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  • Haugen, Mads H.Oslo university hospital,Norwegian Radium Hospital (author)

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

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021
  • 21 s.

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  • LIBRIS-ID:oai:lup.lub.lu.se:f7ce7082-c3b7-49a6-a1d0-2d347ea135a0
  • https://lup.lub.lu.se/record/f7ce7082-c3b7-49a6-a1d0-2d347ea135a0URI
  • https://doi.org/10.1200/PO.20.00086DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

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  • 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.

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  • Lingjærde, Ole ChristianNorwegian Radium Hospital,University of Oslo (author)
  • Hedenfalk, IngridLund University,Lunds universitet,Bröst- och ovarialcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Breast and Ovarian Cancer Genomics,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-ifa (author)
  • Garred, ØysteinNorwegian Radium Hospital,Oslo university hospital (author)
  • Borgen, ElinOslo university hospital,Norwegian Radium Hospital (author)
  • Loman, NiklasLund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Bröst/ovarialcancer,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Breast/ovarian cancer,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital(Swepub:lu)onk-nlo (author)
  • Hatschek, ThomasKarolinska University Hospital (author)
  • Børresen-Dale, Anne LiseUniversity of Oslo,Norwegian Radium Hospital,Oslo university hospital (author)
  • Naume, BjørnUniversity of Oslo,Oslo university hospital (author)
  • Mills, Gordon B.Oregon Health & Science University (author)
  • Mælandsmo, Gunhild M.UiT The Arctic University of Norway, Tromsø,Norwegian Radium Hospital,Oslo university hospital (author)
  • Engebraaten, OlavOslo university hospital,Norwegian Radium Hospital,University of Oslo (author)
  • Oslo university hospitalNorwegian Radium Hospital (creator_code:org_t)

Related titles

  • In:JCO Precision Oncology5, s. 286-3062473-4284

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