• Login
    View Item 
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Circulating tumor DNA in HER2 amplified breast cancer: a translational research substudy of the NeoALTTO phase 3 trial

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Rothe, F
    Silva, M
    Venet, D
    Campbell, C
    Bradbury, I
    Rouas, G
    de Azambuja, E
    Maetens, M
    Fumagalli, D
    Rodrik-Outmezguine, V
    Di Cosimo, S
    Rosa, D
    Chia, S
    Wardley, Andrew M
    Ueno, T
    Janni, W
    Huober, J
    Baselga, J
    Piccart, M
    Loi, S
    Sotiriou, C
    Dawson, S
    Ignatiadis, M
    Affiliation
    Breast Cancer Translational Research Laboratory, Queen's University Belfast
    Issue Date
    2019
    
    Metadata
    Show full item record
    Abstract
    PURPOSE: In the neoadjuvant treatment (NAT) setting, dual human epidermal growth factor receptor 2 (HER2) targeted therapy is associated with increased pathological complete response (pCR) rates compared to each therapy alone. Biomarkers allowing to predict treatment response during NAT are needed. We aim to evaluate whether circulating tumor DNA (ctDNA) is associated with response to anti-HER2 targeted therapy. EXPERIMENTAL DESIGN: Plasma DNA collected before NAT, at week2 and before surgery from patients enrolled in the NeoALTTOtrialwas assessed using digital PCR for PIK3CA and TP53 mutation detection. RESULTS: A total of 69 of 455 (15.2%) patients had a PIK3CA and/or TP53 mutation detected in the baseline tumor sample and evaluable ctDNA results from baseline samples. CtDNA was detected in 41%, 20% and 5% patients before NAT, at week 2 and before surgery respectively. CtDNA detection before NAT was significantly associated with older age and ER-negative status. CtDNA detection before NAT was associated with decreased odds of achieving pCR (OR 0.15, 95%CI 0.034-0.7, p=0.0089) but not with event-free survival (EFS). Analyses for EFS were underpowered. Interestingly, the patients with HER2 enriched subtype tumors and undetectable ctDNA at baseline had the highest pCR rates. By contrast, patients with persistent ctDNA detection at baseline and week 2 had the lowest rate of pCR. CONCLUSIONS: CtDNA detection before neoadjuvant anti-HER2 therapies is associated with decreased pCR rates. Interestingly, patients with HER2 enriched tumors and undetectable ctDNA at baseline had the highest pCR rates, therefore appearing as the best candidates for treatment de-escalation strategies.
    Citation
    Rothe F, Silva MJ, Venet D, Campbell C, Bradbury I, Rouas G, et al. Circulating tumor DNA in HER2 amplified breast cancer: a translational research substudy of the NeoALTTO phase 3 trial. Clin Cancer Res. 2019.
    Journal
    Clinical Cancer Research
    URI
    http://hdl.handle.net/10541/621781
    DOI
    10.1158/1078-0432.CCR-18-2521
    PubMed ID
    30862692
    Additional Links
    https://dx.doi.org/10.1158/1078-0432.CCR-18-2521
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1158/1078-0432.CCR-18-2521
    Scopus Count
    Collections
    All Christie Publications

    entitlement

    Related articles

    • RNA Sequencing to Predict Response to Neoadjuvant Anti-HER2 Therapy: A Secondary Analysis of the NeoALTTO Randomized Clinical Trial.
    • Authors: Fumagalli D, Venet D, Ignatiadis M, Azim HA Jr, Maetens M, Rothé F, Salgado R, Bradbury I, Pusztai L, Harbeck N, Gomez H, Chang TW, Coccia-Portugal MA, Di Cosimo S, de Azambuja E, de la Peña L, Nuciforo P, Brase JC, Huober J, Baselga J, Piccart M, Loi S, Sotiriou C
    • Issue date: 2017 Feb 1
    • Circulating tumor cells and response to neoadjuvant paclitaxel and HER2-targeted therapy: a sub-study from the NeoALTTO phase III trial.
    • Authors: Azim HA Jr, Rothé F, Aura CM, Bavington M, Maetens M, Rouas G, Gebhart G, Gamez C, Eidtmann H, Baselga J, Piccart-Gebhart M, Ellis C, Vuylsteke P, Cure H, Domont J, Ferro A, Toral-Peña JC, de Azambuja E, Sotiriou C, Di Cosimo S, Ignatiadis M
    • Issue date: 2013 Dec
    • ctDNA dynamics: a novel indicator to track resistance in metastatic breast cancer treated with anti-HER2 therapy.
    • Authors: Ma F, Zhu W, Guan Y, Yang L, Xia X, Chen S, Li Q, Guan X, Yi Z, Qian H, Yi X, Xu B
    • Issue date: 2016 Oct 4
    • Patient-Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.
    • Authors: Riva F, Bidard FC, Houy A, Saliou A, Madic J, Rampanou A, Hego C, Milder M, Cottu P, Sablin MP, Vincent-Salomon A, Lantz O, Stern MH, Proudhon C, Pierga JY
    • Issue date: 2017 Mar
    • PIK3CA mutations are associated with lower rates of pathologic complete response to anti-human epidermal growth factor receptor 2 (her2) therapy in primary HER2-overexpressing breast cancer.
    • Authors: Loibl S, von Minckwitz G, Schneeweiss A, Paepke S, Lehmann A, Rezai M, Zahm DM, Sinn P, Khandan F, Eidtmann H, Dohnal K, Heinrichs C, Huober J, Pfitzner B, Fasching PA, Andre F, Lindner JL, Sotiriou C, Dykgers A, Guo S, Gade S, Nekljudova V, Loi S, Untch M, Denkert C
    • Issue date: 2014 Oct 10
    DSpace software (copyright © 2002 - 2019)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.