To Evaluate the Characteristics of a Breast Cancer

Study Overview
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Brief Summary
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The purpose of this pilot study is to determine the prevalence of markers of chronic and cycling hypoxia and reactive species stress (oxidative and nitrosative) in the breast cancer tumor microenvironment. The study is based around four cornerstone features of the pathologic microenvironment - Hypoxia, Reactive Species (reactive oxygen and nitrogen species), HIF-1 and VEGF, which we term the HRHV axis. Fifty breast cancer patients with planned surgical excision will be administered the hypoxia marker drug, EF5, 24-36 hr prior to surgical excision. EF5 is a non-therapeutic drug and provides no direct benefit to those patients enrolled in this pilot study. Tissues obtained intra-operatively will be snap frozen and subsequently analyzed for EF5 binding. Immunohistochemical analysis of a cohort of immunohistochemical and urine markers that depict the HRHV axis will be examined. The association of the markers with the presence of hypoxia, as determined by EF5 positivity, will be determined. Data from this pilot study will be used to establish the prevalence of markers of the HRHV axis in breast cancer. This information will be crucial for future human trials in which the HRHV axis is therapeutically targeted.

Official Title
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Pilot Study to Characterize the HRHV Axis in the Microenvironment of Breast Cancers

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: EF5
* Procedure: Partial or Total Mastectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed Stage 0 - III invasive carcinoma of the breast Tumor size greater than 1-cm by radiological (mammogram/ultrasound or MRI) evaluation KPS status ≥ 70 Bilirubin ≤ 1.5x normal Creatinine ≤ 1.8 WBC > 3000/mm^3 and platelets > 100,000/mm^3 Exclusion Criteria: Pregnant or breast-feeding women Neoadjuvant chemo or hormonal therapy for existent breast malignancy Allergy to IV contrast dye History of grade III or IV peripheral neuropathy as defined by the NCI CTC Previous history of any malignancy treated with radiotherapy and/or chemohormonal therapy

Ages Eligible for Study
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Minimum Age: 18 Years

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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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All Patients<br>Single arm study analyzing tumor hypoxia after EF5 injection | Drug: EF5<br>* An infusion of EF5, a fluorinated 2-nitroimidazole, will be administered using the recommended dose of 21mg/kg one day prior to surgical procedure.<br>Procedure: Partial or Total Mastectomy<br>* A small tissue sample will be removed from the excised tissue and will be stored for later analysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate tumor characteristics |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intra and Interpatient correlations with tumor hypoxia |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, ductal breast carcinoma in situ, breast cancer in situ, invasive carcinoma, invasive ductal carcinoma, invasive lobular carcinoma