Lapatinib Resistance in Patients With Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Studying samples of tumor tissue and blood from patients with cancer in the laboratory may help doctors learn more about cancer and the development of drug resistance in patients. PURPOSE: This research study is looking at lapatinib resistance in patients with breast cancer.

Detailed Description
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OBJECTIVES: To identify secondary ErbB2 mutations in tumor tissue samples from patients with ErbB2-positive breast cancer treated with lapatinib ditosylate. To investigate ErbB2 copy number changes and expression levels. To determine abnormalities of other pathways (e.g., c-MET and PI3K) as potential mechanisms of resistance. OUTLINE: Previously collected tumor tissue samples* are obtained for genetic analysis studies. Samples are analyzed for secondary ErbB2 mutations by nested PCR; ErbB2 copy number changes by quantitative PCR and standard histological FISH; and ErbB2 expression levels by quantitative RT-PCR and IHC. Patients also undergo blood sample collection for extraction of DNA (as normal control DNA) and isolation of EpCAM-positive circulating tumor cells using immunomagnetic cell separation technology. Additional research studies may include mutational and amplification analysis of the c-MET and PI3K pathways. NOTE: *Patients may undergo biopsy if a post-treatment tumor tissue sample is unavailable.

Official Title
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Study of Resistance Mechanisms Against Lapatinib in Patients With ErbB-2-Positive Breast Cancers

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: lapatinib ditosylate
* Genetic: fluorescence in situ hybridization
* Genetic: gene expression analysis
* Genetic: mutation analysis
* Genetic: polymerase chain reaction
* Genetic: reverse transcriptase-polymerase chain reaction
* Other: cell sorting
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Pathologically confirmed invasive breast cancer ErbB2-positive disease Has received or is currently receiving lapatinib ditosylate Documented clinical benefit while receiving lapatinib ditosylate (e.g., stable disease of ≥ 12 weeks duration OR a radiographic response) Must have tumor tissue samples available for research studies Hormone receptor status not specified PATIENT CHARACTERISTICS: Menopausal status not specified Not pregnant* Coagulation profile normal* Platelet count > 100,000/mm³* NOTE: *For patients requiring a post-treatment biopsy PRIOR CONCURRENT THERAPY: See Disease Characteristics Concurrent chemotherapy or trastuzumab (Herceptin®) allowed No concurrent anticoagulants, including warfarin or low-molecular weight heparin* No concurrent antiplatelet therapy, including aspirin, clopidogrel, or other antiplatelet agents* NOTE: *For patients requiring a post-treatment biopsy
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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: lapatinib ditosylate|nan|
|Genetic: fluorescence in situ hybridization|nan|
|Genetic: gene expression analysis|nan|
|Genetic: mutation analysis|nan|
|Genetic: polymerase chain reaction|nan|
|Genetic: reverse transcriptase-polymerase chain reaction|nan|
|Other: cell sorting|nan|
|Other: immunohistochemistry staining method|nan|
|Other: laboratory biomarker analysis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary ErbB2 mutations |  |  | 
| ErbB2 copy number changes and expression levels |  |  | 
| Abnormalities of other pathways (e.g., c-MET and PI3K) as potential mechanisms of resistance |  |  | 

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