[Expert consensus on adverse reaction management of PAM pathway inhibitors in breast cancer (2026 edition)].

Abstract

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway (PAM pathway) is a crucial signaling network regulating cell proliferation, survival, and metabolism, which plays a central role in the pathogenesis and progression of breast cancer. Targeting the PAM pathway with inhibitors provides a novel precision therapeutic option for cancer patients. However, the broad suppression of physiological PAM pathway functions in normal tissues, combined with the distinct characteristics of their molecular targets, leads to both the uniqueness of adverse reactions associated with these agents and heterogeneity within their safety profiles. Given the complexity of the adverse reaction spectrum and the specialized management requirements for PAM pathway inhibitors, Cancer Drug Clinical Research Committee of China Anti-Cancer Association and Standard Construction Committee of China Anti-Cancer Association jointly convened a multidisciplinary expert panel to develop this consensus. This document systematically synthesizes epidemiological features, pathological mechanisms, and risk factors of PAM pathway inhibitor-associated adverse reactions. It provides clinicians with evidence-based guidance on standardized prevention strategies, early warning systems, assessment frameworks, intervention protocols, and long-term monitoring pathways. The ultimate goals are to maximize medication safety, optimize treatment adherence, and ultimately enhance antitumor efficacy and patient quality of life.

磷脂酰肌醇3激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白（PAM）通路是调控细胞增殖、存活和代谢的关键信号网络，在乳腺癌的发生发展中发挥核心作用。PAM通路抑制剂为乳腺癌患者提供了精准治疗的新选择，然而其对正常组织生理功能的广泛抑制，会伴随一系列不良反应的发生。此外，由于不同PAM通路抑制剂作用靶点各异，不良反应谱也存在显著差异。鉴于PAM通路抑制剂不良反应谱的复杂性和管理的特殊性，中国抗癌协会肿瘤药物临床研究专业委员会和中国抗癌协会标准建设委员会共同制定了PAM通路抑制剂不良反应专家共识，系统梳理PAM通路抑制剂相关不良反应的流行病学特征、病理机制与风险因素，为临床医师提供了规范化的预防、监测、评估、管理、干预策略和方案，以期最大程度保障乳腺癌患者的用药安全，提高治疗依从性，最终提升抗肿瘤治疗效果与患者生存质量。.