HER2低表达乳腺癌新辅助化疗效果及其预后特征：一项单中心回顾性研究

王若曦; 吉芃; 龚悦; 陈盛

doi:10.19401/j.cnki.1007-3639.2023.07.006

您当前的位置：

首页 >

文章列表页 >

HER2低表达乳腺癌新辅助化疗效果及其预后特征：一项单中心回顾性研究

论著 | 更新时间：2025-12-31

- HER2低表达乳腺癌新辅助化疗效果及其预后特征：一项单中心回顾性研究
- Response rate and clinical outcome of HER2-low breast cancer after neoadjuvant therapy: a single-center retrospective study
- 中国癌症杂志 2023年33卷第7期页码：686-692
- 作者机构：
  
  复旦大学附属肿瘤医院乳腺外科，复旦大学上海医学院肿瘤学系，上海 200032
- 作者简介：
  
  [ "王若曦（ORCID: 0009-0000-9474-3240），博士，主治医师。" ]
  陈盛（ORCID: 0000-0003-3530-1287），博士，副主任医师。
- 基金信息：
  
  国家自然科学基金(82203097)
- DOI：10.19401/j.cnki.1007-3639.2023.07.006
  中图分类号： R737.9
- 收稿：2023-03-29，
  
  修回：2023-05-30，
  
  纸质出版：2023-07-30
- 稿件说明：
移动端阅览
王若曦, 吉芃, 龚悦, 等. HER2低表达乳腺癌新辅助化疗效果及其预后特征：一项单中心回顾性研究[J]. 中国癌症杂志, 2023,33(7):686-692.

Ruoxi WANG, Peng JI, Yue GONG, et al. Response rate and clinical outcome of HER2-low breast cancer after neoadjuvant therapy: a single-center retrospective study[J]. China Oncology, 2023, 33(7): 686-692.
王若曦, 吉芃, 龚悦, 等. HER2低表达乳腺癌新辅助化疗效果及其预后特征：一项单中心回顾性研究[J]. 中国癌症杂志, 2023,33(7):686-692. DOI： 10.19401/j.cnki.1007-3639.2023.07.006.

Ruoxi WANG, Peng JI, Yue GONG, et al. Response rate and clinical outcome of HER2-low breast cancer after neoadjuvant therapy: a single-center retrospective study[J]. China Oncology, 2023, 33(7): 686-692. DOI： 10.19401/j.cnki.1007-3639.2023.07.006.

摘要

背景与目的：

人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）是影响乳腺癌患者预后的主要标志物之一，也是乳腺癌病理学分型最主要的参考因素。本研究旨在探讨HER2低表达（HER2-low）乳腺癌患者的临床病理学特征，以及其在新辅助化疗中与疗效及预后的相关性。

方法：

回顾性纳入2009—2018年于复旦大学附属肿瘤医院接受新辅助化疗的HER2阴性乳腺癌患者的临床病理学相关信息，并将患者区分为HER2-low及无表达（HER2-0）组，分析其特征差异，采用单因素和多因素分析评估新辅助化疗后达病理学完全缓解（pathological complete response，pCR）的独立影响因素，采用Kaplan-Meier曲线评估不同HER2表达组的预后差异。

结果：

入组的772例患者中激素受体（hormonal receptor，HR）阳性患者的HER2-low比例显著高于H

R阴性患者。Logistic回归模型多因素分析结果显示，肿瘤大小（

0.001）、HR（

= 0.026）及HER2表达（

= 0.018）是pCR的独立预测因素。亚组分析提示，在三阴性乳腺癌（triple-negative breast cancer，TNBC）中，HER2-0与HER2-low的pCR率差异无统计学意义（

= 0.598）；而在Luminal型乳腺癌中，HER2-low患者pCR率为9.4%，显著低于HER2-0的19.3%（

= 0.003）。在非pCR（non-pCR）患者的生存分析中，HER2-low患者的预后显著优于HER2-0患者（

0.001），其5年生存率达72.2%，而HER2-0仅为56.0%。

结论：

HER2蛋白表达不同的HER2阴性患者具有不同的临床病理学特征，并与患者的化疗敏感性及预后有关。

Abstract

Background and purpose:

Human epidermal growth factor receptor 2 (HER2) is one of the main markers affecting the prognosis of breast cancer patients and the most important reference factor for the pathological classification of breast cancer. This study aimed to investigate the clinicopathological features of breast cancer with low expression of HER2 and its correlation with therapeutic effect and prognosis in neoadjuvant chemotherapy.

Methods:

The patients with HER2-negative breast cancer who received neoadjuvant chemotherapy in Fudan University Shanghai Cancer Center from 2009 to 2018 were retrospectively included. Clinicopathological information was collected

and the patients were divided into groups with low expression of HER2 (HER2-low) and no expression of HER2 (HER2-0)

and their characteristic differences were analyzed. The independent influencing factors of pathological complete response (pCR) after neoadjuvant chemotherapy were evaluated by univariate and multifactorial methods

and the prognostic differences among different HER2 expression groups were evaluated by Kaplan-Meier curve.

