乳腺病理学新技术的进展和争议

张钰佳; 马力

doi:10.19401/j.cnki.1007-3639.2025.03.004

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乳腺病理学新技术的进展和争议

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- 乳腺病理学新技术的进展和争议
- Advances and controversies in new techniques of breast pathology
- 中国癌症杂志 2025年35卷第3期页码：283-290
- 作者机构：
  
  河北医科大学第四医院乳腺中心，河北石家庄 050011
- 作者简介：
  
  [ "张钰佳（ORCID: 0009-0007-1866-0364），硕士。" ]
  [ "马力，主任医师，教授，博士研究生导师，河北医科大学第四医院乳腺中心病区主任。中国抗癌协会乳腺癌专业委员会委员，中国临床肿瘤学会（CSCO）乳腺癌专家委员会委员，中国医师协会外科医师分会乳腺外科专家工作组委员，中华医学会肿瘤学分会乳腺肿瘤学组委员，中国医药教育协会乳腺疾病专业委员会常委，河北省医师学会外科医师分会乳腺学组组长，河北省肿瘤防治联合会乳腺癌专业委员会主任委员，河北省临床肿瘤学会乳腺癌专家委员会候任主任委员。" ]
- 基金信息：
  
  河北医科大学第四医院科研创新团队支持计划(2023B01)
- DOI：10.19401/j.cnki.1007-3639.2025.03.004
  中图分类号： R737.9
- 收稿：2025-02-18，
  
  修回：2025-03-12，
  
  纸质出版：2025-03-30
- 稿件说明：
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张钰佳, 马力. 乳腺病理学新技术的进展和争议[J]. 中国癌症杂志, 2025,35(3):283-290.

Yujia ZHANG, Li MA. Advances and controversies in new techniques of breast pathology[J]. China Oncology, 2025, 35(3): 283-290.
张钰佳, 马力. 乳腺病理学新技术的进展和争议[J]. 中国癌症杂志, 2025,35(3):283-290. DOI： 10.19401/j.cnki.1007-3639.2025.03.004.

Yujia ZHANG, Li MA. Advances and controversies in new techniques of breast pathology[J]. China Oncology, 2025, 35(3): 283-290. DOI： 10.19401/j.cnki.1007-3639.2025.03.004.

摘要

乳腺病理学技术的发展为乳腺癌的精准分型和个体化治疗提供了基础支撑。目前，乳腺癌诊疗精准化已成为基本趋势，多种新型药物的出现对乳腺癌病理学诊断的精确度提出了更高的要求。德曲妥珠单抗（trastuzumab deruxtecan，T-DXd）的应用为人表

皮生长因子受体2（human epidermal growth factor receptor 2，HER2）低表达（HER2-low）与HER2超低表达（HER2-ultra low）乳腺癌患者提供了新的治疗可能。随着HER2表达状态分类的细化，免疫组织化学（immunohistochemistry，IHC）技术作为传统HER2检测手段的检验效能受到挑战，HER2-low存在判读一致性较差的问题，判读结果存在空间异质性、时间异质性并受空白切片保存时间影响，寻找可提高IHC检验效能和判读准确度的辅助方法以及合理可及的新型HER2检测方式是当前重要的探索方向。在此背景下，HER2-low由于不具有明显稳定的生物学和病理学特征，以及缺乏特殊的治疗获益和预后相关性，目前尚不适宜被视作独立的分子分型。随着基因检测技术的普及和发展，多种乳腺癌致病相关基因被确定，相应药物的研发应用使基因诊断在乳腺癌诊疗中的决策权重提升。近年来磷脂酰肌醇3-激酶（phosphoinositide 3-kinase，PI3K）/蛋白激酶B（protein kinase B，AKT）/哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）信号通路（简称PAM通路）抑制剂在激素受体（hormone receptor，HR）阳性/HER2阴性晚期乳腺癌治疗中显示出良好潜力，临床对于

PIK3CA/AKT1/PTEN

基因检测的重视程度不断提升，初检时间前移成为趋势；检测样本首选肿瘤组织样本，可使用血浆样本作为必要补充，原发肿瘤或复发肿瘤样本检测效力相似，均可酌情选择。

BRCA

突变是乳腺癌常见的基因突变类型之一，目前国内外多部指南对于

BRCA

突变检测的目标人群推荐情况存在细节差异，但总体原则均为根据患者确诊年龄、相关家族史及既往治疗反应选择

BRCA

突变风险较高和可能从多腺苷二磷酸核糖聚合酶[poly (ADP-ribose) polymerase，PARP

]

抑制剂治疗中获益的患者。本文汇总国内外乳腺病理学技术的最新进展和存在的争议，着重介绍HER2-low与HER2-ultra low乳腺癌的诊断标准及当前检测存在的不足、PAM通路异常乳腺癌的诊疗进展以及

BRCA

基因突变的检测目标人群选择，拟为乳腺癌临床诊疗提供参考并从临床医师角度探讨乳腺病理学的发展方向。

Abstract

The development of breast pathology technology provides basic support for precise typing and individualized treatment of breast cancer. Precision in breast cancer diagnosis and management is evolving as a fundamental trend

with the advent of novel therapeutic agents necessitating enhanced accuracy in pathological diagnostic evaluations. The application of trastuzumab deruxtecan (T-DXd) has offered new therapies for breast cancer patients with human epidermal growth factor receptor 2 (HER2)-low and HER2-ultra low status. With the refinement of the classification for HER2 expression status

as a traditional detection method

the efficacy of immunohistochemistry (IHC) has been challenged. In addition

HER2-low has poor interpretation consistency

with spatial and temporal heterogeneity

which is affected by the storage time of the blank slides. Nowadays

finding auxilia

ry methods that can effectively improve the testing efficiency and interpretation accuracy of IHC as well as new accessible HER2 detection methods are important exploration directions. Whether HER2-low can be considered an independent molecular type of breast cancer has become an important issue with the update of treatments and the progress of new drugs. However

the answer is no at this time due to the absence of distinct and stable biological and pathological features and the lack of specific therapeutic benefit and prognostic relevance. With the widespread adoption and advancement of genomic profiling technologies

multiple causative genetic mutations associated with breast cancer have been identified. The development and clinical application of targeted drugs have elevated genomic profiling to an increasingly pivotal role in clinical decision-making for breast cancer treatment. In recent years

multiple inhibitors targeting the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway (PAM pathway) have demonstrated promising therapeutic efficacy in hormone receptor (HR) positive/HER2-negative breast cancer. The clinical prioritization of

PIK3CA/AKT1/PTEN

molecular profiling has been intensified

and the trend is to move forward the time of the initial test. Tumor tissue samples are preferred for testing

and plasma samples can be used as a necessary supplement. Samples from primary or recurrent tumors are considered to have similar testing efficacy and can be selected as appropriate.

BRCA

mutation is one of the common types of genetic mutations in breast cancer. While current guidelines vary in specifics regarding target populations

they universally prioritize clinical parameters including diagnostic age

family history

and treatment response to identify patients who have elevated

BRCA

mutation risks and may benefit from poly (ADP-ribose) polymerase (PARP) inhibitor therapy. This article summarized the

latest advances and controversies in breast pathology techniques

focusing on the diagnostic criteria and methodological limitations in detecting HER2-low and HER2-ultra low breast cancers

therapeutic progress in PAM pathway-aberrant breast cancer

and the target population for detecting

BRCA

gene mutations.

关键词

Keywords

references

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