Clonal replacement and heterogeneity in breast tumors treated with neoadjuvant HER2-targeted therapy

被引：43

作者：

Caswell-Jin, Jennifer L. ^{[1
,3
]}

McNamara, Katherine ^{[1
,2
,3
]}

Reiter, Johannes G. ^{[4
]}

Sun, Ruping ^{[1
,2
,3
]}

Hu, Zheng ^{[1
,2
,3
]}

Ma, Zhicheng ^{[1
,2
,3
]}

Ding, Jie ^{[1
,2
,3
]}

Suarez, Carlos J. ^{[5
]}

Tilk, Susanne ^{[6
]}

Raghavendra, Akshara ^{[7
]}

Forte, Victoria ^{[8
,9
]}

Chin, Suet-Feung ^{[10
]}

Bardwell, Helen ^{[10
]}

Provenzano, Elena ^{[11
,12
]}

Caldas, Carlos ^{[10
]}

Lang, Julie ^{[9
,13
]}

West, Robert ^{[5
]}

Tripathy, Debu ^{[7
]}

Press, Michael F. ^{[9
,14
]}

Curtis, Christina ^{[1
,2
,3
]}

机构：

[1] Stanford Univ, Dept Med, Sch Med, Div Oncol, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA

[4] Stanford Univ, Sch Med, Dept Radiol, Canary Ctr Canc Early Detect, Stanford, CA 94305 USA

[5] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA

[6] Stanford Univ, Dept Biol, Stanford, CA 94305 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA

[8] Maimonides Hosp, Brooklyn, NY 11219 USA

[9] Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA

[10] Univ Cambridge, Dept Oncol, Canc Res UK Cambridge Inst, Cambridge CB2 0RE, England

[11] Cambridge Univ Hosp NHS Fdn Trust, Cambridge Expt Canc Med Ctr, Cambridge CB2 0QQ, England

[12] Cambridge Univ Hosp NHS Fdn Trust, NIHR Cambridge Biomed Res Ctr, Cambridge CB2 0QQ, England

[13] Univ Southern Calif, Keck Sch Med, Dept Surg, Los Angeles, CA 90333 USA

[14] Univ Southern Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

美国国家卫生研究院; 奥地利科学基金会;

关键词：

WHOLE-GENOME; MUTATIONAL PROCESSES; RESIDUAL DISEASE; CANCER; CHEMOTHERAPY; REVEALS; EVOLUTION; ARCHITECTURE; POPULATIONS; BIOMARKERS;

D O I：

10.1038/s41467-019-08593-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Genomic changes observed across treatment may result from either clonal evolution or geographically disparate sampling of heterogeneous tumors. Here we use computational modeling based on analysis of fifteen primary breast tumors and find that apparent clonal change between two tumor samples can frequently be explained by pre-treatment heterogeneity, such that at least two regions are necessary to detect treatment-induced clonal shifts. To assess for clonal replacement, we devise a summary statistic based on whole-exome sequencing of a pre-treatment biopsy and multi-region sampling of the post-treatment surgical specimen and apply this measure to five breast tumors treated with neoadjuvant HER2-targeted therapy. Two tumors underwent clonal replacement with treatment, and mathematical modeling indicates these two tumors had resistant subclones prior to treatment and rates of resistance-related genomic changes that were substantially larger than previous estimates. Our results provide a needed framework to incorporate primary tumor heterogeneity in investigating the evolution of resistance.

引用

页数：12

共 50 条

[31] The tumor immune microenvironment remodeling and response to HER2-targeted therapy in HER2-positive advanced gastric cancer [J].

Jiang, Lei ;

Zhao, Xingwang ;

Li, Yilin ;

Hu, Yajie ;

Sun, Yu ;

Liu, Shengde ;

Zhang, Zizhen ;

Li, Yanyan ;

Feng, Xujiao ;

Yuan, Jiajia ;

Li, Jian ;

Zhang, Xiaotian ;

Chen, Yang ;

Shen, Lin .

IUBMB LIFE, 2024, 76 (07) :420-436

[32] Cutaneous Adnexal Adenocarcinoma: Genomic Analysis and Successful HER2-targeted Therapy of Metastatic Disease [J].

Hirano-Lotman, Yui ;

Ishida, Yoshihiro ;

Endo, Yuichiro ;

Ogawa, Seishi ;

Kabashima, Kenji .

ACTA DERMATO-VENEREOLOGICA, 2023, 103

[33] Complete pathological response in patients with HER2 positive breast cancer treated with neoadjuvant therapy in Colombia [J].

