Doxorubicin Hydrochloride Liposome in Treating Women With Ductal Carcinoma in Situ Undergoing Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. PURPOSE: This clinical trial is studying the side effects of doxorubicin hydrochloride liposome and to see how well it works in treating women with ductal carcinoma in situ undergoing surgery.

Detailed Description
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OBJECTIVES: To demonstrate the efficacy and safety of neoadjuvant intraductal pegylated liposomal doxorubicin hydrochloride in women with ductal breast carcinoma in situ undergoing surgery. To demonstrate the ability to identify and cannulate the duct demonstrating precancerous disease in these women. To integrate the Humboldt Community Breast Health Project into the planning and execution of this study. OUTLINE: Patients undergo identification of the intraductal lesions via cannulization. Patients receive pegylated liposomal doxorubicin hydrochloride (PLD) intraductally through the inserted cannula. Some patients are randomized to receive saline instead of PLD. Within 4-6 weeks, all patients undergo surgery. Patients undergo tissue and ductal fluid sample collection at baseline and at surgery for correlative laboratory studies. Tissue samples are assessed for histomorphology, proliferation (Ki67), cell death (apoptosis index), genetic markers, necrosis, inflammation, and loss of heterozygosity by HE stain, IHC, TUNEL, and PCR. Nipple aspirate and ductal lavage fluid samples are analyzed for cytomorphology (cellular atypia), proliferation (Ki67), cell death (TUNEL), differentiation (G-actin), and genetic markers (FISH) by quantitative fluorescence image analysis. Samples are also analyzed for bFGF and CEA by ELISA, and methylation by PCR. After completion of study therapy, patients are followed every 6 months for at least 2 years.

Official Title
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Intraductal Therapy of DCIS: A Presurgery Study

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: pegylated liposomal doxorubicin hydrochloride
* Genetic: DNA methylation analysis
* Genetic: TdT-mediated dUTP nick end labeling assay
* Genetic: fluorescence in situ hybridization
* Genetic: loss of heterozygosity analysis
* Genetic: polymerase chain reaction
* Other: immunoenzyme technique
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Procedure: breast duct lavage
* Procedure: neoadjuvant therapy
* Procedure: therapeutic conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of ductal breast carcinoma in situ by core needle biopsy No pathological invasive or microinvasive disease in the affected breast Mammographic microcalcifications are limited to one ductal system or one quadrant of breast Hormone receptor status not specified PATIENT CHARACTERISTICS: Menopausal status not specified Must be able to undergo necessary surgery Not pregnant PRIOR CONCURRENT THERAPY: No prior surgery or radiotherapy to the recently diagnosed breast More than 12 months since prior chemotherapy No prior subareolar breast surgery to the affected breast Not concurrently involved in a research protocol for unapproved new drug evaluation

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Masking: Single


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: pegylated liposomal doxorubicin hydrochloride|nan|
|Genetic: DNA methylation analysis|nan|
|Genetic: TdT-mediated dUTP nick end labeling assay|nan|
|Genetic: fluorescence in situ hybridization|nan|
|Genetic: loss of heterozygosity analysis|nan|
|Genetic: polymerase chain reaction|nan|
|Other: immunoenzyme technique|nan|
|Other: immunohistochemistry staining method|nan|
|Other: laboratory biomarker analysis|nan|
|Procedure: breast duct lavage|nan|
|Procedure: neoadjuvant therapy|nan|
|Procedure: therapeutic conventional surgery|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy |  |  | 
| Safety |  |  | 
| Ability to identify and cannulate the duct |  |  | 
| Integration of the Humboldt Community Breast Health Project into the planning and execution of this study |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ductal breast carcinoma in situ