Molecular Pathway Activation Markers Predicting Efficacy of Trastuzumab Therapy for HER2-positive Breast Cancer

Study Overview
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Brief Summary
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The purpose of the study is to identify molecular markers at the level of molecular pathway activation to predict efficacy of anti-HER2 therapy with Trastuzumab.

Detailed Description
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Biopsy and/or surgical samples from Her2-positive breast cancer patients treated with Trastuzumab alone or in combinations with other regimens of chemotherapy with known clinical outcomes will be collected and subjected to mRNA sequencing. Expression profiles will be analysed using original bioinformatic platform Oncobox. Based on comparison of molecular pathways activation strength and clinical response to Trastuzumab and chemotherapy, this study aims to identify molecular markers predicting efficacy of therapy with Trastuzumab and the possibility of further relapse.

Official Title
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Molecular Pathway Activation Markers Predicting Efficacy of Trastuzumab Therapy for HER2-positive Breast Cancer

Conditions
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HER2-positive Breast Cancer

Intervention / Treatment
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* Other: RNA sequencing
* Other: Transcriptome analysis
* Drug: Trastuzumab
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult females histologically confirmed HER2-positive breast cancer available FFPE samples of breast cancer tissue patients treated with Trastuzumab alone or in combination(s) with other regimens of chemotherapy with known outcome according to RECIST 1.1 stage II or more patients who have signed an informed consent Exclusion Criteria: less than 70% of intact tumor cells in available FFPE samples

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Trastuzumab monotherapy<br>Her2-positive breast cancer patients treated with Trastuzumab (monotherapy) | Other: RNA sequencing<br>* Next Generation Sequencing of RNA from tumor samples, rRNA-depleted.<br>* Other names: RNA-seq;Other: Transcriptome analysis<br>* Analysis of RNA-seq data using the Oncobox algorithm.<br>Drug: Trastuzumab<br>* Standard Trastuzumab treatment regimen recommended for breast cancer<br>|
| Chemotherapy plus Trastuzumab<br>Her2-positive breast cancer patients treated with Trastuzumab in combination with other regimens of chemotherapy | Other: RNA sequencing<br>* Next Generation Sequencing of RNA from tumor samples, rRNA-depleted.<br>* Other names: RNA-seq;Other: Transcriptome analysis<br>* Analysis of RNA-seq data using the Oncobox algorithm.<br>Drug: Trastuzumab<br>* Standard Trastuzumab treatment regimen recommended for breast cancer<br>Drug: Chemotherapy<br>* Standard chemotherapy regimen recommended for breast cancer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response by RECIST v1.1 or pathological response according to Chevallier system | Tumor response by RECIST v1.1 or pathological response according to Chevallier system | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, epidermal growth factor receptor, HER2, EGFR, biomarkers, targeted therapy, NGS, RNAseq, mRNA, transcriptome analysis, signaling pathway, intracellular molecular pathway, Oncobox, trastuzumab