RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. PURPOSE: This phase II trial is studying how well everolimus works in treating women with breast cancer that can be removed by surgery.
OBJECTIVES: Primary * Determine whether the administration of everolimus results in a decrease of total choline, a surrogate marker of response, in at least 30% of women with resectable breast cancer. Secondary * Determine whether tumors with activated mTOR signaling, as measured by phosphorylation of 4E-BP1 and activity of cap dependent translational complex, will identify those women responsive to everolimus. OUTLINE: Patients receive oral everolimus once daily on days 1-7 in the absence of disease progression or unacceptable toxicity. Within 24 hours after completing everolimus, patients undergo surgery. Tumor tissue samples are collected at baseline and during surgery for the analysis of mTOR targets (i.e., 4E-BP1, p70S6 kinase phosphorylation), Ki67, cleaved caspase 3, and activity of cap dependent translational complex by immunohistochemical assays. Patients also undergo MRI/MRS before and after everolimus therapy for total choline and glucose levels measurement. After completion of study therapy, patients are followed for 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
5 mg/day x 7 days by mouth
Definitive excision of breast cancer tissue
University of Minnesota Children's Hospital - Fairview
Minneapolis, Minnesota, United States
Decrease of total choline in at least 30% of patients
Choline is measured by magnetic resonance imaging (MRI/MRS) scan.
Time frame: Pre-Treatment Compared to Post-Treatment (Day 7)
Identification of response to everolimus by activated mTOR signaling
Two core biopsies will be obtained at the time of diagnostic biopsy. Waste tumor tissue obtained during surgery will be collected at the time of surgery. It will be stored under liquid nitrogen until they can be examined for activation of mTOR targets, specifically, 4E-BP1, p70S6 kinase phosphorylation, and activity of cap dependent translational complex.
Time frame: Pre-Treatment Compared to Post-Surgery (Day 7)
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