Inclusion Criteria:

   - Histologically-proven metastatic or locally-advanced relapsed/refractory HER2+ breast
   cancer based on the most recently available tumor biopsy collected from the patient.
   Tumors may be estrogen receptor (ER)/progesterone receptor (PgR) positive or negative.

   - Have received at least 2 prior lines of anti-HER2 directed therapy in the metastatic
   setting, or in case of having received (neo)adjuvant pertuzumab, at least 1 prior line
   of anti-HER2 directed therapy in the metastatic setting. In either case, patients must
   have received prior treatment with pertuzumab, in the (neo)adjuvant or metastatic
   setting. Prior radiotherapy, hormonal therapies, and other anti-HER2 therapies are
   allowed.

   - Prior treatment with at least one, and no more than three, lines of therapy overall in
   the metastatic setting. Patients must have progressed on or following, the most recent
   line of therapy.

   - Resolution of all chemotherapy or radiation-related toxicities to ≤ Grade 1

   - Life expectancy ≥ 12 weeks

   - Acceptable laboratory parameters

   - Women of childbearing potential must have negative pregnancy test performed within 14
   days of randomization and on the first day of treatment. All subjects must agree to
   use an effective form of contraception for the duration of study treatment and for 7
   months after the last dose of study drug.

Infusion sub-study prior therapy requirements: Same as above, except:

   - Must have received 4 or more prior lines or therapy in the metastatic setting

   - Must have received prior trastuzumab, pertuzumab, and T-DM1

Exclusion Criteria:

   - Known, untreated brain metastasis. Patients with signs or symptoms of brain metastasis
   must have a CT or MRI performed within 4 weeks prior to randomization to specifically
   exclude the presence of radiographically-detected brain metastases

   - History of uncontrolled seizures within 6 months of randomization

   - History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation

   - History of clinically significant cardiovascular disease

   - Clinically-significant pulmonary compromise, including a requirement for supplemental
   oxygen use to maintain adequate oxygenation

   - Any condition that would be a contraindication to receiving trastuzumab as described
   in the approved local label or a condition that would prevent treatment with the
   physician's choice of chemotherapy