies related to Ki-67, MCM, PCNA, breast cancer, and chemotherapy. Studies were thematically categorized into five areas. A bibliometric analysis of publications from 2000 to April 2023 was performed using the Bibliometrix R package and VOSviewer to assess research trends and thematic evolution.
Eighty studies were included in the narrative synthesis. Ki-67 is the most commonly used marker, particularly useful in predicting response to neoadjuvant chemotherapy (NAC). MCM proteins show promise for identifying proliferative potential across tumor grades, while PCNA is associated with aggressive tumor features and poor prognosis. Post-chemotherapy changes in Ki-67 levels are linked to survival outcomes. Bibliometric analysis revealed a shift in research focus from basic mechanisms to clinical applications and digital quantification.
Proliferative markers play an essential role in breast cancer management. Ki-67 remains a key predictor of chemotherapy response, while MCM and PCNA offer complementary prognostic insights. Integration of these markers with digital pathology and AI-driven tools may enhance diagnostic accuracy and personalized treatment strategies. Standardization of assessment methods is crucial for broader clinical application.
乳腺癌是全球女性中最常见的癌症，也是癌症相关死亡的主要原因。确定哪些患者将从化疗中获益仍然具有挑战性。增殖标志物，如Ki-67、微小染色体维持（MCM）蛋白和增殖细胞核抗原（PCNA），为肿瘤生长和治疗反应提供了有价值的见解。本综述评估了它们的临床作用，重点关注化疗意义以及用于标志物定量的新兴数字病理学技术。
通过检索PubMed、Scopus和谷歌学术搜索与Ki-67、MCM、PCNA、乳腺癌和化疗相关的研究，进行了一项叙述性综述。研究按主题分为五个领域。使用Bibliometrix R包和VOSviewer对2000年至2023年4月的出版物进行文献计量分析，以评估研究趋势和主题演变。
叙述性综合分析纳入了80项研究。Ki-67是最常用的标志物，在预测新辅助化疗（NAC）反应方面特别有用。MCM蛋白有望识别不同肿瘤分级的增殖潜力，而PCNA与侵袭性肿瘤特征和不良预后相关。化疗后Ki-67水平的变化与生存结果相关。文献计量分析显示研究重点从基本机制转向临床应用和数字定量。
增殖标志物在乳腺癌管理中起着至关重要的作用。Ki-67仍然是化疗反应的关键预测指标，而MCM和PCNA提供了互补的预后见解。将这些标志物与数字病理学和人工智能驱动的工具相结合，可能会提高诊断准确性和个性化治疗策略。评估方法的标准化对于更广泛的临床应用至关重要。
