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

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

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

Lingjærde, Ole Christian (author): Norwegian Radium Hospital,University of Oslo

Hedenfalk, Ingrid (author): Lund 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

Garred, Øystein (author): Norwegian Radium Hospital,Oslo university hospital

Borgen, Elin (author): Oslo university hospital,Norwegian Radium Hospital

Loman, Niklas (author): Lund 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

Hatschek, Thomas (author): Karolinska University Hospital

Børresen-Dale, Anne Lise (author): University of Oslo,Norwegian Radium Hospital,Oslo university hospital

Naume, Bjørn (author): University of Oslo,Oslo university hospital

Mills, Gordon B. (author): Oregon Health & Science University

Mælandsmo, Gunhild M. (author): UiT The Arctic University of Norway, Tromsø,Norwegian Radium Hospital,Oslo university hospital

Engebraaten, Olav (author): Oslo university hospital,Norwegian Radium Hospital,University of Oslo

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2021
2021
English 21 s.
In: JCO Precision Oncology. - 2473-4284. ; 5, s. 286-306

Related links:: http://dx.doi.org/10... (free); show more...; https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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By the author/editor: Haugen, Mads H.; Lingjærde, Ole C ...; Hedenfalk, Ingri ...; Garred, Øystein; Borgen, Elin; Loman, Niklas; show more...; Hatschek, Thomas; Børresen-Dale, A ...; Naume, Bjørn; Mills, Gordon B.; Mælandsmo, Gunhi ...; Engebraaten, Ola ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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