

浏览全部资源
扫码关注微信
解放军总医院第五医学中心肿瘤医学部,北京 100071
Received:31 December 2024,
Revised:2025-01-30,
Published:28 February 2025
移动端阅览
Song WU, Yang YUAN, Zefei JIANG. Important clinical studies that changed the clinical practice of advanced breast cancer in 2024[J]. China Oncology, 2025, 35(2): 186-194.
Song WU, Yang YUAN, Zefei JIANG. Important clinical studies that changed the clinical practice of advanced breast cancer in 2024[J]. China Oncology, 2025, 35(2): 186-194. DOI: 10.19401/j.cnki.1007-3639.2025.02.005.
随着分子生物学研究的深入和精准医学的发展,晚期乳腺癌的治疗手段日益丰富。2024年,不同分子亚型晚期乳腺癌治疗领域的多项研究均取得了进展。其中,内分泌治疗联合细胞周期蛋白依赖性激酶4和6(cyclin-dependent kinase 4/6,CDK4/6)抑制剂已成为激素受体阳性晚期乳腺癌的一线标准治疗方案。氟维司群联合阿贝西利可作为CDK4/6抑制剂治疗失败后的治疗选择。而对于伴有AKT信号转导通路异常的患者,氟维司群联合AKT抑制剂capivasertib可为患者带来显著的远期生存获益。德曲妥珠单抗(trastuzumab deruxtecan,T-DXd)则为人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)超低表达人群提供了新的治疗选择。对于HER2阳性晚期乳腺癌,紫杉类药物联合曲妥珠单抗与帕妥珠单抗或吡咯替尼仍是目前曲妥珠单抗敏感人群的标准一线治疗方案。DESTINY-Breast07研究评估了T-DXd用于一线治疗的可行性,结果显示,无论是单药或联合帕妥珠单抗,其无进展生存率(progression-free survival,PFS)均不劣于既往研究中的标准治疗方案。针对HER2阳性脑转移患者,PERMEATE研究的更新数据显示,吡咯替尼联合卡培他滨方案可带来总生存期获益。DESTINY-Breast12研究表明,T-DXd对全身和颅内病灶的抗肿瘤活性相似,可作为HER2阳性脑转移患者的有效治疗选择。晚期三阴性乳腺癌(triple-negative advanced breast cancer,TNBC)的治疗策略正在从传统化疗转向以化疗联合免疫治疗以及抗体药物偶联物(antibody-drug conjugate,ADC)为主的治疗模式。TORCHLIGHT研究显示,化疗联合免疫检查点抑制剂特瑞普利单抗可改善晚期TNBC患者的预后。NCC2167研究表明,当化疗与免疫治疗联合使用时,节拍式化疗相比传统方式具有高疗效及低毒性的特点。本文对上述2024年晚期乳腺癌领域的重要研究进展进行梳理,并结合相关研究数据,总结了晚期乳腺癌患者管理和治疗决策的临床经验,以供同行参考。展望未来,后续临床研究需重点关注患者的个体差异、肿瘤的异质性以及治疗耐药性问题,以提升晚期乳腺癌的治疗效果和患者的生活质量。
With advancements in molecular biology research and precision medicine
treatment options for advanced breast cancer have become increasingly diverse. In 2024
significant research progress has been achieved across different molecular subtypes of advanced breast cancer. Endocrine therapy combined with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has become the standard first-line treatment for hormone receptor-positive advanced breast cancer. Fulvestrant combined with abemaciclib serves as a treatment option after failure in CDK4/6 inhibitors. For patients with mutations in the AKT pathway
fulvestrant combined with the AKT inhibitor capivasertib provides significant long-term survival benefits. Trastuzumab deruxtecan (T-DXd) has emerged as a novel treatment option for patients with HER2 ultra-low expression. For HER2-positive advanced breast cancer
taxanes combined with trastuzumab and pertuzumab or pyrotinib remain the standard first-line treatments for trastuzumab-sensitive patients. The DESTINY-Breast07 trial evaluated the feasibility of using T-DXd as a first-line treatment
showing that whether used as monotherapy or in combination with pertuzumab
progression-free survival (PFS) was non-inferior to standard regimens reported in previous studies. For HER2-positive patients with brain metastases
updated results from the PERMEATE trial indicated that the combination of pyrotinib and capecitabine could provide overall survival benefits. The DESTINY-Breast12 trial demonstrated that T-DXd had similar antitumor activity against systemic and intracranial lesions
making it an effective treatment option for HER2-positive patients with brain metastases. Treatment strategies for advanced triple-negative breast cancer (TNBC) are shifting from conventional chemotherapy to regimens centered on chemotherapy combined with immunotherapy and antibody-drug conjugates (ADCs). The TORCHLIGHT trial showed that chemotherapy combined with the immune checkpoint inhibitor toripalimab improved the prognosis of patients with advanced TNBC. The NCC2167 trial found that when chemotherapy was combined with immunotherapy
metronomic chemotherapy offered superior efficacy and lower toxicity compared to conventional approaches. This article reviewed the significant research progress in advanced breast cancer in 2024. By summarizing related research data
it provides insights into the clinical experience of managing and making treatment decisions for patients with advanced breast cancer
serving as a reference for peers. Looking ahead
future clinical research should focus on individual differences among patients
tumor heterogeneity
and treatment resistance
aiming to improve treatment outcomes and the quality of life for patients with advanced breast cancer.
