RATIONALE: Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving letrozole before surgery allows us to monitor the effects of letrozole on the tumor on a molecular level and determine markers of response to treatment. PURPOSE: This study will show us how well letrozole works in treating postmenopausal women with stage I, II or III breast cancer that can be removed by surgery.
OBJECTIVES: Primary To determine that in breast tumors that continue to exhibit high proliferation (i.e., Ki67) upon hormone deprivation (with letrozole), their gene expression and/or a mutational or proteomic signatures will harbor molecules or 'pathways' that are biomarkers of resistance to endocrine therapy or a cause of it. The ultimate goal of these aims is to identify clinically-targetable pathways which can be exploited to enhance responses and survival in patients with ER+ breast cancer. OUTLINE: Patients receive oral letrozole once daily for 7-21 days in the absence of disease progression or unacceptable toxicity. Within 24 hours after the last dose of letrozole, patients undergo total mastectomy or segmental resection with lymph node evaluation. Pre-treatment diagnostic breast tissue is obtained. Patients undergo treatment and then undergo standard of care mastectomy or lumpectomy. Pre and post treatment tumor tissue samples are analyzed for Ki67, P-ER, ER, progesterone receptor (PR), and caspase 3 by immunohistochemistry; and RNA microarray.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
213
Take by mouth at a dose of 2.5 mg on days 7-21
Blood used for gene expression analysis and reverse transcriptase-polymerase chain reaction
Tissue collection,Surgery to remove tumor, Tumor tissues used for laboratory biomarker analysis
Emory University
Atlanta, Georgia, United States
Surgical Associates, Inc.
Tulsa, Oklahoma, United States
Allegheny Cancer Center
Pittsburgh, Pennsylvania, United States
Vanderbilt-Ingram Cancer Center, One Hundred Oaks
Nashville, Tennessee, United States
Ki67 index measured in hormone receptor-positive breast cancers compared to those that are hormone receptor-negative
Ki67 index is measured by counting the percentage of cells staining for Ki67 in a section of breast tissue. The number of stained cells will be compared in tissue that is hormone receptor-positive tissue to tissue that is hormone receptor negative.
Time frame: day 7 to day 21
In situ apoptotic effect of letrozole
Measured by level of capase-3 in post-treatment breast tissue.
Time frame: day 7 to day 21
Identification of a recurrence risk biomarker profile using RNA microarray
RNA will be extracted from pre- and post-treatment breast tissue and will be compared with the Ki67 index
Time frame: day 7 to day 21
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Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States