Results:

In the 772 patients enrolled in this study

the proportion of HER2-low was significantly higher in hormonal receptor (HR) positive patients than in HR negative patients. Multivariate analysis of logistic regression model showed that tumor size (

0.001)

HR (

0.026) and HER2 expression (

= 0.018) were independent predictors of pCR. Subgroup analysis indicated that there was no significant difference in pCR rates between HER2-0 and HER2-low triple-negative breast cancer (TNBC) (

= 0.598). In Luminal breast cancer

the pCR rate of HER2-low patients was 9.4%

which was significantly lower compared with HER2-0 patients (19.3%

= 0.003). In the survival analysis of non-pCR patients

the prognosis of HER2-low patients was significantly better compared with HER2-0 patients (

0.001)

and the 5-year survival rate was 72.2%

while the 5-year survival rate of HER2-0 patients was only 56.0%.

Conclusion:

HER2-negative patients with different expressions of HER2 protein have different clinicopathological characteristics

which are related to the chemotherapy sensitivity and prognosis of patients.

关键词

Keywords

references

CHOONG G M , CULLEN G D , O'SULLIVAN C C . Evolving standards of care and new challenges in the management of HER2-positive breast cancer [J ] . CA Cancer J Clin , 2020 , 70 ( 5 ): 355 - 374 . DOI: 10.3322/caac.v70.5 http://doi.org/10.3322/caac.v70.5 https://onlinelibrary.wiley.com/toc/15424863/70/5 https://onlinelibrary.wiley.com/toc/15424863/70/5

WOLFF A C , HAMMOND M E H , ALLISON K H , et al . Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update [J ] . J Clin Oncol , 2018 , 36 ( 20 ): 2105 - 2122 . DOI: 10.1200/JCO.2018.77.8738 http://doi.org/10.1200/JCO.2018.77.8738

KROP I E , LORUSSO P , MILLER K D , et al . A phase Ⅱ study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine [J ] . J Clin Oncol , 2012 , 30 ( 26 ): 3234 - 3241 . DOI: 10.1200/JCO.2011.40.5902 http://doi.org/10.1200/JCO.2011.40.5902 https://ascopubs.org/doi/10.1200/JCO.2011.40.5902 https://ascopubs.org/doi/10.1200/JCO.2011.40.5902

BASELGA J , LEWIS PHILLIPS G D , VERMA S , et al . Relationship between tumor biomarkers and efficacy in EMILIA, a phase Ⅲ study of trastuzumab emtansine in HER2-positive metastatic breast cancer [J ] . Clin Cancer Res , 2016 , 22 ( 15 ): 3755 - 3763 . DOI: 10.1158/1078-0432.CCR-15-2499 http://doi.org/10.1158/1078-0432.CCR-15-2499 https://aacrjournals.org/clincancerres/article/22/15/3755/79308/Relationship-between-Tumor-Biomarkers-and-Efficacy https://aacrjournals.org/clincancerres/article/22/15/3755/79308/Relationship-between-Tumor-Biomarkers-and-Efficacy

KIM S B , WILDIERS H , KROP I E , et al . Relationship between tumor biomarkers and efficacy in TH3RESA, a phase Ⅲ study of trastuzumab emtansine (T-DM1) vs treatment of physician’s choice in previously treated HER2-positive advanced breast cancer [J ] . Int J Cancer , 2016 , 139 ( 10 ): 2336 - 2342 . DOI: 10.1002/ijc.v139.10 http://doi.org/10.1002/ijc.v139.10 https://onlinelibrary.wiley.com/toc/10970215/139/10 https://onlinelibrary.wiley.com/toc/10970215/139/10

LEE C K , DAVIES L , GEBSKI V J , et al . Serum human epidermal growth factor 2 extracellular domain as a predictive biomarker for lapatinib treatment efficacy in patients with advanced breast cancer [J ] . J Clin Oncol , 2016 , 34 ( 9 ): 936 - 944 . DOI: 10.1200/JCO.2015.62.4767 http://doi.org/10.1200/JCO.2015.62.4767

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 . DOI: 10.1056/NEJMoa2203690 http://doi.org/10.1056/NEJMoa2203690 http://www.nejm.org/doi/10.1056/NEJMoa2203690 http://www.nejm.org/doi/10.1056/NEJMoa2203690

HORTOBAGYI G N . Comprehensive management of locally advanced breast cancer [J ] . Cancer , 1990 , 66 ( 6 Suppl ): 1387 - 1391 . DOI: 10.1002/1097-0142(19900915)66:14+<1387::aid-cncr2820661414>3.0.co;2-i http://doi.org/10.1002/1097-0142(19900915)66:14+<1387::aid-cncr2820661414>3.0.co;2-i

SCHWARTZ G F , HORTOBAGYI G N . Proceedings of the consensus conference on neoadjuvant chemotherapy in carcinoma of the breast, April 26-28, 2003, Philadelphia, Pennsylvania [J ] . Cancer , 2004 , 100 ( 12 ): 2512 - 2532 . DOI: 10.1002/cncr.20298 http://doi.org/10.1002/cncr.20298

Expert group of expert consensus on neoadjuvant treatment of breast cancer in China edition . Expert consensus on neoadjuvant treatment of breast cancer in China (2021 edition) [J ] . China Oncol , 2022 , 32 ( 1 ): 80 - 89 .

