[1]程晓成,卫翀羿,隆建萍,等.人类表皮生长因子受体-2低表达型乳腺癌的临床分子特征及药物治疗研究进展[J].新乡医学院学报,2023,40(6):574-578.[doi:10.7683/xxyxyxb.2023.06.014]
　CHENG Xiaocheng,WEI Chongyi,LONG Jianping,et al.Research progress on clinical molecular characteristics and drug therapy of breast cancer with low expression of human epidermal growth factor receptor-2[J].Journal of Xinxiang Medical University,2023,40(6):574-578.[doi:10.7683/xxyxyxb.2023.06.014]
点击复制

人类表皮生长因子受体-2低表达型乳腺癌的临床分子特征及药物治疗研究进展
分享到：

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
40卷
期数:
2023年6
页码:
574-578
栏目:
综述
出版日期:
2023-06-05

文章信息/Info

Title:
Research progress on clinical molecular characteristics and drug therapy of breast cancer with low expression of human epidermal growth factor receptor-2
作者:
程晓成; 卫翀羿; 隆建萍; 马秀芬; 毛红岩; 独晓燕; 曹廷宝
（甘肃省妇幼保健院/甘肃省中心医院乳腺与甲状腺外科,甘肃　兰州　730000）
Author(s):
CHENG Xiaocheng; WEI Chongyi; LONG Jianping; MA Xiufen; MAO Hongyan; DU Xiaoyan; CAO Tingbao
（Department of Breast and Thyroid Surgery,Gansu Provincial Maternity and Child Health Hospital/Gansu Province Central Hospital,Lanzhou 730000,Gansu Province，China）
关键词:
人类表皮生长因子受体-2; 乳腺癌; 药物治疗
Keywords:
human epidermal growth factor receptor-2; breast cancer; drug therapy
分类号:
R730
DOI:
10.7683/xxyxyxb.2023.06.014
文献标志码:
A
摘要:
乳腺癌作为女性常见的恶性肿瘤之一，其发病率一直居高不下。目前，乳腺癌被划分为luminal A型、luminal B型、人类表皮生长因子受体-2(HER-2)过表达型和三阴型4种分子亚型。2021年版《乳腺癌诊疗指南》提出了HER-2低表达这一概念。尽管HER-2低表达有了明确的定义，并且HER-2低表达型乳腺癌这类亚群似乎保留了独特的生物学特征，但其能否作为乳腺癌的另一个新亚型，现有的研究证据尚不太充足，需要进一步研究来验证。因此，本文就HER-2低表达型乳腺癌的临床分子特征、药物治疗策略、预后方面的研究新进展进行综述，以期为HER-2低表达型乳腺癌的后续研究提供理论依据。
Abstract:
As one of the common malignant tumors in women,the incidence of breast cancer is always high.At present,breast cancer is divided into four molecular subtypes as luminal A,luminal B,human epidermal growth factor receptor-2(HER-2) overexpression and triple negative type.The concept of low expression of HER-2 was proposed in the 2021 guidelines for the diagnosis" and treatment of breast cancer.Although the low expression of HER-2 has been clearly defined,and the breast cancer with low expression of HER-2 retains unique biological characteristics,but the existing research evidence is not enough to confirm whether it can be used as another new subtype of breast cancer.Therefore,this paper reviews the recent advances on clinical molecular characteristics and drug treatment strategies of breast cancer with low expression of HER-2 in order to provide a theoretical basis for the follow-up research of breast cancer with low expression of HER-2.

参考文献/References:

