Breast Cancer
Conditions
Keywords
breast cancer, ductal breast carcinoma in situ, breast cancer in situ, invasive carcinoma, invasive ductal carcinoma, invasive lobular carcinoma
Brief summary
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.
Interventions
DRUGEF5
An infusion of EF5, a fluorinated 2-nitroimidazole, will be administered using the recommended dose of 21mg/kg one day prior to surgical procedure.
PROCEDUREPartial or Total Mastectomy
A small tissue sample will be removed from the excised tissue and will be stored for later analysis.
Sponsors
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Mark Dewhirst
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate tumor characteristics | 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Intra and Interpatient correlations with tumor hypoxia | 3 years |
Countries
United States
Outcome results
None listed