聚力分型精准，引领诊疗变革——乳腺癌精准诊疗新模式

张思维; 马丁; 江一舟; 邵志敏

doi:10.19401/j.cnki.1007-3639.2024.11.007

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聚力分型精准，引领诊疗变革——乳腺癌精准诊疗新模式

综述 | 更新时间：2025-12-31

- 聚力分型精准，引领诊疗变革——乳腺癌精准诊疗新模式
- “Subtype-precise” therapy leads diagnostic and therapeutic innovations: a new pattern for precision treatment of breast cancer
- 中国癌症杂志 2024年34卷第11期页码：1045-1052
- 作者机构：
  
  复旦大学附属肿瘤医院乳腺外科，复旦大学乳腺癌研究所，复旦大学上海医学院肿瘤学系，上海 200032
- 作者简介：
  
  [ "张思维（ORCID: 0000-0001-8872-3809），博士在读。" ]
  邵志敏（ORCID: 0000-0002-4503-148X），主任医师、教授，复旦大学肿瘤研究所所长、复旦大学乳腺癌研究所所长、复旦大学附属肿瘤医院大外科主任兼乳腺外科主任。
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2024.11.007
  中图分类号： R737.9
- 收稿：2024-09-04，
  
  修回：2024-11-13，
  
  纸质出版：2024-11-30
- 稿件说明：
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张思维, 马丁, 江一舟, 等. 聚力分型精准，引领诊疗变革——乳腺癌精准诊疗新模式[J]. 中国癌症杂志, 2024,34(11):1045-1052.

Siwei ZHANG, Ding MA, Yizhou JIANG, et al. “Subtype-precise” therapy leads diagnostic and therapeutic innovations: a new pattern for precision treatment of breast cancer[J]. China Oncology, 2024, 34(11): 1045-1052.
张思维, 马丁, 江一舟, 等. 聚力分型精准，引领诊疗变革——乳腺癌精准诊疗新模式[J]. 中国癌症杂志, 2024,34(11):1045-1052. DOI： 10.19401/j.cnki.1007-3639.2024.11.007.

Siwei ZHANG, Ding MA, Yizhou JIANG, et al. “Subtype-precise” therapy leads diagnostic and therapeutic innovations: a new pattern for precision treatment of breast cancer[J]. China Oncology, 2024, 34(11): 1045-1052. DOI： 10.19401/j.cnki.1007-3639.2024.11.007.

摘要

乳腺癌是全球女性中发病率最高的恶性肿瘤，发病率逐年上升。乳腺癌的治疗经历了数次变革，从最初单一的外科手术，发展至全身治疗，进而至近年的分型治疗。临床上，乳腺癌根据激素受体（hormone receptor，HR）和人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）的表达被细分为腔面型、HER2阳性型和三阴性乳腺癌（triple-negative breast cancer，TNBC），并分别采取内分泌治疗、抗HER2靶向治疗和化疗。然而，分型治疗策略不够个体化，仍有约30%的患者面临治疗耐药和复发转移。HER2阳性乳腺癌患者的总生存率不断提高，而TNBC和腔面型晚期乳腺癌患者的生存改善不显著。为克服“分类不够彻底，治疗不够精准”的临床瓶颈，“分型精准”治疗应运而生。“分型精准”治疗是指在现有分型基础上进一步亚分型，并找到特定靶点开展精准治疗，具有“人群广覆盖，治疗高特异”的特点。复旦大学附属肿瘤医院乳腺癌多学科团队历时10年，建立中国乳腺癌多组学图谱（Chinese Breast Cancer Genome Atlas，CBCGA），并深入解析TNBC的分子生物学特征，建立了与临床疗效密切相关的TNBC“复旦分型”：腔面雄激素受体型（luminal androgen receptor subtype，LAR），可用抗HER2和细胞周期蛋白依赖性激酶CDK4/6抑制剂靶向治疗；免疫调节型（immunomodulatory subtype，IM），适合免疫治疗；基底样免疫抑制型（basal-like immune-suppressed subtype，BLIS），可使用铂类或多腺苷二磷酸核糖聚合酶[poly (ADP-ribose) polymerase，PARP]抑制剂等DNA损伤药物；间充质型（mesenchymal-like subtype，MES），可使用抗肿瘤干细胞、抗血管生成治疗。项目组后续将“分型精准”模式推广至人数最多、占比最高、复发风险可持续数十年的乳腺癌亚型—腔面型乳腺癌中，将腔面型乳腺癌分为4个分子亚型并提出相应精准治疗策略：经典腔面型（SNF1），对内分泌治疗敏感；免疫型（SNF2），可开展免疫治疗；增殖型（SNF3），可通过阻滞细胞周期治疗；受体酪氨酸激酶驱动型（SNF4），可靶向受体酪氨酸激酶治疗。团队正在开展Ⅲ期随机对照临床试验，以进一步验证“分型精准”治疗策略，并推广“分型精准”复旦经验，带动整体乳腺癌疗效提升。展望未来，借助人工智能等新兴诊断工具，以及各个亚型靶向标志物和靶向药物的更新迭代，乳腺癌“分型精准”治疗有望进一步优化和推广，改善患者预后，引领乳腺癌治疗方式的新变革。

