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dc.contributor.authorHaugen, Mads Haugland
dc.contributor.authorLingjærde, Ole Christian
dc.contributor.authorHedenfalk, Ingrid
dc.contributor.authorGarred, Øystein
dc.contributor.authorBorgen, Elin
dc.contributor.authorLoman, Niklas
dc.contributor.authorHatschek, Thomas
dc.contributor.authorBørresen-Dale, Anne-Lise
dc.contributor.authorNaume, Bjørn
dc.contributor.authorMills, Gordon B.
dc.contributor.authorMælandsmo, Gunhild Mari
dc.contributor.authorEngebråten, Olav
dc.date.accessioned2022-03-01T12:50:43Z
dc.date.available2022-03-01T12:50:43Z
dc.date.issued2021-01-28
dc.description.abstract<p>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. <p>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. <p>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). <p>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.en_US
dc.identifier.citationHaugen, 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;5:286-306en_US
dc.identifier.cristinIDFRIDAID 2003074
dc.identifier.doi10.1200/PO.20.00086
dc.identifier.issn2473-4284
dc.identifier.urihttps://hdl.handle.net/10037/24205
dc.language.isoengen_US
dc.publisherAmerican Society of Clinical Oncologyen_US
dc.relation.journalJCO Precision Oncology (JCO PO)
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.titleProtein signature predicts response to neoadjuvant treatment with chemotherapy and bevacizumab in HER2-negative breast cancersen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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