［1］　SIEGEL R L,MILLER K D,FUCHS H E,et al.Cancer statistics,2021［J］.CA Cancer J Clin,2021,71:7-33.
［2］　DWIVEDI S,PUROHIT P,MISRA R,et al.Single cell omics of breast cancer:an update on characterization and diagnosis［J］.Indian J Clin Biochem,2019,34(1):3-18.
［3］　ELIDRISSI ERRAHHALI M,ELIDRISSI ERRAHHALI M,OUARZANE M,et al.First report on molecular breast cancer subtypes and their clinico-pathological characteristics in Eastern Morocco:series of 2 260 cases［J］.BMC Womens Health,2017,17(1):3.
［4］　GIEDT R J,PATHANIA D,CARLSON J C T,et al.Single-cell barcode analysis provides a rapid readout of cellular signaling pathways in clinical specimens［J］.Nat Commun,2018,9(1):4550.
［5］　HASHMI A,AIJAZ S,KHAN S,et al.Prognostic parameters of luminal A and luminal B intrinsic breast cancer subtypes of pakistani patients［J］.World J Surg Oncol,2018,16(1):1.
［6］　FULAWKA L,HALON A.Ki-67 evaluation in breast cancer:the daily diagnostic practice［J］.Indian J Pathol Microbiol，2017，60(2):177-184.
［7］　DI FIORE P P,PIERCE J H,KRAUS M H,et al.erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells［J］.Science,1987,237(4811):178-182.
［8］　YARDEN Y,SLIWKOWSKI M.Untangling the Erbb signalling network［J］.Nat Rev Mol Cell Biol,2001,2(2):127-137.
［9］　SAPINO A,GOIA M,RECUPERO D,et al.Current challenges for HER-2 testing in diagnostic pathology:state of the art and controversial issues［J］.Front Oncol,2013,3:129.
［10］　CHOONG G,CULLEN G,O′SULLIVAN C.Evolving standards of care and new challenges in the management of HER-2-positive breast cancer［J］.CA Cancer J Clin,2020,70(5):355-374.
［11］　DAWOOD S,BROGLIO K,BUZDAR A,et al.Prognosis of women with metastatic breast cancer by HER-2 status and trastuzumab treatment:an institutional-based review［J］.J Clin Oncol,2010,28(1):92-98.
［12］　刘月平,步宏,杨文涛.2019版中国乳腺癌HER2检测指南更新解读［J］.中华病理学杂志,2019，48(3):182-185.
LIU Y P,BU H,YANG W T.Interpretation of 2019 update of Chinese breast cancer HER2 detection guidelines［J］.Chin J Pathol,2019,48(3):182-185.
［13］　MODI S,PARK H,MURTHY R,et al.Antitumor activity and safety of Trastuzumab Deruxtecan in patients with HER-2-low-expressing advanced breast cancer:results from a phase Ib study［J］.J Clin Oncol,2020,38(17):1887-1896.
［14］　BANERJI U,VAN HERPEN C,SAURA C,et al.Trastuzumab duocarmazine in locally advanced and metastatic solid tumours and HER-2-expressing breast cancer:a phase 1 dose-escalation and dose-expansion study［J］.Lancet Oncol,2019,20(8):1124-1135.
［15］　黄香,蒋梦萍,包胜南,等.2021年CSCO《乳腺癌诊疗指南》更新要点解读［J］.中国肿瘤外科杂志,2021,13(3):209-215.
HUANG X，JIANG M P，BAO S N，et al.Update and interpretation of the 2021 Guidelines for the Diagnosis and Treatment of Breast Cancer by Chinese Society of Clinical Oncology（CSCO）［J］.Chin J Surg Oncol,2021,13(3):209-215.
［16］　ROSSI V,SAROTTO I,MAGGIOROTTO F,et al.Moderate immunohistochemical expression of HER-2 (2+) without HER-2 gene amplification is a negative prognostic factor in early breast cancer［J］.Oncologist，2012，17(11):1418-1425.
［17］　EGGEMANN H,IGNATOV T,BURGER E,et al.Moderate HER2 expression as a prognostic factor in hormone receptor positive breast cancer［J］.Endocr Relat Cancer，2015，22(5):725-733.
［18］　TARANTINO P,HAMILTON E,TOLANEY S,et al.HER-2 low breast cancer:pathological and clinical landscape［J］.J Clin Oncol,2020,38(17):1951-1962.
［19］　SHUI R,LIANG X,LI X,et al.Hormone receptor and human epidermal growth factor receptor 2 detection in invasive breast carcinoma:a retrospective study of 12 467 patients from 19 Chinese representative clinical centers［J］.Clin Breast Cancer,2020,20(1):e65-e74.
［20］　SCHETTINI F,CHIC N,BRASO-MARISTANY F,et al.Clinical,pathological,and PAM50 gene expression features of HER2-low breast cancer［J］.NPJ Breast Cancer,2021,7(1):1.
［21］　ZHANG G C,LIAO N,CHEN B,et al.Next-generation sequencing (NGS) identifies a new breast cancer subtype with HER2 low-amplification status as a candidate for targeted therapy［J］.J Clin Oncol,2020，38(15):553.
［22］　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,2021,22:1151-1161.
［23］　MIGLIETTA F,GRIGUOLO G,BOTTOSSO M,et al.4MO_PR HER2-low breast cancer:evolution from primary breast cancer to relapse［J］.Ann Oncol,2021,32:S23.