JOHNSTON S , MARTIN M , DI LEO A , et al . MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer [J ] . NPJ Breast Cancer , 2019 , 5 : 5 . DOI: 10.1038/s41523-018-0097-z http://doi.org/10.1038/s41523-018-0097-z
ZHANG P , ZHANG Q Y , TONG Z S , et al . Dalpiciclib plus letrozole or anastrozole versus placebo plus letrozole or anastrozole as first-line treatment in patients with hormone receptor-positive, HER2-negative advanced breast cancer (DAWNA-2): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial [J ] . Lancet Oncol , 2023 , 24 ( 6 ): 646 - 657 .
HORTOBAGYI G N , STEMMER S M , BURRIS H A , et al . Overall survival with ribociclib plus letrozole in advanced breast cancer [J ] . N Engl J Med , 2022 , 386 ( 10 ): 942 - 950 .
LU Y S , BIN MOHD MAHIDIN E I , AZIM H , et al . Final results of RIGHT choice: ribociclib plus endocrine therapy versus combination chemotherapy in premenopausal women with clinically aggressive hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer [J ] . J Clin Oncol , 2024 , 42 ( 23 ): 2812 - 2821 .
ZHANG Q Y , SUN T , YIN Y M , et al . MONARCH plus: abemaciclib plus endocrine therapy in women with HR + /HER2 - advanced breast cancer: the multinational randomized phase Ⅲ study [J ] . Ther Adv Med Oncol , 2020 , 12 : 1758835920963925.
TURNER N C , IM S A , SAURA C , et al . Inavolisib-based therapy in PIK3CA -mutated advanced breast cancer [J ] . N Engl J Med , 2024 , 391 ( 17 ): 1584 - 1596 .
KALINSKY K , BIANCHINI G , HAMILTON E P , et al . Abemaciclib plus fulvestrant vs fulvestrant alone for HR + , HER2 - advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: primary outcome of the phase 3 postMONARCH trial [J ] . J Clin Oncol , 2024 , 42 ( 17_suppl ): LBA1001 .
TURNER N C , OLIVEIRA M , HOWELL S J , et al . Capivasertib in hormone receptor-positive advanced breast cancer [J ] . N Engl J Med , 2023 , 388 ( 22 ): 2058 - 2070 .
RUGO H S , OLIVEIRA M , HOWELL S J , et al . Capiva sertib and fulvestrant (F) for patients (pts) with aromatase inhibitor (AI)-resistant HR + /HER2 - advanced breast cancer (ABC): second progression-free survival (PFS2) and time to first subsequent chemotherapy (TFSC) in the CAPItello-291 trial [J ] . ESMO Open , 2024 , 9 : 103205 .
MODI S N , JACOT W , YAMASHITA T , et al . Trastuzumab deruxtecan in previously treated HER2 - low advanced breast cancer [J ] . N Engl J Med , 2022 , 387 ( 1 ): 9 - 20 .
BARDIA A , HU X C , DENT R , et al . Trastuzumab deruxtecan after endocrine therapy in metastatic breast cancer [J ] . N Engl J Med , 2024 , 391 ( 22 ): 2110 - 2122 .
BARDIA A , JHAVERI K , IM S A , et al . Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer: primary results from TROPION-Breast01 [J ] . J Clin Oncol , 2024 : JCO2400920.
JHAVERI K L , NEVEN P , CASALNUOVO M L , et al . Imlunestrant with or without abemaciclib in advanced breast cancer [J ] . N Engl J Med , 2024 .
SWAIN S M , MILES D , KIM S B , et al . Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study [J ] . Lancet Oncol , 2020 , 21 ( 4 ): 519 - 530 . DOI: S1470-2045(19)30863-0 http://doi.org/S1470-2045(19)30863-0
MA F , YAN M , LI W , et al . Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial [J ] . BMJ , 2023 , 383 : e076065 .
YAN M , BIAN L , HU X C , et al . Pyrotinib plus capecitabine for human epidermal growth factor receptor 2-positive metastatic breast cancer after trastuzumab and taxanes (PHENIX): a randomized, double-blind, placebo-controlled phase 3 study [J ] . Transl Breast Cancer Res , 2020 , 1 : 13 .
XU B H , YAN M , MA F , et al . Pyrotinib plus capecitabine versus lapatinib plus capecitabine for the treatment of HER2-positive metastatic breast cancer (PHOEBE): a multicentre, open-label, randomised, controlled, phase 3 trial [J ] . Lancet Oncol , 2021 , 22 ( 3 ): 351 - 360 . DOI: 10.1016/S1470-2045(20)30702-6 http://doi.org/10.1016/S1470-2045(20)30702-6
CORTÉS J , KIM S B , CHUNG W P , et al . Trastuzumab deruxtecan versus trastuzumab emtansine for breast cancer [J ] . N Engl J Med , 2022 , 386 ( 12 ): 1143 - 1154 .
