乳腺癌分子分型与多学科综合诊疗进展及前沿展望
Advances and Frontier Perspectives in Molecular Subtyping and Multidisciplinary Comprehensive Treatment of Breast Cancer
摘要: 乳腺癌现已成为全球女性发病率首位的恶性肿瘤。其生物学异质性决定了单一的解剖学分期已无法满足现代临床诊疗的需求。近年来，随着分子生物学技术的突破与多学科协作(MDT)模式的深化，乳腺癌的临床路径发生了从“最大可耐受治疗”向“基于分子分型驱动的精准医疗”的范式转变。本文系统回顾了乳腺癌的流行病学特征与风险干预策略，详述了影像与病理联合诊断体系的演变。在局部干预层面，探讨了外科手术与放射治疗的“降阶梯”理念；在全身系统性治疗层面，重点剖析了涵盖CDK4/6抑制剂、新辅助治疗模式、PARP抑制剂以及新型抗体偶联药物(ADC)的最新循证医学进展。最后，本文对循环肿瘤DNA (ctDNA)微小残留病灶监测与人工智能辅助决策在临床转化的前景进行了探讨，为乳腺癌的全周期规范化管理提供了参考。
Abstract: Breast cancer is currently the most commonly diagnosed malignancy among women worldwide. Its inherent biological heterogeneity dictates that relying solely on anatomical staging can no longer satisfy the requirements of modern clinical practice. In recent years, breakthroughs in molecular biology technologies and the deepening integration of the multidisciplinary team (MDT) approach have driven a paradigm shift in the clinical pathways of breast cancer, transitioning from “maximum tolerated treatment” to “molecular subtype-driven precision medicine”. This article systematically reviews the epidemiological characteristics and risk intervention strategies for breast cancer, detailing the evolution of the integrated imaging and pathological diagnostic system. Regarding locoregional interventions, the article discusses the concept of “de-escalation” in surgery and radiotherapy. In the realm of systemic therapy, it highlights the latest evidence-based advances encompassing CDK4/6 inhibitors, neoadjuvant treatment modalities, PARP inhibitors, and novel antibody-drug conjugates (ADCs). Finally, this review explores the translational clinical prospects of circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) monitoring and artificial intelligence (AI)-assisted decision-making, aiming to provide a reference for the standardized whole-course management of breast cancer.
文章引用：阳芃, 龚建平. 乳腺癌分子分型与多学科综合诊疗进展及前沿展望[J]. 临床医学进展, 2026, 16(4): 2525-2533. https://doi.org/10.12677/acm.2026.1641503

