Lapatinib Resistance in Patients With Breast Cancer

Case Comprehensive Cancer Center

Overview

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.

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.

Study Type

OBSERVATIONAL

Conditions

Breast Cancer

Interventions

lapatinib ditosylateDRUG

fluorescence in situ hybridizationGENETIC

gene expression analysisGENETIC

mutation analysisGENETIC

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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

Locations (9)

Geauga Regional Hospital

Cleveland, Ohio, United States

Lake/University Ireland Cancer Center

Cleveland, Ohio, United States

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Outcomes

Primary Outcomes

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

Data from ClinicalTrials.gov

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