Duct Endoscopy in Assessing Cellular Atypia in the Breast Duct Fluid of Women With a Genetic Risk for Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Diagnostic procedures, such as breast duct endoscopy, may improve the ability to detect breast cancer earlier and plan more effective treatment. PURPOSE: This phase II trial is studying how well breast duct endoscopy works in assessing cellular atypia (abnormal cells) in the breast ducts of women with a genetic risk for breast cancer.

Detailed Description
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OBJECTIVES: Primary Correlate cell yield and morphology findings from ductal lavage with duct endoscopy findings and any subsequent surgical pathology findings in high-risk women with BRCA1, BRCA2, or p53 gene mutations who have cellular atypia. Determine the prevalence of occult breast cancer in patients with cellular atypia undergoing duct endoscopy. Secondary Determine patient acceptance of duct endoscopy. Perform immunohistochemical analysis (including estrogen receptor, progesterone receptor, HER2-neu receptor, epidermal growth factor receptor, p53, and proliferation marker expression) for markers potentially associated with breast cancer in these patients. Determine potential molecular markers of malignancy by gene methylation, gene expression, and proteomics in these patients. OUTLINE: Patients undergo nipple aspiration to identify productive ducts and collect fluid for tumor marker assessment followed by ductal lavage over 15 minutes. Patients undergo duct endoscopy over approximately 30 minutes under local anesthesia. If no abnormality is found, duct endoscopy is repeated in 6 months. If the repeat duct endoscopy is normal, patients continue to undergo nipple aspiration or ductal lavage as specified in protocols RMNHS-2242 and RMNHS-2269. If an abnormality is found during either the initial or repeat duct endoscopy, patients may undergo further assessment comprising imaging or biopsy and/or appropriate surgical intervention. Fluid is analyzed for tumor markers by immunohistochemistry. Candidate genes are analyzed by gene methylation studies, gene expression arrays, and proteomic analysis. Patients are followed for at least 5 years. PROJECTED ACCRUAL: A total of 45-60 patients will be accrued for this study within 2 years.

Official Title
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Evaluation of the Role of Duct Endoscopy in the Assessment of Cellular Atypia Within Breast Duct Fluid in High-Risk Women Carrying BRCA1/2 or p53 Gene Mutations

Conditions
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Breast Cancer

Intervention / Treatment
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* Genetic: cytogenetic analysis
* Genetic: proteomic profiling
* Other: cytology specimen collection procedure
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Procedure: breast duct lavage


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of cellular atypia in nipple aspirate or ductal lavage fluid Enrollment on RMNHS-2242 or RMNHS-2269 required No inflammatory breast cancer Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 18 to 64 Sex Female Menopausal Status Any status Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Other No prior allergy to eutectic mixture of local anesthetics (EMLA®) cream or lidocaine No severe illness that would preclude study participation No mental illness or handicap that would preclude study compliance No active infection or inflammation in the breast being studied No nursing within the past 12 months Not pregnant Not unconscious PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy Not specified Endocrine therapy No prior tamoxifen Radiotherapy Not specified Surgery No prior subareolar surgery (e.g., papilloma resections, biopsies, or fine needle aspirations) or any other surgery that may disrupt the ductal systems within 2 cm of the nipple Biopsies and fine needle aspirations > 2 cm from the nipple are allowed No prior breast implantation on proposed lavage side Other No prior chemopreventative agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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Female

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Genetic: cytogenetic analysis|nan|
|Genetic: proteomic profiling|nan|
|Other: cytology specimen collection procedure|nan|
|Other: immunohistochemistry staining method|nan|
|Other: laboratory biomarker analysis|nan|
|Procedure: breast duct lavage|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of cell yields and morphology from ductal lavage vs the ductal anatomy visualized at duct endoscopy |  |  | 
| Prevalence of occult pathology (malignant and benign) as assessed by duct endoscopy on intraduct sampling |  |  | 
| Sensitivity and specificity of ductal lavage to duct endoscopy in detecting atypia or malignancy |  |  | 
| Comparison of cell yields vs final surgical pathology |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer