DNA Analysis of Tumor Tissue Samples From Patients With Recurrent or Metastatic Breast Cancer That Expresses HER2

• Comparison of expression levels of PTEN prior to treatment with HER2-targeting agents with levels after disease progression/recurrence [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Mutations relative to known HER2 sequences [ Time Frame: 3 years ] [ Designated as safety issue: No ]

• Comparison of expression levels of MUC-4 and PTEN prior to treatment with HER2-targeting agents with levels after disease progression/recurrence [ Designated as safety issue: No ]
• Mutations relative to known HER2 sequences [ Designated as safety issue: No ]

• Mutations in the PIK3CA, and PTEN genes [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Comparison of genome-wide expression changes in patients with disease progression after HER2-targeting agents with characteristic profiles of HER2-positive breast cancer [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Shed HER2 extracellular domain in tumors samples obtained after disease progression/recurrence [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• To evaluate dynamic proteomic changes in response to inhibition of the RTK/PI3K/ATK/mTOR pathway [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• To look for mutations in other druggable oncogenic pathways in tumors progressing on anti-HER2 therapy [ Time Frame: 3 years ] [ Designated as safety issue: No ]

• Mutations in the PIK3Ca, PTEN, and epidermal growth factor receptor genes [ Designated as safety issue: No ]
• Comparison of genome-wide expression changes in patients with disease progression after HER2-targeting agents with characteristic profiles of HER2-positive breast cancer [ Designated as safety issue: No ]
• HER2 amplification as measured by a novel oligonucleotide microarray-based analysis [ Designated as safety issue: No ]
• Shed HER2 extracellular domain in tumors samples obtained after disease progression/recurrence [ Designated as safety issue: No ]

RATIONALE: Studying samples of tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients respond to treatment.

PURPOSE: This laboratory study is looking at tissue samples from patients with recurrent or metastatic breast cancer that expresses HER2.

Patients diagnosed with progressive, recurrent or metastatic HER2+ breast cancer.

• Genetic: comparative genomic hybridization
• Genetic: fluorescence in situ hybridization
• Genetic: microarray analysis
• Genetic: mutation analysis
• Genetic: reverse transcriptase-polymerase chain reaction
• Other: diagnostic laboratory biomarker analysis
• Other: immunoenzyme technique
• Other: immunohistochemistry staining method
• Procedure: biopsy
• Procedure: histopathologic examination

Inclusion Criteria:

• Patients diagnosed with progressive, recurrent or metastatic HER2+ breast cancer and who fulfill the following eligibility criteria will be considered eligible for this study.
• Patients who previously received treatment with anti-HER2 therapy (including trastuzumab, pertuzumab, TDM1, or lapatinib) as part of adjuvant chemotherapy and now have progressive or recurrent breast cancer, or patients who previously (or currently) received anti-HER2 therapy as part of a regimen for metastatic breast cancer and subsequently experienced evidence of disease progression (e.g. radiologic progression by WHO criteria or new metastasis).
• Patients with a prior tumor biopsy (may be original) defined as HER2+ by amplification by FISH (>1.9 gene copy number) or IHC 3+.

For the purposes of establishing baselines in some of the assays, separate from the above inclusion criteria, a cohort of patients diagnosed with any recurrent breast cancer will be eligible under the following criteria:

• Previously received treatment of any kind for breast cancer and now have recurrent breast cancer.

Exclusion Criteria:

• Patients who are unable to consent to a biopsy.
• Patients for whom a repeat biopsy would be medically unsafe