［24］　DIECI M V,MIGLIETTA F.HER2:a never ending story［J］.Lancet Oncol,2021,22(8),1051-1052.
［25］　ONSUM M D,GERETTI E,PARAGAS V,et al.Single-cell quantitative HER-2 measurement identifies heterogeneity and distinct subgroups within traditionally defined HER-2-positive patients［J］.Am J Pathol,2013,183(5):1446-1460.
［26］　PEREZ E A,ROMOND E H,SUMAN V J,et al.Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer:planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831［J］.J Clin Oncol,2014,32:3744-3752.
［27］　FEHRENBACHER L,CECCHINI R S,GEYER C E JR,et al.NSABP B-47/NRG oncology phase III randomized trial comparing adjuvant chemotherapy with or without trastuzumab in high-risk invasive breast cancer negative for HER-2 by FISH and with IHC 1+ or 2［J］.J Clin Oncol,2020,38:444-453.
［28］　GIANNI L,LlADO A,BIANCHI G,et al.Open-label,phase II,multicenter,randomized study of the efficacy and safety of two dose levels of Pertuzumab,a human epidermal growth factor receptor 2 dimerization inhibitor,in patients with human epidermal growth factor receptor 2-negative metastatic breast cancer［J］.J Clin Oncol,2010,28:1131-7.
［29］　KAN S,KOIDO S,OKAMOTO M,et al.Gemcitabine treatment enhances HER-2 expression in low HER-2-expressing breast cancer cells and enhances the antitumor effects of trastuzumab emtansine［J］.Oncol Rep,2015,34:504-510.
［30］　DI LEO A,GOMEZ H L,AZIZ Z,et al.Phase III,double-blind,randomized study comparing lapatinib plus paclitaxel with placebo plus paclitaxel as first-line treatment for metastatic breast cancer［J］.J Clin Oncol,2008,26:5544-5552.
［31］　PRESS M F,FINN R S,CAMEREON D,et al.HER-2 gene amplification,HER-2 and epidermal growth factor receptor mRNA and protein expression,and lapatinib efficacy in women with metastatic breast cancer［J］.Clin Cancer Res,2008,14:7861-7870.
［32］　OGITANI Y,AIDA T,HAGIHARA K,et al.DS-8201a,a novel HER2-targeting ADC with a novel DNA topoisomerase I inhibitor,demonstrates a promising antitumor efficacy with differentiation from T-DM1［J］.Clin Cancer Res,2016,22:5097-5108.
［33］　EIGER D,AGOSTINETTO E,SAUDE-CONDE R,et al.The exciting new field of HER2-Low breast cancer treatment［J］.Cancers (Basel),2021,13(5):1015.
［34］　IWATA H,TAMURA K,DOI T,et al.Trastuzumab deruxtecan (DS-8201a) in subjects with HER2-expressing solid tumors:long-term results of a large phase 1 study with multiple expansion cohorts［J］.J Clin Oncol,2018,36(15 Suppl) :2501-2501.
［35］　HAUSMAN D F,HAMILTON E P,BEERAM M,et al.Phase 1 study of ZW25,a bispecific anti-HER-2 antibody,in patients with advanced HER-2-expressing cancers［J］.J Clin Oncol,2017,35(4 Suppl):TPS215-TPS215.
［36］　CLIFTON G T,PEACE K M,HOLMES J P,et al.Initial safety analysis of a randomized phase II trial of nelipepimut-S+GM-CSF and trastuzumab compared to trastuzumab alone to prevent recurrence in breast cancer patients with HER2 low-expressing tumors［J］.Clin Immunol,2019,201:48-54.
［37］　CLIFTON G,HALE D,VREELAND T,et al.Results of a randomized phase IIb trial of Nelipepimut-S+Trastuzumab versus Trastuzumab to prevent recurrences in patients with high-risk HER-2 low-expressing breast cancer［J］.Clin Cancer Res,2020,26(11):2515-2523.
［38］　ARPINO G,WIECHMANN L,OSBORNE C K,et al.Crosstalk between the estrogen receptor and the HER tyrosine kinase receptor family:molecular mechanism and clinical implications for endocrine therapy resistance［J］.Endocr Rev,2008,29(2):217-233.
［39］　SHOU J,MASSARWEH S,OSBORNE C K,et al.Mechanisms of tamoxifen resistance:increased estrogen receptor-HER2/neu cross-talk in ER/HER2-positive breast cancer［J］.J Natl Cancer Inst,2004,96(12):926-935.
［40］　GILCREASE M Z,WOODWARD W A,NICOLAS M M,et al.Even low-level HER-2 expression may be associated with worse outcome in node-positive breast cancer［J］.Am J Surg Pathol,2009,33(5):759-767.
［41］　IGNATOV T,EGGEMANN H,BURGER E,et al.Moderate level of HER-2 expression and its prognostic significance in breast cancer with intermediate grade［J］.Breast Cancer Res Treat,2015,151(2):357-364.
［42］　KIM M H,KIM G M,KIM J H,et al.Intermediate HER2 expression is associated with poor prognosis in estrogen receptor-positive breast cancer patients aged 55 years and older［J］.Breast Cancer Res Treat,2020,179:687-697.
（

