中国癌症杂志2026，Vol.36Issue(2)：131-140,10.DOI:10.19401/j.cnki.1007-3639.2026.02.005
2025年HR+/HER2-乳腺癌内分泌治疗研究热点及展望
2025 research hotspots and prospects of endocrine therapy for HR+/HER2-breast cancer
摘要
Abstract
Hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2-)breast cancer is the most common breast cancer subtype,with endocrine therapy as its core treatment modality.In recent years,the treatment paradigm has shifted toward a comprehensive management model characterized by"endocrine therapy as the foundation plus targeted combination therapy for enhanced efficacy".Based on the important research advances in 2025,this paper systematically reviews the evidence-based evidence and clinical decision-making for this breast cancer subtype across different treatment phases by focusing on 10 key hot issues.In the neoadjuvant setting for early-stage disease,endocrine therapy demonstrates comparable efficacy to chemotherapy in specific patient populations.Cyclin-dependent kinase 4/6(CDK4/6)inhibitors combined with endocrine therapy have exhibited notable biological inhibitory effects.Novel agents such as lasofoxifene,giredestrant,antibody-drug conjugates(ADC),and immunotherapies have expanded the preoperative treatment options,though they have not yet reshaped the current treatment landscape.Adjuvant therapy for early-stage disease emphasizes an individualized strategy stratified by recurrence risk.The 15-year follow-up results of the SOFT/TEXT trials have confirmed the long-term benefits of ovarian function suppression(OFS)combined with aromatase inhibitors(AI)in premenopausal patients with intermediate-high risk.Long-term follow-up data of CDK4/6 inhibitors including abemaciclib,ribociclib,and dalpiciclib have established their core role in adjuvant intensification therapy for intermediate-high risk patients.Additionally,the lidERA trial verified that giredestrant,an oral selective estrogen receptor degrader(SERD),is superior to conventional endocrine therapy,thus emerging as a novel option for intermediate-high risk patients.In the first-line treatment of advanced disease,the three major CDK4/6 inhibitors combined with endocrine therapy yield comparable efficacy.Combination regimens containing phosphatidylinositol 3-kinase alpha(PI3Kα)inhibitors bring clinical benefits to patients with PIK3CA mutations who develop endocrine resistance.Circulating tumor DNA(ctDNA)-guided monitoring of ESR1 mutations enables"early identification and timely switching of therapies",facilitating the transition toward dynamic and precision treatment management.In the post-CDK4/6 inhibitor era for second-line treatment of advanced disease,pathway-oriented strategies based on molecular stratification have become the mainstream.Combination regimens with inhibitors targeting the PI3K/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)axis provide effective options for patients with aberrant PAM pathway activation.Oral SERD and their combination strategies represent the key therapeutic direction for patients with ESR1 mutations,while dual PI3K/mTOR inhibitors have achieved new breakthroughs for patients with wild-type PIK3CA.In summary,research advances over the past year have gradually driven the transformation of HR+/HER2-breast cancer treatment toward precision and dynamism.With the discovery of more therapeutic targets and the development of novel agents in the future,the individualized treatment system will be continuously refined,bringing more durable disease control and long-term survival benefits to patients.关键词
激素受体阳性/乳腺癌/CDK4/6抑制剂/循环肿瘤DNA/ESR1突变/PIK3CA突变/口服SERDKey words
Hormone receptor-positive/Breast cancer/CDK4/6 inhibitor/Circulating tumor DNA/ESR1 mutation/PIK3CA mutation/Oral SERD分类
医药卫生引用本文复制引用
张蓝心,高子慧,李宁,韩佳鹏,赵作伟,李曼..2025年HR+/HER2-乳腺癌内分泌治疗研究热点及展望[J].中国癌症杂志,2026,36(2):131-140,10.基金项目
国家自然科学基金(82473449,82503885,82274296) （82473449,82503885,82274296）
辽宁省自然科学基金博士启动项目(2025-BS-0689) （2025-BS-0689）
中国HR+/HER2-早期乳腺癌优化诊治研究基金(EBC-L005) （EBC-L005）
北京希思科肿瘤研究项目(Y-Gilead2024-ZD-0049) （Y-Gilead2024-ZD-0049）
大连医科大学附属第二医院"1+X"大型队列研究(2022DXDL03). National Natural Science Foundation of China(82473449,82503885,82274296) （2022DXDL03）
Liaoning Provincial Natural Science Foundation for Doctoral Start-up Projects(2025-BS-0689) （2025-BS-0689）
China Research Fund for Optimal Diagnosis and Treatment of HR+/HER2-Early Breast Cancer(Grant No.EBC-L005) （Grant No.EBC-L005）
Beijing CSCO Cancer Research Project(Y-Gilead2024-ZD-0049) （Y-Gilead2024-ZD-0049）
The"1+X"Large Cohort Study of The Second Affiliated Hospital of Dalian Medical University(2022 DXDL03). （2022 DXDL03）
