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.

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