相似文献/References:

[1]张光谋,吴俊琢,徐振平,等.抗细胞凋亡基因bcl一2在乳腺癌中的表达[J].新乡医学院学报,2001,18(03):160.
[2]刘玉生 ． 万里,李森恺.乳腺癌切除即期乳房再造[J].新乡医学院学报,2001,18(01):023.
[3]王承正,张锦瑜,邱树升,等.C—erbB一2与ER、PS一2在乳腺癌中的表达及其临床相关性[J].新乡医学院学报,2003,20(05):324.
[4]王承正,张锦瑜,邱树升,等.C2erbB22 与ER、PS22 在乳腺癌中的表达及其临床相关性[J].新乡医学院学报,2003,20(05):324.
[5]王志民,段西华,祁天义,等.多点皮瓣固定法预防乳腺癌术后皮下积液效果观察 [J].新乡医学院学报,2007,24(03):287.
[6]郭兰青.乳腺癌患者生活质量影响因素[J].新乡医学院学报,2008,25(06):637.
[7]曹兴玥,赵庆伟,靳艳,等.CD44和nm23在乳腺浸润性导管癌中的表达及其与淋巴结转移的关系[J].新乡医学院学报,2011,28(01):042.
[8]靳艳,曹兴玥,赵庆伟,等.CD62P在人乳腺癌组织中的表达及其与淋巴结转移的关系[J].新乡医学院学报,2011,28(01):045.
[9]王　乐,王静萱,张清媛.乳腺癌骨转移靶向治疗进展[J].新乡医学院学报,2015,32(09):887.
[10]薛会朝,王　雷,李　建,等.乳腺癌干细胞及其分化细胞中雌激素受体、孕激素受体和人类表皮生长因子受体2的表达[J].新乡医学院学报,2017,34(5):361.[doi:10.7683/xxyxyxb.2017.05.004]
　XUE Hui-chao,WANG Lei,LI Jian,et al.Expression of estrogen receptor，progesterone receptor and human epidermal growth factor receptor 2 in breast cancer stem cells and their differentiated cells[J].Journal of Xinxiang Medical University,2017,34(6):361.[doi:10.7683/xxyxyxb.2017.05.004]
[11]杨绍英,刘朝荣,张志刚,等.乳腺癌新辅助化学治疗前后雌激素受体、乳激素受体、Ki-67抗原和人类表皮生长因子受体-2的表达[J].新乡医学院学报,2017,34(2):125.[doi:10.7683/xxyxyxb.2017.02.012]
　YANG Shao-ying,LIU Chao-rong,ZHANG Zhi-gang,et al.Expressions of estrogen receptor，progestin recetor，Ki-67 antigen，and human epidermal growth factor receptor 2 before and after neoadjuvant chemotherapy in patients with breast cancer[J].Journal of Xinxiang Medical University,2017,34(6):125.[doi:10.7683/xxyxyxb.2017.02.012]

更新日期/Last Update: 2023-06-05