A Phase III Randomized, Multicenter, Two-Arm, Open-Label Trial to Evaluate the Efficacy of Trastuzumab Emtansine Compared With Treatment of Physician's Choice in Patients With HER2 Positive Metastatic Breast Cancer Who Have Received at Least Two Prior Regimens of HER2 Directed Therapy

Inclusion Criteria:

- Adult patients, >/= 18 years of age

- Histologically or cytologically documented breast cancer

- Metastatic or unresectable locally advanced/recurrent breast cancer

- HER2-positive disease by prospective laboratory confirmation

- Disease progression on the last regimen received as defined by the investigator

- Prior treatment with an trastuzumab, a taxane, and lapatinib

- Disease progression after at least two regimens of HER2-directed therapy in the
metastatic or unresectable locally advanced/recurrent setting

- Adequate organ function, as evidenced by laboratory results

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- LVEF >/= 50% by ECHO or MUGA

Exclusion Criteria:

- Chemotherapy
- Trastuzumab
- Lapatinib
- Prior enrolment in a T-DM1 containing study, regardless whether the patient received
prior T-DM1

- Brain metastases that are untreated or symptomatic, or require any radiation, surgery
or corticosteroid therapy to control symptoms within 1 month of randomization