Letrozole in Treating Postmenopausal Women With Stage I, II or III Breast Cancer That Can Be Removed by Surgery
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.
|Breast Cancer||Drug: letrozole Other: Blood Collection Procedure: biopsy/lumpectomy/mastectomy|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Pre-Surgical Trial of Letrozole in Post-Menopausal Patients With Operable Hormone-Sensitive Breast Cancer (Spore)|
- Ki67 index measured in hormone receptor-positive breast cancers compared to those that are hormone receptor-negative [ Time Frame: day 7 to day 21 ]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.
- In situ apoptotic effect of letrozole [ Time Frame: day 7 to day 21 ]Measured by level of capase-3 in post-treatment breast tissue.
- Identification of a recurrence risk biomarker profile using RNA microarray [ Time Frame: day 7 to day 21 ]RNA will be extracted from pre- and post-treatment breast tissue and will be compared with the Ki67 index
|Study Start Date:||March 2008|
|Estimated Study Completion Date:||September 2019|
|Estimated Primary Completion Date:||March 2019 (Final data collection date for primary outcome measure)|
Take by mouth at a dose of 2.5 mg on days 7-21Other: Blood Collection
Blood used for gene expression analysis and reverse transcriptase-polymerase chain reactionProcedure: biopsy/lumpectomy/mastectomy
Tissue collection,Surgery to remove tumor, Tumor tissues used for laboratory biomarker analysis
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00651976
|United States, Georgia|
|Atlanta, Georgia, United States|
|United States, Oklahoma|
|Surgical Associates, Inc.|
|Tulsa, Oklahoma, United States, 74136|
|United States, Pennsylvania|
|Allegheny Cancer Center|
|Pittsburgh, Pennsylvania, United States, 15212|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center at Franklin|
|Nashville, Tennessee, United States, 37064|
|Vanderbilt-Ingram Cancer Center, One Hundred Oaks|
|Nashville, Tennessee, United States, 37204|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232-6838|
|Principal Investigator:||Ingrid Meszoely, MD||Vanderbilt-Ingram Cancer Center|