外科理论与实践

外科理论与实践 >

2026 , Vol. 31 >Issue 03: 227 - 233

DOI: https://doi.org/10.16139/j.1007-9610.2026.03.08

讲座

CDK4/6抑制剂在早期乳腺癌辅助治疗应用的热点问题

  • 徐佳妍 ,
  • 朱思吉
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  • 上海交通大学医学院附属瑞金医院普外科 乳腺疾病诊治中心， 上海 200025
作者贡献/Authors’ contributions

徐佳妍负责资料收集和撰写；朱思吉负责撰写、审查和修订。所有作者均阅读并确认最终稿。

朱思吉，E-mail: zsj_mu@yeah.net

收稿日期: 2025-05-11

  网络出版日期: 2026-08-11

基金资助

国家自然科学基金(82573726)

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Topical topics of CDK4/6 inhibitors in adjuvant treatment of early breast cancer

  • XU Jiayan ,
  • ZHU Siji
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  • Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Received date: 2025-05-11

  Online published: 2026-08-11

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摘要

激素受体阳性/人表皮生长因子受体2阴性（HR+/HER2-）乳腺癌是乳腺癌最主要的分子亚型。该亚型病人即便完成标准辅助内分泌治疗，仍面临持续存在的远期复发风险。细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂通过精准靶向阻断细胞周期异常增殖通路，在早期乳腺癌辅助治疗中可显著降低高危病人的复发风险，改写了HR+/HER2-早期乳腺癌的治疗格局。本文系统梳理了CDK4/6抑制剂辅助治疗早期乳腺癌的核心循证医学证据，深入解析当前临床实践中的热点争议问题，总结国内外权威指南推荐要点与个体化决策优化策略，并对未来研究方向进行展望，为临床规范化、精准化应用CDK4/6抑制剂提供参考。

关键词： CDK4/6抑制剂; HR+/HER2-乳腺癌; 早期乳腺癌; 辅助治疗; 复发风险

本文引用格式

徐佳妍 , 朱思吉 . CDK4/6抑制剂在早期乳腺癌辅助治疗应用的热点问题[J]. 外科理论与实践, 2026 , 31(03) : 227 -233 . DOI: 10.16139/j.1007-9610.2026.03.08

Abstract

Hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer is the predominant molecular subtype. However, even after completion of standard adjuvant endocrine therapy, patients of this subtype continue to face a persistent risk of late recurrence. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors precisely target dysregulated cell-cycle progression. They have been proved to significantly reduce the risk of recurrence in high-risk early-stage patients in the adjuvant setting, thereby reshaping the treatment landscape of HR+/HER2- early breast cancer. This review systematically summarized the key evidence supporting adjuvant CDK4/6 inhibitor therapy, critically analyzed current controversies in clinical practice, outlined major recommendations from international and national guidelines, discussed strategies for individualized treatment optimization, and provided perspectives on future research directions. These insights may help inform the standardized and precise use of CDK4/6 inhibitors for patients of early breast cancer.

Key words： CDK4/6 inhibitors; HR+/HER2- breast cancer; Early breast cancer; Adjuvant therapy; Recurrence risk

