CDK4/6抑制剂后时代下的乳腺癌精准诊疗  

Precision diagnosis and treatment of breast cancer in the post-CDK4/6 inhibitor era

作　　者：李彬 陶中华 胡夕春 LI Bin;TAO Zhonghua;HU Xichun(Department of Medical Oncology,Fudan University Shanghai Cancer Center,Department of Oncology,Shanghai Medical College,Fudan University,Shanghai 200032,China;Committee of Breast Cancer Society,Shanghai Anti-Cancer Association,Shanghai 200032,China;Committee of Clinical Research on Anticancer Drugs,Shanghai Anti-Cancer Association,Shanghai 200032,China)

机构地区：[1]复旦大学附属肿瘤医院肿瘤内科,复旦大学上海医学院肿瘤学系,上海200032 [2]上海市抗癌协会乳腺癌专业委员会,上海200032 [3]上海市抗癌协会肿瘤药物临床研究专业委员会,上海200032

出　　处：《中国癌症杂志》2025年第3期273-282,共10页China Oncology

基　　金：国家自然科学基金(82473071);上海市抗癌协会“翱翔”计划(SACA-AX202402)。

摘　　要：细胞周期蛋白依赖性激酶(cyclin-dependent kinase,CDK)4/6抑制剂联合内分泌治疗是激素受体阳性、人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)阴性晚期乳腺癌患者的标准一线治疗方案。CDK4/6抑制剂的出现使患者预后得到进一步提升,但也带来了新的临床问题,如许多患者在治疗后仍会出现进展和耐药,而目前对于CDK4/6抑制剂联合内分泌治疗进展的患者缺乏标准的后续治疗方案。内分泌治疗药物耐药通过雌激素受体(estrogen receptor,ESR)依赖或非依赖性途径导致肿瘤进展,新型内分泌治疗药物可能使携带ESR1基因突变的乳腺癌患者获益。携带磷脂酰肌醇3-激酶(phosphoinositide 3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)/哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)通路变异的患者可能对该通路的靶向抑制剂治疗敏感。此外,已获批或正在早期开发的新型抗体药物偶联物(antibody-drug conjugate,ADC)、免疫联合治疗方案及新型细胞周期特异性药物也展现出积极的抗肿瘤活性。以精准药物为基础的组合方案在丰富临床选择的同时,也让个体化治疗成为可能,基于生物标志物的精准治疗策略成为CDK4/6抑制剂后时代的重要发展方向。Cyclin-dependent kinase(CDK)4/6 inhibitors plus endocrine therapy represents the standard first-line treatment for patients with hormone receptor-positive,human epidermal growth factor receptor 2(HER2)-negative advanced breast cancer.The introduction of CDK4/6 inhibitors has significantly improved the prognosis of breast cancer patients.However,it has also brought new clinical challenges,such as disease progression and treatment resistance in many patients.Currently,there is a lack of standardized subsequent treatment options for patients whose disease progresses after CDK4/6 inhibitor combined with endocrine therapy.Endocrine therapy resistance can lead to tumor progression through estrogen receptor(ESR)-dependent or ESR-independent pathways.Novel endocrine agents have the potential to benefit breast cancer patients harboring ESR1 mutations.Patients with alterations in the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway may be particularly sensitive to targeted inhibitors of this pathway.Furthermore,newly approved or investigational antibody-drug conjugate(ADC),immunotherapy-based combinations,and novel cell cycle inhibitors have demonstrated promising anti-tumor activities.Precision medicine-based combination strategies not only expand clinical treatment options but also enable physicians to make personalized treatment decisions for patients.Biomarker-driven precision therapeutic strategies have emerged as a critical area of treatment development in the post-CDK4/6 inhibitor era.

关 键 词：激素受体阳性晚期乳腺癌 细胞周期蛋白依赖性激酶4和6抑制剂 精准诊疗 内分泌治疗 靶向治疗 抗体药物偶联物 

分 类 号：R737.9[医药卫生—肿瘤]