Dataset Information

Immune Effective Score as a Predictor of Response to Neoadjuvant Trastuzumab Therapy and a Prognostic Indicator for HER2-Positive Breast Cancer.

ABSTRACT:

Background

HER2-positive breast cancer (BC) is a highly aggressive phenotype. The role of the host immune features in predictive response to anti-HER2 therapies and prognosis in BC has already been suggested. We aimed to develop a predictive and prognostic model and examine its relevance to the clinical outcomes of patients with HER2-positive BC.

Methods

Immune effective score (IES) was constructed using principal component analysis algorithms. A bioinformatic analysis using four independent cohorts (GSE66305, n = 88; GSE130786, n = 110; TCGA, n = 123; METABRIC, n = 236) established associations between IES and clinical outcomes.

Results

Genes associated with neoadjuvant trastuzumab therapy response were enriched in pathways related to antitumor immune activities. IES was demonstrated to be a predictive biomarker to neoadjuvant trastuzumab therapy benefits (GSE66305: area under the curve (AUC) = 0.804; GSE130786: AUC = 0.704). In addition, IES was identified as an independent prognostic factor for overall survival (OS) in the TCGA cohort (p = 0.036, hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.449-0.97) and METABRIC cohort (p = 0.037, HR: 0.9, 95% CI: 0.81-0.99).

Conclusion

IES has a predictive value for response to neoadjuvant trastuzumab therapy and independent prognostic value for HER2-positive breast cancer.

SUBMITTER: Wu X

PROVIDER: S-EPMC8775173 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Immune Effective Score as a Predictor of Response to Neoadjuvant Trastuzumab Therapy and a Prognostic Indicator for HER2-Positive Breast Cancer.

Wu Xueying X Zhang Chenyang C Zhang Henghui H

Current oncology (Toronto, Ont.) 20220110 1

<h4>Background</h4>HER2-positive breast cancer (BC) is a highly aggressive phenotype. The role of the host immune features in predictive response to anti-HER2 therapies and prognosis in BC has already been suggested. We aimed to develop a predictive and prognostic model and examine its relevance to the clinical outcomes of patients with HER2-positive BC.<h4>Methods</h4>Immune effective score (IES) was constructed using principal component analysis algorithms. A bioinformatic analysis using four ...[more]

PMID: 35049700

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Project description:BackgroundOverexpression of human epidermal growth factor receptor 2 (HER2) caused by HER2 gene amplification is a driver in breast cancer tumorigenesis. We aimed to investigate the prognostic significance of manual scoring and digital image analysis (DIA) algorithm assessment of HER2 copy numbers and HER2/CEP17 ratios, along with ERBB2 mRNA levels among early-stage HER2-positive breast cancer patients treated with trastuzumab.MethodsThis retrospective study comprised 371 early HER2-positive breast cancer patients treated with adjuvant trastuzumab, with HER2 re-testing performed on whole tumor sections. Digitized tumor tissue slides were manually scored and assessed with uPath HER2 Dual ISH image analysis, breast algorithm. Targeted ERBB2 mRNA levels were assessed by the Xpert® Breast Cancer STRAT4 Assay. HER2 copy number and HER2/CEP17 ratio from in situ hybridization assessment, along with ERBB2 mRNA levels, were explored in relation to recurrence-free survival (RFS).ResultsThe analysis showed that patients with tumors with the highest and lowest manually counted HER2 copy number levels had worse RFS than those with intermediate levels (HR = 2.7, CI 1.4-5.3, p = 0.003 and HR = 2.1, CI 1.1-3.9, p = 0.03, respectively). A similar trend was observed for HER2/CEP17 ratio, and the DIA algorithm confirmed the results. Moreover, patients with tumors with the highest and the lowest values of ERBB2 mRNA had a significantly worse prognosis (HR = 2.7, CI 1.4-5.1, p = 0.003 and HR = 2.8, CI 1.4-5.5, p = 0.004, respectively) compared to those with intermediate levels.ConclusionsOur findings suggest that the association between any of the three HER2 biomarkers and RFS was nonlinear. Patients with tumors with the highest levels of HER2 gene amplification or ERBB2 mRNA were associated with a worse prognosis than those with intermediate levels, which is of importance to investigate in future clinical trials studying HER2-targeted therapy.

Dataset Information

Immune Effective Score as a Predictor of Response to Neoadjuvant Trastuzumab Therapy and a Prognostic Indicator for HER2-Positive Breast Cancer.

Background

Methods

Results

Conclusion

Publications

Immune Effective Score as a Predictor of Response to Neoadjuvant Trastuzumab Therapy and a Prognostic Indicator for HER2-Positive Breast Cancer.

Similar Datasets

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