ANDRÉ F , PARK Y H , KIM S B , et al . Trastuzumab deruxtecan versus treatment of physician’s choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): a randomised, open-label, multicentre, phase 3 trial [J ] . Lancet , 2023 , 401 ( 10390 ): 1773 - 1785 .
ANDRE F , HAMILTON E P , LOI S , et al . DESTINY-Breast07: dose-expansion interim analysis of T-DXd monotherapy and T-DXd+pertuzumab in patients with previously untreated HER2 + mBC [J ] . J Clin Oncol , 2024 , 42 ( 16_suppl ): 1009 .
DEBUSK K , IKE C , LINDEGGER N , et al . Real-world outcomes among patients with HER2 + metastatic breast cancer with brain metastases [J ] . J Manag Care Spec Pharm , 2022 , 28 ( 6 ): 657 - 666 .
YAN M , OUYANG Q C , SUN T , et al . Pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer and brain metastases: 3-year follow-up results from the phase 2 PERMEATE trial [J ] . J Clin Oncol , 2023 , 41 ( 16_suppl ): 1048 .
YAN M , OUYANG Q C , SUN T , et al . Pyrotinib plus capecitabine for patients with HER2-positive metastatic breast cancer and brain metastases (PERMEATE trial): overall survival results from a multicenter, single-arm, two-cohort, phase 2 trial [J ] . EClinicalMedicine , 2024 , 76 : 102837 .
YANG Z Z , MENG J , MEI X , et al . Brain radiotherapy with pyrotinib and capecitabine in patients with ERBB2-positive advanced breast cancer and brain metastases: a nonrandomized phase 2 trial [J ] . JAMA Oncol , 2024 , 10 ( 3 ): 335 - 341 .
HURVITZ S A , MODI S , LI W , et al . 377O A pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2 + ) metastatic breast cancer (mBC) with brain metastases (BMs) from DESTINY-Breast (DB)-01, -02, and-03 [J ] . Ann Oncol , 2023 , 34 : S335-S336.
HARBECK N , CIRUELOS E , JERUSALEM G , et al . Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial [J ] . Nat Med , 2024 , 30 ( 12 ): 3717 - 3727 .
ZHANG X J , YEUNG K T . Metastatic triple-negative breast cancer [J ] . Curr Breast Cancer Rep , 2023 , 15 ( 3 ): 288 - 297 .
CORTES J , RUGO H S , CESCON D W , et al . Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer [J ] . N Engl J Med , 2022 , 387 ( 3 ): 217 - 226 .
JIANG Z F , OUYANG Q C , SUN T , et al . Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial [J ] . Nat Med , 2024 , 30 ( 1 ): 249 - 256 . DOI: 10.1038/s41591-023-02677-x http://doi.org/10.1038/s41591-023-02677-x
GUARINI C , SANTORO A N , MELACCIO A , et al . Metronomic chemotherapy and breast cancer: a critical evaluation of its role in the new landscape of therapeutics [J ] . Expert Opin Drug Saf , 2025 , 24 ( 1 ): 9 - 16 .
MO H N , YU Y P , SUN X Y , et al . Metronomic chemotherapy plus anti-PD-1 in metastatic breast cancer: a Bayesian adaptive randomized phase 2 trial [J ] . Nat Med , 2024 , 30 ( 9 ): 2528 - 2539 . DOI: 10.1038/s41591-024-03088-2 http://doi.org/10.1038/s41591-024-03088-2
BARDIA A , RUGO H S , TOLANEY S M , et al . Final results from the randomized phase Ⅲ ASCENT clinical trial in metastatic triple-negative breast cancer and association of outcomes by human epidermal growth factor receptor 2 and trophoblast cell surface antigen 2 expression [J ] . J Clin Oncol , 2024 , 42 ( 15 ): 1738 - 1744 .
XU B H , MA F , WANG T , et al . A phase Ⅱb, single arm, multicenter trial of sacituzumab govitecan in Chinese patients with metastatic triple-negative breast cancer who received at least two prior treatments [J ] . Int J Cancer , 2023 , 152 ( 10 ): 2134 - 2144 .
XU B H , YIN Y M , FAN Y , et al . Sacituzumab tirumotecan (SKB264/MK-2870) in patients (pts) with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC): results from the phase Ⅲ OptiTROP-Breast01 study [J ] . J Clin Oncol , 2024 , 42 ( 16_suppl ): 104 .
BARDIA A , KROP I E , KOGAWA T , et al . Datopotamab deruxtecan in advanced or metastatic HR + /HER2 - and triple-negative breast cancer: results from the phase Ⅰ TROPION-PanTumor01 study [J ] . J Clin Oncol , 2024 , 42 ( 19 ): 2281 - 2294 .
WANG T . Datopotamab deruxtecan (Dato-DXd) in Chinese patients with heavily pretreated advanced or metastatic triple-negative breast cancer: results from the phase 1/2 TROPION-PanTumor02 study [C ] . CSCO , 2024 .
0
Views
1805
下载量
0
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621