Rodriguez, Mauricio ;

Gonzalez, Diego M. ;

El-Sharkawy, Farah ;

Castano, Mileny ;

Madrid, Jorge .

BIOMEDICA, 2023, 43 (03) :396-405

[34] A pan-cancer analysis of HER2 index revealed transcriptional pattern for precise selection of HER2-targeted therapy [J].

Li, Ziteng ;

Chen, Siyuan ;

Feng, Wanjing ;

Luo, Yixiao ;

Lai, Hongyan ;

Li, Qin ;

Xiu, Bingqiu ;

Li, Yuchen ;

Li, Yan ;

Huang, Shenglin ;

Zhu, Xiaodong .

EBIOMEDICINE, 2020, 62

[35] Loss of HER2-positivity following neoadjuvant targeted therapy for breast cancer is not associated with inferior oncologic outcomes [J].

Wetzel, Catherine L. ;

Sutton, Thomas L. ;

Gardiner, Stuart ;

Farinola, Maryam ;

Johnson, Nathalie ;

Garreau, Jennifer R. .

JOURNAL OF SURGICAL ONCOLOGY, 2021, 124 (08) :1224-1234

[36] HER2-Targeted Polyinosine/Polycytosine Therapy Inhibits Tumor Growth and Modulates the Tumor Immune Microenvironment [J].

Zigler, Maya ;

Shir, Alexei ;

Joubran, Salim ;

Sagalov, Anna ;

Klein, Shoshana ;

Edinger, Nufar ;

Lau, Jeffrey ;

Yu, Shang-Fan ;

Mizraji, Gabriel ;

Levin, Anat Globerson ;

Sliwkowski, Mark X. ;

Levitzki, Alexander .

CANCER IMMUNOLOGY RESEARCH, 2016, 4 (08) :688-697

[37] Identification of novel pathways linking epithelial-to-mesenchymal transition with resistance to HER2-targeted therapy [J].

Creedon, Helen ;

Gomez-Cuadrado, Laura ;

Tarnauskaite, Zygimante ;

Balla, Jozef ;

Canel, Marta ;

MacLeod, Kenneth G. ;

Serrels, Bryan ;

Fraser, Craig ;

Unciti-Broceta, Asier ;

Tracey, Natasha ;

Le Bihan, Thierry ;

Klinowska, Teresa ;

Sims, Andrew H. ;

Byron, Adam ;

Brunton, Valerie G. .

ONCOTARGET, 2016, 7 (10) :11539-11552

[38] Nomogram to predict pathologic complete response in HER2-positive breast cancer treated with neoadjuvant systemic therapy [J].

Fujii, Takeo ;

Kogawa, Takahiro ;

Wu, Jimin ;

Sahin, Aysegul A. ;

Liu, Dian D. ;

Chavez-MacGregor, Mariana ;

Giordano, Sharon H. ;

Raghavendra, Akshara ;

Murthy, Rushmy K. ;

Tripathy, Debu ;

Shen, Yu ;

Yamal, Jose-Miguel ;

Ueno, Naoto T. .

BRITISH JOURNAL OF CANCER, 2017, 116 (04) :509-514

[39] Lung cancer patients with HER2 mutations treated with chemotherapy and HER2-targeted drugs: results from the European EUHER2 cohort [J].

Mazieres, J. ;

Barlesi, F. ;

Filleron, T. ;

Besse, B. ;

Monnet, I. ;

Beau-Faller, M. ;

Peters, S. ;

Dansin, E. ;

Frueh, M. ;

Pless, M. ;

Rosell, R. ;

Wislez, M. ;

Fournel, P. ;

Westeel, V. ;

Cappuzzo, F. ;

Cortot, A. ;

Moro-Sibilot, D. ;

Milia, J. ;

Gautschi, O. .

ANNALS OF ONCOLOGY, 2016, 27 (02) :281-286

[40] Not All HER2-Positive Breast Cancers Are the Same: Intratumoral Heterogeneity, Low-Level HER2 Amplification, and Their Impact on Neoadjuvant Therapy Response [J].

Dai, Wenli ;

Navolotskaia, Olga ;

Fine, Jeffrey L. ;

Harinath, Lakshmi ;

Motanagh, Samaneh A. ;

Villatoro, Tatiana M. ;

Bhargava, Rohit ;

Clark, Beth Z. ;

Yu, Jing .

MODERN PATHOLOGY, 2025, 38 (07)

← 1 2 3 4 5 →