2025年HR+/HER2-乳腺癌内分泌治疗研究热点及展望OA

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.