Molecular Mechanisms of Clinical Resistance to Anti-HER2 Therapy Among Patients With HER2 Amplified Breast Cancer

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