Lapatinib Resistance in Patients With Breast Cancer

Case Comprehensive Cancer Center (Case CCC)

Status: Withdrawn

Conditions: Breast Cancer

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

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT00898573

CASE15107 (Other Identifier)

CASE-15107-CC488

P30CA043703 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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