Molecular Mechanisms of Clinical Resistance to Targeted Therapy Among Patients With Breast Cancer

Inclusion Criteria:

All patients:

- Diagnosed with progressive, recurrent or metastatic HER2+ or ER+ breast cancer.

Cohort 1

- 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 or recurrence after prior therapy (e.g. radiologic
progression by RECIST criteria or new metastasis).

- Prior tumor biopsy (may be original) defined as HER2+ by amplification by FISH (>1.9
gene copy number) or IHC 3+.

Cohort 2

- Patients who previously received treatment with hormonal therapy (including tamoxifen,
toremifene, raloxifene, anastrozole, letrozole, exemestane, fulvestrant, ARN-810) as a
part of adjuvant therapy and now have progressive or recurrent breast cancer or
patients who previously (or currently) receive hormonal therapy as part of a regimen
for metastatic breast cancer and subsequently experienced evidence of disease
progression.

Cohort 3

- Patients not eligible for Cohorts 1 or 2, but previously received treatment of any
other kind for breast cancer.

Exclusion Criteria:

- Patients who are unable to consent to a biopsy.

- Patients for whom a repeat biopsy would be medically unsafe