FLT PET in Measuring Treatment Response in Patients With Newly Diagnosed Estrogen Receptor-Positive, HER2-Negative Stage I-III Breast Cancer

Study Overview
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Brief Summary
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This clinical trial studies fluorine F 18 fluorothymidine (FLT) positron emission tomography (PET) in measuring treatment response in patients with newly diagnosed estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage I-III breast cancer. Comparing results of diagnostic procedures done before and during hormone therapy may help doctors predict a patient's response to treatment and help plan the best treatment.

Detailed Description
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PRIMARY OBJECTIVES: I. Measure the effect of a short course of endocrine therapy on primary breast cancer metabolism and proliferation by measuring changes in serial FLT PET measures pre and post a short course of endocrine therapy. SECONDARY OBJECTIVES: I. Compare changes in imaging measures to tissue measures of response, in particular antigen identified by proliferation-related Ki-67 antigen (Ki-67), in the pre-therapy biopsy versus the post-therapy surgical specimen. II. Correlate imaging measures to measures of gene expression from pre and post therapy assays to determine if there are molecular changes associated with early response to therapy. OUTLINE: Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment.

Official Title
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Imaging Early Response of ER+, HER2- Breast Cancer to Aromatase Inhibitor (AI) +/- Ovarian Suppression (OS) Therapy With [18F]Fluorothymidine (FLT) PET

Conditions
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Estrogen Receptor Positive, HER2/Neu Negative, Male Breast Carcinoma, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer, Stage IIIA Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer

Intervention / Treatment
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* Drug: Fluorothymidine F-18
* Procedure: Positron Emission Tomography
* Other: Laboratory Biomarker Analysis
* Drug: Run-in (short pre-surgery course) of endocrine-targeted therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A new diagnosis of invasive breast cancer > 1.0 cm in size, ER+ clinical stage I-III Patient must have surgical resection followed by systemic adjuvant therapy with an aromatase inhibitor (AIs) as part of planned treatment; any approved AI at standard clinical dosing may be used; in pre-menopausal patients, ovarian suppression with a gonadotropin-releasing hormone (GnRH) agonist will be started prior to initiation of the AI on a separate clinical trial in parallel with the imaging study Have tissue block available from core biopsy for correlative biomarkers and genomic assay Have menopausal status determined prior to study enrollment; for study purposes, postmenopausal is defined as A prior documented bilateral oophorectomy, or A history of at least 12 months without spontaneous menstrual bleeding, or Age 60 or older with a prior hysterectomy without oophorectomy, or Age less than 60 with a prior hysterectomy without oophorectomy (or in whom the status of the ovaries is unknown) with a documented follicle-stimulating hormone (FSH) level demonstrating confirmatory elevation in the postmenopausal range for the lab Negative pregnancy test within 7 days of baseline positron emission tomography (PET) scan for pre-menopausal patients Tumor HER2/neu expression must be determined (as part of standard clinical care) prior to study enrollment; HER2 may be tested by any Food and Drug Administration (FDA) approved HER2 testing method; if determination is intermediate by immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) or another alternate HER2 test must be performed Be a candidate for [18F]FLT PET imaging Be informed of the investigational nature of this study and provide written informed consent in accordance with institutional and federal guidelines prior to study-specific screening procedures Be willing and able to comply with scheduled visits and other trial procedures Exclusion Criteria: Current use of aromatase inhibitor as prevention or treatment for breast cancer Life expectancy of less than two months HER2/neu positive by IHC and/or another FDA approved HER2 testing method Inability to tolerate scanning (e.g. - claustrophobia, severe pain) Weight exceeding capacity of imaging table

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Diagnostic (FLT PET)<br>Patients undergo FLT PET at baseline and 1-6 weeks after the start of treatment. | Drug: Fluorothymidine F-18<br>* Undergo FLT PET<br>* Other names: 3'-deoxy-3'-[18F]fluorothymidine;Procedure: Positron Emission Tomography<br>* Undergo FLT PET<br>* Other names: Positron Emission Tomography Scan;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Run-in (short pre-surgery course) of endocrine-targeted therapy<br>* Patients undergo run-in (short pre-surgery course) of endocrine-targeted therapy with aromatase inhibitor between the two (baseline and repeat) FLT PET scans. This is not an experimental therapy. This is a standard of care therapy that patients will continue after surgery, when the study is completed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Net Influx Constant (Ki) by FLT PET | Percent change between pre-treatment (baseline) and post-therapy PET measurements in breast tumors will be computed. Association between Ki-67 and Ki by FLT (KFLT) decline will be analyzed using the mid-P adjustment to Fisher's exact test to evaluate the potential clinical utility of change in FLT as a biomarker for early response, using Ki-67 as the standard for early response. | Baseline to up to 6 weeks | 
| Percent Change in SUV by FLT PET | Percent change between pre-treatment (baseline) and post-therapy measurements of FLT standardized uptake value (SUV) in breast tumors will be computed. | Baseline to up to 6 weeks | 
| Percentage of Ki-67 Positive Tumor Cells in Surgical (Post-therapy) Sample | Surgically removed breast tumor tissue is stained using immuno-histochemistry techniques to visualize dividing cells expressing the Ki-67 protein, which is a cellular marker for proliferation. | 1 to 6 weeks post-therapy start | 
| Percentage Change in Ki-67 Positive Cells Between Pre-therapy and Post-therapy Tumor Specimens | Tumor tissue samples from pre-treatment (baseline) biopsy and post-treatment surgery are stained using immuno-histochemistry techniques to visualize dividing cells expressing the Ki-67 protein, which is a cellular marker for proliferation. The % values of positive cells from the baseline and post-treatment samples are then compared for each individual patient. Association between Ki-67 and KFLT decline will be analyzed to evaluate the potential clinical utility of change in FLT as a biomarker for early response, using Ki-67 as the standard for early response. | Baseline to up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in K1 (Blood Flow Parameter) by FLT PET | Percent change between pre-treatment (baseline) and post-therapy PET measurements in breast tumors will be computed. | Baseline to up to 6 weeks | 
| Baseline Ki (Flux Constant) Values by FLT PET | Ki (flux constant) in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET scan | Baseline | 
| Baseline FLT Transport (K1) Values by FLT PET | K1 (blood flow measure) in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET | Baseline | 
| Baseline Standardized Uptake Values (SUV) by FLT PET | FLT SUV in breast tumor tissue as determined by the pre-therapy (baseline) FLT PET | Baseline | 
| Post-therapy Ki (Flux Constant) Values by FLT PET | Ki (flux constant) in breast tumor tissue as determined by the post-therapy FLT PET | 1 to 6 weeks post-therapy start | 
| Post-treatment FLT Transport (K1) Values by FLT PET | K1 (blood flow measure) in breast tumor tissue as determined by the post-therapy FLT PET | 1 to 6 weeks post-therapy start | 
| Post-treatment Standardized Uptake Values (SUV) by FLT PET | FLT SUV in breast tumor tissue as determined by the post-treatment FLT PET | 1 to 6 weeks post-therapy start |