Dataset Information

Clinical application of multiple reaction monitoring-mass spectrometry to HER2 measurements as a potential diagnostic tool for breast cancer therapy

ABSTRACT: Although the determination of HER2 expression in breast cancer would be of critical importance in the clinical management related to the selection of the patients who are expected to benefit from trastuzumab therapy, the conventional techniques have inherent limitations that disqualify their use as gold standards. Specifically, fluorescence in situ hybridization (FISH), which is mandatory for determining IHC 2+ cases, is time-consuming and economically inefficient. To address this shortcoming, we aimed to discriminate the equivocal HER2 status, which cannot be classified by the conventional method such as IHC, using a highly sensitive and quantitative MRM-MS assay. In order to assess the agreement between MRM-MS and IHC/FISH data, the quantitative data of a HER2 peptide was normalized by junctional adhesion molecule A (JAM1) levels, which is an epithelial cell-specific protein. The normalized HER2 levels differentiated the ambiguous IHC results of. In addition, the MRM-MS data distinguished HER2-negative breast cancer from the HER2-positive breast cancer that was expected to benefit from trastuzumab therapy. The newly developed HER2-targeted proteomic assay may provide a general strategy for complementing the limitations of conventional HER2-targeted therapeutic strategies.

ORGANISM(S): Homo Sapiens

SUBMITTER: Hyunsoo Kim

PROVIDER: PXD017691 | panorama | Wed Mar 03 00:00:00 GMT 2021

REPOSITORIES: PanoramaPublic

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Publications

Clinical Application of Multiple Reaction Monitoring-Mass Spectrometry to Human Epidermal Growth Factor Receptor 2 Measurements as a Potential Diagnostic Tool for Breast Cancer Therapy.

Do Misol M Kim Hyunsoo H Yeo Injoon I Lee Jihyeon J Park In Ae IA Ryu Han Suk HS Kim Youngsoo Y

Clinical chemistry 20201001 10

<h4>Background</h4>Human epidermal growth factor receptor 2 (HER2) is often overexpressed in breast cancer and correlates with a worse prognosis. Thus, the accurate detection of HER2 is crucial for providing the appropriate measures for patients. However, the current techniques used to detect HER2 status, immunohistochemistry and fluorescence in situ hybridization (FISH), have limitations. Specifically, FISH, which is mandatory for arbitrating 2+ cases, is time-consuming and costly. To address t ...[more]

PMID: 33001186

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Project description:Gene expression data of HER2+ breast tumor samples Increasing evidence indicates that a subset of patients with HER2-positive breast cancer may achieve significant clinical benefit with anti-HER2 targeted therapy without chemotherapy. Thus, identification of biomarkers of long-term benefit from anti-HER2 agents is needed, especially in the metastatic setting. In the HERLAP study (NCT00842998), patients with HER2-positive metastatic breast cancer were randomized to trastuzumab or lapatinib as first-line therapy. Patients showing radiological signs of tumor regression after 8 weeks of treatment were allowed to continue on single agent anti-HER2 therapy until disease progression. Chemotherapy was added to anti-HER-2 therapy in patients failing to achieve tumor regression at the 8-week evaluation and those progressing at any time. Expression analysis of 105 selected genes was performed from formalin-fixed paraffin-embedded in 17 primary tumor samples. The research-based PAM50 intrinsic subtypes were also identified. The association of the expression of each biomarker with clinical outcome endpoints was evaluated. Nineteen patients were enrolled. In 4 patients (21.1%) we observed disease control lasting longer than 12 months with single agent anti-HER2 therapy (range 14.9-38.8 months). High expression of 17q12-21 amplicon genes HER2 and GRB7, and the PAM50 HER2-enriched intrinsic profile, were found significantly associated with 8-week overall response rate and with the duration of disease control during single agent anti-HER2 therapy. Conversely, high expression of luminal-related genes such as PGR, MDM2 or PIK3CA, or the PAM50 luminal intrinsic profile, was found associated with reduced benefit from single agent anti-HER2 therapy. Conclusions: Our data indicate that gene expression-based biomarkers can identify patients with HER2-positive metastatic breast cancer that benefit substantially from single agent chemo-free anti-HER2 targeted therapy. In the study presented here, a well-defined cohort of 21 breast cancer cases from the HERLAP trial, was used to acquire expression profiles of a total of 105 unique genes

Dataset Information

Clinical application of multiple reaction monitoring-mass spectrometry to HER2 measurements as a potential diagnostic tool for breast cancer therapy

Publications

Clinical Application of Multiple Reaction Monitoring-Mass Spectrometry to Human Epidermal Growth Factor Receptor 2 Measurements as a Potential Diagnostic Tool for Breast Cancer Therapy.

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