ub.xmlui.mirage2.page-structure.muninLogoub.xmlui.mirage2.page-structure.openResearchArchiveLogo
    • EnglishEnglish
    • norsknorsk
  • Velg spraaknorsk 
    • EnglishEnglish
    • norsknorsk
  • Administrasjon/UB
Vis innførsel 
  •   Hjem
  • Det helsevitenskapelige fakultet
  • Institutt for medisinsk biologi
  • Artikler, rapporter og annet (medisinsk biologi)
  • Vis innførsel
  •   Hjem
  • Det helsevitenskapelige fakultet
  • Institutt for medisinsk biologi
  • Artikler, rapporter og annet (medisinsk biologi)
  • Vis innførsel
JavaScript is disabled for your browser. Some features of this site may not work without it.

Protein signature predicts response to neoadjuvant treatment with chemotherapy and bevacizumab in HER2-negative breast cancers

Permanent lenke
https://hdl.handle.net/10037/24205
DOI
https://doi.org/10.1200/PO.20.00086
Thumbnail
Åpne
article.pdf (1.440Mb)
Publisert versjon (PDF)
Dato
2021-01-28
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Forfatter
Haugen, Mads Haugland; Lingjærde, Ole Christian; Hedenfalk, Ingrid; Garred, Øystein; Borgen, Elin; Loman, Niklas; Hatschek, Thomas; Børresen-Dale, Anne-Lise; Naume, Bjørn; Mills, Gordon B.; Mælandsmo, Gunhild Mari; Engebråten, Olav
Sammendrag

PURPOSE: Antiangiogenic therapy using bevacizumab has proven effective for a number of cancers; however, in breast cancer (BC), there is an unmet need to identify patients who benefit from such treatment.

PATIENTS AND METHODS: In the NeoAva phase II clinical trial, patients (N = 132) with large (≥ 25 mm) human epidermal growth factor receptor 2 (HER2)-negative primary tumors were randomly assigned 1:1 to treatment with neoadjuvant chemotherapy (CTx) alone or in combination with bevacizumab (Bev plus CTx). The ratio of the tumor size after relative to before treatment was calculated into a continuous response scale. Tumor biopsies taken prior to neoadjuvant treatment were analyzed by reverse-phase protein arrays (RPPA) for expression levels of 210 BC-relevant (phospho-) proteins. Lasso regression was used to derive a predictor of tumor shrinkage from the expression of selected proteins prior to treatment.

RESULTS: We identified a nine-protein signature score named vascular endothelial growth factor inhibition response predictor (ViRP) for use in the Bev plus CTx treatment arm able to predict with accuracy pathologic complete response (pCR) (area under the curve [AUC] = 0.85; 95% CI, 0.74 to 0.97) and low residual cancer burden (RCB 0/I) (AUC = 0.80; 95% CI, 0.68 to 0.93). The ViRP score was significantly lower in patients with pCR (P < .001) and in patients with low RCB (P < .001). The ViRP score was internally validated on mRNA data and the resultant surrogate mRNA ViRP score significantly separated the pCR patients (P = .016). Similarly, the mRNA ViRP score was validated (P < .001) in an independent phase II clinical trial (PROMIX).

CONCLUSION: Our ViRP score, integrating the expression of nine proteins and validated on mRNA data both internally and in an independent clinical trial, may be used to increase the likelihood of benefit from treatment with bevacizumab combined with chemotherapy in patients with HER2-negative BC.

Forlag
American Society of Clinical Oncology
Sitering
Haugen, Lingjærde, Hedenfalk, Garred, Borgen, Loman, Hatschek, Børresen-Dale, Naume, Mills, Mælandsmo, Engebråten. Protein signature predicts response to neoadjuvant treatment with chemotherapy and bevacizumab in HER2-negative breast cancers. JCO Precision Oncology (JCO PO). 2021;5:286-306
Metadata
Vis full innførsel
Samlinger
  • Artikler, rapporter og annet (medisinsk biologi) [1103]
Copyright 2021 The Author(s)

Bla

Bla i hele MuninEnheter og samlingerForfatterlisteTittelDatoBla i denne samlingenForfatterlisteTittelDato
Logg inn

Statistikk

Antall visninger
UiT

Munin bygger på DSpace

UiT Norges Arktiske Universitet
Universitetsbiblioteket
uit.no/ub - munin@ub.uit.no

Tilgjengelighetserklæring