参考文献

[1] Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3):229-263.
[2] Xia C, Li H, Wu C, et al. Cancer burden and control in China: landscape, trends and challenges[J]. Nat Rev Clin Oncol, 2026.
[3] Iqbal J, Ginsburg O, Rochon P A, et al. Differences in breast cancer stage at diagnosis and cancer-specific survival by race and ethnicity in the United States[J]. JAMA, 2015, 313(2):165-173.
[4] Pan H, Gray R, Braybrooke J, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years[J]. N Engl J Med, 2017, 377(19):1836-1846.
[5] 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.
[6] Lu Y S, Im S A, Colleoni M, et al. Updated overall survival of ribociclib plus endocrine therapy versus endocrine therapy alone in pre- and perimenopausal patients with HR+/HER2-advanced breast cancer in MONALEESA-7: a phase Ⅲ randomized clinical trial[J]. Clin Cancer Res, 2022, 28(5):851-859.
[7] Freedman R A, Caswell-Jin J L, Hassett M, et al. Optimal adjuvant chemotherapy and targeted therapy for early breast cancer-cyclin-dependent kinase 4 and 6 inhibitors: ASCO guideline rapid recommendation update[J]. J Clin Oncol, 2024, 42(18):2233-2235.
[8] 中国抗癌协会乳腺癌专业委员会, 中华医学会肿瘤学分会乳腺肿瘤学组. 中国抗癌协会乳腺癌诊治指南与规范(2026年版)[J]. 肿瘤影像学, 2026, 35(1):114-211.
  The Society of Breast Cancer China Anti-Cancer Association, Breast Oncology Group of the Oncology Branch of the Chinese Medical Association. Guidelines for breast cancer diagnosis and treatment by China Anti-cancer Association (2026 edition)[J]. Oncoradiology, 2026, 35(1):114-211.
[9] Johnston S, Martin M, O'Shaughnessy J, et al. Overall survival with abemaciclib in early breast cancer[J]. Ann Oncol, 2026, 37(2):155-165.
[10] Fasching P A, Stroyakovskiy D, Yardley D A, et al. Ribociclib plus endocrine therapy in hormone receptor-positive/ERBB2-negative early breast cancer: 4-year outcomes from the NATALEE randomized clinical trial[J]. JAMA Oncol, 2025, 11(11):1364-1372.
[11] Crown J, Stroyakovskii D, Yardley D A, et al. Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR-positive/HER2-negative early breast cancer: 5-year follow-up of NATALEE efficacy outcomes and updated overall survival[J]. ESMO Open, 2025, 10(11):105858.
[12] Shao Z M, Hao J H, Wang S, et al. Dalpiciclib (Dalp) plus endocrine therapy (ET) as adjuvant treatment for HR+/HER2- early breast cancer (BC): The randomized, phase 3, DAWNA-A trial[J]. J Clin Oncol, 2025, 43(16):515.
[13] Rastogi P, O'Shaughnessy J, Martin M, et al. Adjuvant abemaciclib plus endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, high-risk early breast cancer: results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes[J]. J Clin Oncol, 2024, 42(9):987-993.
[14] Onesti C E, Jerusalem G. CDK4/6 inhibitors in breast cancer: differences in toxicity profiles and impact on agent choice. A systematic review and meta-analysis[J]. Expert Rev Anticancer Ther, 2021, 21(3):283-298.
[15] Im S A, Lu Y S, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer[J]. N Engl J Med, 2019, 381(4):307-316.
[16] Caswell-Jin J L, Freedman R A, Hassett M J, et al. Optimal adjuvant chemotherapy and targeted therapy for early breast cancer-CDK4/6 inhibitors: ASCO rapid guideline update clinical insights[J]. JCO Oncol Pract, 2025, 21(3):287-291.
[17] Rugo H S, O'Shaughnessy J, Boyle F, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: safety and patient-reported outcomes from the monarchE study[J]. Ann Oncol, 2022, 33(6):616-627.
[18] Kalinsky K, Bianchini G, Hamilton E, et al. Abemaciclib plus fulvestrant in advanced breast cancer after progression on CDK4/6 inhibition: results from the phase Ⅲ postMONARCH trial[J]. J Clin Oncol, 2025, 43(9):1101-1112.
[19] Kalinsky K, Accordino M K, Chiuzan C, et al. Rando-mized phase Ⅱ trial of endocrine therapy with or without ribociclib after progression on cyclin-dependent kinase 4/6 inhibition in hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer: MAINTAIN trial[J]. J Clin Oncol, 2023, 41(24):4004-4013.
[20] 陈冬芍, 王树森. 精准靶向时代的激素受体阳性晚期乳腺癌治疗进展[J]. 肿瘤药学, 2026, 16(1):11-23.
  Chen Dongshao, Wang Shusen. Advances in the treatment of hormone receptor-positive advanced breast cancer in the era of precision targeted therapy[J]. Anti-tumor Pharm, 2026, 16(1):11-23.