《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 ): 80 - 89 . DOI: 10.19401/j.cnki.1007-3639.2022.01.011 http://doi.org/10.19401/j.cnki.1007-3639.2022.01.011

Expert group of expert consensus on neoadjuvant treatment of breast cancer in China (2022 edition) . Expert consensus on neoadjuvant treatment of breast cancer in China (2022 edition) [J ] . China Oncol , 2022 , 32 ( 1 ): 80 - 89 .

MODI S N , SAURA C , YAMASHITA T , et al . Trastuzumab deruxtecan in previously treated HER2-positive breast cancer [J ] . N Engl J Med , 2020 , 382 ( 7 ): 610 - 621 . DOI: 10.1056/NEJMoa1914510 http://doi.org/10.1056/NEJMoa1914510 http://www.nejm.org/doi/10.1056/NEJMoa1914510 http://www.nejm.org/doi/10.1056/NEJMoa1914510

TAKEGAWA N , TSURUTANI J , KAWAKAMI H , et al . Fam-] trastuzumab deruxtecan, antitumor activity is dependent on HER2 expression level rather than on HER2 amplification [J ] . Int J Cancer , 2019 , 145 ( 12 ): 3414 - 3424 . DOI: 10.1002/ijc.v145.12 http://doi.org/10.1002/ijc.v145.12 https://onlinelibrary.wiley.com/toc/10970215/145/12 https://onlinelibrary.wiley.com/toc/10970215/145/12

PRAT A , BARDIA A , CURIGLIANO G , et al . An overview of clinical development of agents for metastatic or advanced breast cancer without ERBB 2 amplification (HER2-low) [J ] . JAMA Oncol , 2022 . [Online ahead of print ] .

DENKERT C , SEITHER F , SCHNEEWEISS A , et al . Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials [J ] . Lancet Oncol , 2021 , 22 ( 8 ): 1151 - 1161 . DOI: 10.1016/S1470-2045(21)00301-6 http://doi.org/10.1016/S1470-2045(21)00301-6

易巧 , 左怀全 . HER2低表达乳腺癌的临床病理学特征及其新辅助化疗疗效的相关影响因素分析 [J ] . 中国普外基础与临床杂志 , 2022 , 29 ( 9 ): 1213 - 1219 .

YI Q , ZUO H Q . Clinicopathological features of breast cancer with low HER2 expression and analysis of factors related to the efficacy of neoadjuvant chemotherapy [J ] . Chin J Bases Clin Gen Surg , 2022 , 29 ( 9 ): 1213 - 1219 .

SCHETTINI F , CHIC N , BRASÓ-MARISTANY F , et al . Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer [J ] . NPJ Breast Cancer , 2021 , 7 ( 1 ): 1 . DOI: 10.1038/s41523-020-00208-2 http://doi.org/10.1038/s41523-020-00208-2

HU X E , YANG P , CHEN S H , et al . Clinical and biological heterogeneities in triple-negative breast cancer reveals a non-negligible role of HER2-low [J ] . Breast Cancer Res , 2023 , 25 ( 1 ): 34 . DOI: 10.1186/s13058-023-01639-y http://doi.org/10.1186/s13058-023-01639-y

MODI S , PARK H , MURTHY R K , et al . Antitumor activity and safety of trastuzumab deruxtecan in patients with HER2-low-expressing advanced breast cancer: results from a phase Ⅰb study [J ] . J Clin Oncol , 2020 , 38 ( 17 ): 1887 - 1896 . DOI: 10.1200/JCO.19.02318 http://doi.org/10.1200/JCO.19.02318 https://ascopubs.org/doi/10.1200/JCO.19.02318 https://ascopubs.org/doi/10.1200/JCO.19.02318

FERNANDEZ A I , LIU M , BELLIZZI A , et al . Examination of low ERBB2 protein expression in breast cancer tissue [J ] . JAMA Oncol , 2022 , 8 ( 4 ): 1 - 4 . DOI: 10.1001/jamaoncol.2021.7239 http://doi.org/10.1001/jamaoncol.2021.7239

TARANTINO P , HAMILTON E , TOLANEY S M , et al . HER2-low breast cancer: pathological and clinical landscape [J ] . J Clin Oncol , 2020 , 38 ( 17 ): 1951 - 1962 . DOI: 10.1200/JCO.19.02488 http://doi.org/10.1200/JCO.19.02488

浏览量

2628

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

乳腺癌内乳前哨淋巴结活检与患者预后的相关性研究

Circ-0007766作为miR-1972海绵调控HER2表达促进乳腺癌细胞迁移和侵袭

乳腺癌原发灶与肝转移灶受体表达差异研究

乳腺癌内乳前哨淋巴结活检评估预后及指导个体化内乳照射：一项长期随访研究

2022年中国乳腺癌重要临床试验成果及最新进展