TY - JOUR
T1 - Protein signature predicts response to neoadjuvant treatment with chemotherapy and bevacizumab in HER2-negative breast cancers
AU - Haugen, Mads H.
AU - Lingjærde, Ole Christian
AU - Hedenfalk, Ingrid
AU - Garred, Øystein
AU - Borgen, Elin
AU - Loman, Niklas
AU - Hatschek, Thomas
AU - Børresen-Dale, Anne Lise
AU - Naume, Bjørn
AU - Mills, Gordon B.
AU - Mælandsmo, Gunhild M.
AU - Engebraaten, Olav
N1 - Funding Information:
The authors would like to acknowledge the financial support from the Norwegian South-Eastern Regional Health Authorities (Project # 2019081 to M.H.H.), The Norwegian Cancer Society (Project # 198091 to O.E. and M.H.H.), the National Cancer Institute at the National Institutes of Health (NCI #CA217842 to G.B.M. and #CA16672 to the RPPA Core Facility at MD Anderson Cancer Center), Susan G. Komen (SAC110052 to G.B.M.), and Breast Cancer Research Foundation (BCRF-18-110 to G.B.M.). The NeoAva clinical study was cosponsored by Roche Norway and Sanofi-Aventis.
Publisher Copyright:
Copyright © 2021 American Society of Clinical Oncology. All rights reserved.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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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U2 - 10.1200/PO.20.00086
DO - 10.1200/PO.20.00086
M3 - Article
AN - SCOPUS:85101718935
SN - 2473-4284
VL - 5
SP - 286
EP - 306
JO - JCO Precision Oncology
JF - JCO Precision Oncology
ER -