参考文献

[1] Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. [Google Scholar] [CrossRef] [PubMed]
[2] 郑荣寿, 陈茹, 韩冰峰, 等. 2022年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2024, 46(3): 221-231.
[3] 赫捷, 陈万青, 李霓, 等. 中国女性乳腺癌筛查与早诊早治指南(2021, 北京) [J]. 中国肿瘤, 2021, 30(3): 161-191.
[4] Miki, Y., Swensen, J., Shattuck-Eidens, D., Futreal, P.A., Harshman, K., Tavtigian, S., et al. (1994) A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene brca1. Science, 266, 66-71. [Google Scholar] [CrossRef] [PubMed]
[5] Beral, V. (2003) Breast Cancer and Hormone-Replacement Therapy in the Million Women Study. The Lancet (London, England), 362, 419-427.
[6] Renehan, A.G., Tyson, M., Egger, M., Heller, R.F. and Zwahlen, M. (2008) Body-Mass Index and Incidence of Cancer: A Systematic Review and Meta-Analysis of Prospective Observational Studies. The Lancet, 371, 569-578. [Google Scholar] [CrossRef] [PubMed]
[7] 中国研究型医院学会乳腺专业委员会, 中国女性乳腺癌预防共识专家组. 中国女性乳腺癌预防专家共识[J]. 中国研究型医院, 2022, 9(4): 5-13.
[8] Tabár, L., Dean, P.B., Kaufman, C.S., Duffy, S.W. and Chen, H. (2000) A New Era in the Diagnosis of Breast Cancer. Surgical Oncology Clinics of North America, 9, 233-277. [Google Scholar] [CrossRef] [PubMed]
[9] Shen, S., Zhou, Y., Xu, Y., Zhang, B., Duan, X., Huang, R., et al. (2015) A Multi-Centre Randomised Trial Comparing Ultrasound vs Mammography for Screening Breast Cancer in High-Risk Chinese Women. British Journal of Cancer, 112, 998-1004. [Google Scholar] [CrossRef] [PubMed]
[10] 杨文涛, 步宏. 乳腺癌雌、孕激素受体免疫组织化学检测指南[J]. 中华病理学杂志, 2015(4): 237-239.
[11] 《乳腺癌her2检测指南(2024版)》编写组. 乳腺癌her2检测指南(2024版) [J]. 中华病理学杂志, 2024, 53(12): 1192-1202.
[12] Perou, C.M., Sørlie, T., Eisen, M.B., van de Rijn, M., Jeffrey, S.S., Rees, C.A., et al. (2000) Molecular Portraits of Human Breast Tumours. Nature, 406, 747-752. [Google Scholar] [CrossRef] [PubMed]
[13] 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, 邵志敏, 等. 中国抗癌协会乳腺癌诊治指南与规范(2026年版) [J]. 中国癌症杂志, 2025, 35(12): 1157-1255.
[14] Davies, C., Pan, H., Godwin, J., Gray, R., Arriagada, R., Raina, V., et al. (2013) Long-Term Effects of Continuing Adjuvant Tamoxifen to 10 Years versus Stopping at 5 Years after Diagnosis of Oestrogen Receptor-Positive Breast Cancer: ATLAS, a Randomised Trial. The Lancet, 381, 805-816. [Google Scholar] [CrossRef] [PubMed]
[15] Sparano, J.A., Gray, R.J., Makower, D.F., Pritchard, K.I., Albain, K.S., Hayes, D.F., et al. (2018) Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. New England Journal of Medicine, 379, 111-121. [Google Scholar] [CrossRef] [PubMed]
[16] Finn, R.S., Martin, M., Rugo, H.S., Jones, S., Im, S., Gelmon, K., et al. (2016) Palbociclib and Letrozole in Advanced Breast Cancer. New England Journal of Medicine, 375, 1925-1936. [Google Scholar] [CrossRef] [PubMed]
[17] Johnston, S.R.D., Harbeck, N., Hegg, R., Toi, M., Martin, M., Shao, Z.M., et al. (2020) Abemaciclib Combined with Endocrine Therapy for the Adjuvant Treatment of HR+, HER2−, Node-Positive, High-Risk, Early Breast Cancer (Monarche). Journal of Clinical Oncology, 38, 3987-3998. [Google Scholar] [CrossRef] [PubMed]
[18] Cortés, J., Kim, S., Chung, W., Im, S., Park, Y.H., Hegg, R., et al. (2022) Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. New England Journal of Medicine, 386, 1143-1154. [Google Scholar] [CrossRef] [PubMed]
[19] 《中国乳腺癌新辅助治疗专家共识(2022年版)》专家组. 中国乳腺癌新辅助治疗专家共识(2022年版) [J]. 中国癌症杂志, 2022, 32(1): 81-89.
[20] Baselga, J., Cortés, J., Kim, S., Im, S., Hegg, R., Im, Y., et al. (2012) Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer. New England Journal of Medicine, 366, 109-119. [Google Scholar] [CrossRef] [PubMed]
[21] von Minckwitz, G., Huang, C., Mano, M.S., Loibl, S., Mamounas, E.P., Untch, M., et al. (2019) Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. New England Journal of Medicine, 380, 617-628. [Google Scholar] [CrossRef] [PubMed]
[22] 中国医药教育协会乳腺癌个案管理师分会. 乳腺癌抗体偶联药物输注管理专家共识[J]. 中华医学杂志, 2023, 103(34): 2704-2712.
[23] 中国医药教育协会肿瘤药物临床研究专家委员会, 中国初级卫生保健基金会乳腺癌专业委员会. 三阴性乳腺癌免疫检查点抑制剂临床应用专家共识(2025版) [J]. 中华医学杂志, 2025, 105(38): 3394-3406.
[24] Jiang, Y.Z., Ma, D., Suo, C., et al. (2019) Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies. Cancer Cell, 35, 428-440.e5.
[25] Schmid, P., Cortes, J., Pusztai, L., McArthur, H., Kümmel, S., Bergh, J., et al. (2020) Pembrolizumab for Early Triple-Negative Breast Cancer. New England Journal of Medicine, 382, 810-821. [Google Scholar] [CrossRef] [PubMed]
[26] Cortes, J., Cescon, D.W., Rugo, H.S., Nowecki, Z., Im, S., Yusof, M.M., et al. (2020) Pembrolizumab plus Chemotherapy versus Placebo plus Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple-Negative Breast Cancer (KEYNOTE-355): A Randomised, Placebo-Controlled, Double-Blind, Phase 3 Clinical Trial. The Lancet, 396, 1817-1828. [Google Scholar] [CrossRef] [PubMed]
[27] Bardia, A., Hurvitz, S.A., Tolaney, S.M., Loirat, D., Punie, K., Oliveira, M., et al. (2021) Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. New England Journal of Medicine, 384, 1529-1541. [Google Scholar] [CrossRef] [PubMed]
[28] Tutt, A.N.J., Garber, J.E., Kaufman, B., Viale, G., Fumagalli, D., Rastogi, P., et al. (2021) Adjuvant Olaparib for Patients with brca1-or brca2-Mutated Breast Cancer. New England Journal of Medicine, 384, 2394-2405. [Google Scholar] [CrossRef] [PubMed]
[29] 刘荫华, 辛灵, 宋艺璇. 乳腺癌外科130余年发展回顾与中国临床实践[J]. 中华外科杂志, 2026, 64(1): 16-20.
[30] Fisher, B., Anderson, S., Bryant, J., Margolese, R.G., Deutsch, M., Fisher, E.R., et al. (2002) Twenty-Year Follow-Up of a Randomized Trial Comparing Total Mastectomy, Lumpectomy, and Lumpectomy Plus Irradiation for the Treatment of Invasive Breast Cancer. New England Journal of Medicine, 347, 1233-1241. [Google Scholar] [CrossRef] [PubMed]
[31] Giuliano, A.E., Ballman, K.V., McCall, L., Beitsch, P.D., Brennan, M.B., Kelemen, P.R., et al. (2017) Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival among Women with Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA, 318, 918-926. [Google Scholar] [CrossRef] [PubMed]
[32] Darby, S., McGale, P., Correa, C., et al. (2011) Effect of Radiotherapy after Breast-Conserving Surgery on 10-Year Recurrence and 15-Year Breast Cancer Death: Meta-Analysis of Individual Patient Data for 10,801 Women in 17 Randomised Trials. The Lancet (London, England), 378, 1707-1716.
[33] 张羽, 刘强. 液体活检在乳腺癌精准治疗中的应用进展及展望[J]. 中国癌症杂志, 2022, 32(8): 688-697.
[34] McKinney, S.M., Sieniek, M., Godbole, V., Godwin, J., Antropova, N., Ashrafian, H., et al. (2020) International Evaluation of an AI System for Breast Cancer Screening. Nature, 577, 89-94. [Google Scholar] [CrossRef] [PubMed]

为你推荐