CharactHer. ICORG 12-09, V3

Study Overview
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Brief Summary
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Primary Objective: The primary aim of the study is: 1.To identify and validate a panel of molecular and cytogenetic biomarkers able to predict Durable Complete Response (DCR) after chemotherapy and trastuzumab in patients with HER2-positive locally advanced or metastatic breast cancer. Secondary Objective: The secondary aims of the study are: To perform a comprehensive exploration of the molecular and cytogenetic characteristics of DCR patients to identify any possible correlation between the tumour's biological and cytogenetic characteristics and the degree of clinical response to trastuzumab; To produce data in preparation for further translational studies on HER2-positive breast cancer.

Detailed Description
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Type of Study: Translational This is a pilot retrospective laboratory-based cohort study. Eligible patients will be identified at each one of the participating institutions by a systematic cross-matching of the datasets of Medical Oncology, Pathology and Pharmacy Departments. Patient Population: Cohort 1: TNM stage II-IV breast cancer patients with highly trastuzumab-sensitive tumours. Cohort 2: (Control group) TNM stage II-IV breast cancer patients with trastuzumab-refractory disease.

Official Title
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CharactHer: A Study of the Molecular and Cytogenetic Characteristics of HER2-positive Breast Cancers to Predict Durable Complete Response After Chemotherapy and Trastuzumab

Conditions
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HER2-positive Breast Cancer, TNM Stage II-IV Breast Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion criteria for Cohort 1: Histologically proven AJCC TNM stage II-IV invasive breast cancer HER2-positivity defined as score 3+ on IHC and/or with HER2/neu amplification on FISH test (HER2/CEP17 ratio >2.0 on PathVysion test) Evidence of complete response (CR) according to RECIST 1.1 criteria lasting for at least 36 months (for stage IV patients only) following a first-line chemotherapy and trastuzumab Pathological Complete Response (pCR) following a neo-adjuvant chemotherapy (CT) and trastuzumab (for stage II-III patients only). pCR is defined as no evidence of residual invasive carcinoma in the breast (ductal carcinoma in situ (DCIS) is allowed) AND in all the examined lymph nodes (micro-metastases and isolated tumour cells are not allowed). At least one FFPE archived tissue sample from the primary tumour and/or a metastatic site(s) available for laboratory analyses Adequate follow up information Inclusion criteria for Cohort 2: Histologically proven AJCC TNM stage II-IV invasive breast cancer HER2-positivity defined as score 3+ on IHC and/or with HER2/neu amplification on FISH test (HER2/CEP17 ratio>2.0 on PathVysion test) Progression of disease according to RECIST 1.1 while receiving trastuzumab (in association with chemotherapy or as single agent as maintenance therapy) or within 6 months from last dose of trastuzumab (for stage IV patients only) Residual invasive tumour in the breast larger than 2cm and /or at least one micro- or macro-metastasis in the axillary lymph nodes following pre-operative trastuzumab-containing chemotherapy (for stage II-III patients only) At least one FFPE archived tissue sample from the primary tumour and/or a metastatic site(s) available for laboratory analyses Adequate follow up information Exclusion Criteria: 1. Any deviation from the above mentioned Inclusion criteria
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1<br>TNM stage II-IV breast cancer patients with highly trastuzumab-sensitive tumours. | |
| Cohort 2(Control Group)<br>TNM stage II-IV breast cancer patients with trastuzumab-refractory disease. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Panel of molecular and cytogenetic biomarkers able to predict Durable Complete Response (DCR) after chemotherapy and trastuzumab in patients with HER2-positive locally advanced or metastatic breast cancer. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2-positive breast cancer, durable complete response, cytogenetic characteristics, molecular characteristics, trastuzumab