Abstract

Breast cancer is the most common malignant tumor among women worldwide

with incidence rates rising annually. The treatment of breast cancer has undergone significant transformations

evolving from an initial reliance on a single surgical approach to the incorporation of systemic therapy

and more recently

to subtype-specific therapy. Clinically

breast cancer is classified into luminal

HER2-positive

and triple-negative breast cancer (TNBC) based on the expression of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)

with corresponding treatments including endocrine therapy

anti-HER2 targeted therapy

and chemotherapy. However

the current subtype-based treatment strategies lack personalization

with approximately 30% of patients still facing resistance and relapse. While the overall survival rate of patients with HER2-positive breast cancer has been steadily increasing

significant survival improvements have not been observed in patients with triple-negative and luminal breast cancer. To overcome the clinical bottleneck of “incomplete classification and imprecise treatment”

the concept of “subtype-precise” therapy has emerged. This innovative approach involves further subclassification of existing subtypes to identify specific targets for precision treatment

characterized by broad population coverage and high specificity. Over the past decade

the multidisciplinary team at Fudan University Shanghai Cancer Center has established a comprehensive molecular portrait of Chinese Breast Cancer Genome Atlas (CBCGA). They deeply analyzed the molecular characteristics of TNBC

leading to the development of a “Fudan subtype” closely related to clinical outcomes: luminal androgen receptor subtype (LAR)

which can be targeted with anti-HER2 and CDK4/6 inhibitors; the immunomodulatory subtype (IM)

suitable for immunotherapy; basal-like immune-suppressed subtype (BLIS)

which can be treated with platinum-based drugs or poly (ADP-ribose) polymerase (PARP) inhibitors; and mesenchymal-like subtype (MES)

which can be treated with anti-cancer stem cell and anti-angiogenic therapies. The team then extended the concept of “subtype-precise” to luminal breast cancer

the subtype with the largest number

the highest proportion and the risk of recurrence for decades. They divided it into four molecular subtypes and proposing corresponding precision treatment strategies: canonical luminal subtype (SNF1)

sensitive to endocrine therapy; immunogenic subtype (SNF2)

amenable to immunotherapy; proliferative subtype (SNF3)

treatable by CDK4/6 inhibitors; and receptor tyrosine kinase-driven subtype (SNF4)

targetable with tyrosine kinase inhibitors. The team is currently conducting phase Ⅲ randomized controlled trials to further validate the “subtype-precise” therapy and promote the “subtype-precise” Fudan experience to enhance overall breast cancer treatment efficacy. Looking forward

the integration of emerging diagnostic tools

such as artificial intelligence

coupled with the continuous update of subtype-specific targets and targeted therapies

is expected to further refine and expand “subtype-precise” therapy. This approach holds great promises for enhancing patient prognosis and leading a new revolution in breast cancer treatment.

关键词

Keywords

references

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