[21] Goetz M P, Cicin I, Testa L, et al. Impact of dose reductions on adjuvant abemaciclib efficacy for patients with high-risk early breast cancer: analyses from the monarchE study[J]. NPJ Breast Cancer, 2024, 10(1):34.
[22] Slamon D J, Fasching P A, Hurvitz S, et al. Rationale and trial design of NATALEE: a phase Ⅲ trial of adjuvant ribociclib+endocrine therapy versus endocrine therapy alone in patients with HR+/HER2- early breast cancer[J]. Ther Adv Med Oncol, 2023, 15:17588359231178125.
[23] Burris H A, Chan A, Bardia A, et al. Safety and impact of dose reductions on efficacy in the randomised MONALEESA-2, -3 and -7 trials in hormone receptor-positive, HER2-negative advanced breast cancer[J]. Br J Cancer, 2021, 125(5):679-686.
[24] Hamilton E, Decker T, Rugo H S, et al. Impact of ribociclib dose reduction on efficacy in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) in NATALEE[J]. Clin Cancer Res, 2025, 31(12):P1-11-6.
[25] Mayer E L, Trapani D, Kim S E, et al. TRADE: a phase Ⅱ trial to assess the tolerability of abemaciclib dose escalation in early-stage HR-positive/HER2-negative breast cancer[J]. Ann Oncol, 2026, 37(1):117-124.
[26] Barrios C H, Harbeck N, Hortobagyi G N, et al. NATALEE update: safety and treatment (tx) duration of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2-early breast cancer (EBC)[J]. ESMO Open, 2024, 9(4):103101.
[27] Harbeck N, Gluz O, Christgen M, et al. ADAPTcycle: adjuvant dynamic marker-adjusted personalized therapy (ADAPT) comparing endocrine therapy plus ribociclib versus chemotherapy in intermediate-risk HR+/HER2-early breast cancer (EBC)[J]. J Clin Oncol, 2020,38:TPS601-TPS.
[28] Yardley D A, Untch M, Barrios C H, et al. Baseline (BL) characteristics and efficacy endpoints for patients (pts) with node-negative (N0) HR+/HER2- early breast cancer (EBC): NATALEE trial[J]. J Clin Oncol, 2024, 42(16):512.
[29] Sparano J A, Gray R J, Makower D F, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer[J]. N Engl J Med, 2018, 379(2):111-121.
[30] Piccart M, Van't Veer L J, Poncet C, et al. 70-gene signature as an aid for treatment decisions in early breast cancer: updated results of the phase 3 randomised MINDACT trial with an exploratory analysis by age[J]. Lancet Oncol, 2021, 22(4):476-488.
[31] 中华医学会外科学分会乳腺外科学组. 早期乳腺癌多基因检测临床实践指南(2026版)[J]. 中国实用外科杂志, 2026, 46(3):289-293.
  Chinese Society of Breast Surgery, Chinese Society of Surgery, Chinese Medical Association. Clinical practice guidelines for multigene assays in early breast cancer (2026 edition)[J]. Chin J Prac Surg, 2026, 46(3):289-293.
[32] Andre F, Ismaila N, Allison K H, et al. Biomarkers for adjuvant endocrine and chemotherapy in early-stage breast cancer: ASCO guideline update[J]. J Clin Oncol, 2022, 40(16):1816-1837.
[33] Goetz M P, Turner N, Sasano H, et al. 240MO Prognostic and predictive impact of estrogen/progesterone receptor (ER/PR), and Ki-67 expression: an exploratory analysis from the monarchE trial in patients with high-risk, HR+, HER2-, early breast cancer (EBC)[J]. Ann Oncol, 2023, 34:S278-S279.
[34] Higgins T, Kantor O, Harrison B, et al. Defining the bio-logy of estrogen receptor-low-positive breast cancer[J]. Ann Surg Oncol, 2024, 31(4):2244-2252.
[35] Prat A, Chaudhury A, Solovieff N, et al. Correlative biomarker analysis of intrinsic subtypes and efficacy across the MONALEESA phase Ⅲ studies[J]. J Clin Oncol, 2021, 39(13):1458-1467.
[36] Martin M, Hegg R, Kim S B, et al. Treatment with adjuvant abemaciclib plus endocrine therapy in patients with high-risk early breast cancer who received neoadjuvant chemotherapy: a prespecified analysis of the monarchE randomized clinical trial[J]. JAMA Oncol, 2022, 8(8):1190-1194.
[37] Tutt A N J, Garber J E, Kaufman B, et al. Adjuvant olaparib for patients with BRCA1-or BRCA2-mutated breast cancer[J]. N Engl J Med, 2021, 384(25):2394-2405.
[38] 龙葵英, 石英, 刘丹, 等. 奥拉帕利致不良反应文献分析[J]. 中国药业, 2025, 34(15):118-124.
  Long Kuiying, Shi Ying, Liu Dan, et al. Literature analysis of adverse drug reactions induced by olaparib[J]. China Pharm, 2025, 34(15):118-124.
[39] O'Keefe K, Desai N V, Tan A R. Practical guidance on abemaciclib in combination with adjuvant endocrine therapy for treating hormone receptor-positive, human epidermal growth factor receptor 2-negative high-risk early breast cancer[J]. Breast Cancer (Dove Med Press), 2024, 16:517-527.
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