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Title: | Development and validation of the new HER2DX assay for predicting pathological response and survival outcome in early-stage HER2-positive breast cancer |
Author: | Prat Aparicio, Aleix Guarneri, Valentina Pascual, Tomás Brasó Maristany, Fara Sanfeliu, Esther Paré Brunet, Laia Schettini, Francesco Martínez, Debora Jares Gerboles, Pedro Griguolo, Gaia Dieci, Maria Vittoria Cortés, Javier Llombart Cussac, Antonio Conte, Benedetta Marín Aguilera, Mercedes Chic Ruché, Núria Puig Butillé, Joan Anton Martínez, Antonio Galván, Patricia Tsai, Yi-Hsuan González Farré, Blanca Mira, Aurea Vivancos, Ana Villagrasa, Patricia Parker, Joel S. Conte, Pierfranco Perou, Charles M. |
Keywords: | Expressió gènica Càncer de mama Immunitat cel·lular Tractament adjuvant del càncer Pronòstic mèdic Factors de risc en les malalties Avaluació del risc per la salut Gene expression Breast cancer Cellular immunity Adjuvant treatment of cancer Prognosis Risk factors in diseases Health risk assessment |
Issue Date: | 3-Jan-2022 |
Publisher: | Elsevier |
Abstract: | Background: Both clinical and genomic data independently predict survival and treatment response in early-stage HER2-positive breast cancer. Here we present the development and validation of a new HER2DX risk score, and a new HER2DX pathological complete response (pCR) score, both based on a 27-gene expression plus clinical feature-based classifier. Methods: HER2DX is a supervised learning algorithm incorporating tumour size, nodal staging, and 4 gene expression signatures tracking immune infiltration, tumour cell proliferation, luminal differentiation, and the expression of the HER2 amplicon, into a single score. 434 HER2-positive tumours from the Short-HER trial were used to train a prognostic risk model; 268 cases from an independent cohort were used to verify the accuracy of the HER2DX risk score. In addition, 116 cases treated with neoadjuvant anti-HER2-based chemotherapy were used to train a predictive model of pathological complete response (pCR); two independent cohorts of 91 and 67 cases were used to verify the accuracy of the HER2DX pCR likelihood score. Five publicly available independent datasets with >1,000 patients with early-stage HER2-positive disease were also analysed. Findings: In Short-HER, HER2DX variables were associated with good risk outcomes (i.e., immune, and luminal) and poor risk outcomes (i.e., proliferation, and tumour and nodal staging). In an independent cohort, continuous HER2DX risk score was significantly associated with disease-free survival (DFS) (p=0·002); the 5-year DFS in the low-risk group was 97·4% (94·4-100·0%). For the neoadjuvant pCR predictor training cohort, HER2DX variables were associated with pCR (i.e., immune, proliferation and HER2 amplicon) and non-pCR (i.e., luminal, and tumour and nodal staging). In both independent test set cohorts, continuous HER2DX pCR likelihood score was significantly associated with pCR (p<0·0001). A weak negative correlation was found between the HER2DX risk score versus the pCR score (correlation coefficient -0·19). Interpretation: The two HER2DX tests provide accurate estimates of the risk of recurrence, and the likelihood to achieve a pCR, in early-stage HER2-positive breast cancer. Funding: This study received funding from Reveal Genomics, IDIBAPS and the University of Padova. |
Note: | Reproducció del document publicat a: https://doi.org/10.1016/j.ebiom.2021.103801 |
It is part of: | EBioMedicine, 2022, vol. 75, num. 103801 |
URI: | http://hdl.handle.net/2445/194403 |
Related resource: | https://doi.org/10.1016/j.ebiom.2021.103801 |
ISSN: | 2352-3964 |
Appears in Collections: | Articles publicats en revistes (Medicina) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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