Inclusion Criteria:

          1. Histopathologically confirmed primary breast cancer with metastatic lesions.

          2. Confirmed HER2 overexpression or gene-amplified tumor

          3. At least two prior HER2-directed therapy regimens for breast cancer, including
             trastuzumab and trastuzumab emtansine (TDM-1, KADCYLA®)

          4. Patient is at least 18, and ≤90 years of age.

          5. Patient has adequate hematologic, hepatic, and renal functions

          6. At least one measurable lesion

        Exclusion Criteria:

          1. Previous treatment with poziotinib prior to study participation.

          2. Brain metastases that are symptomatic or require therapy to control symptoms, as well
             as any history of radiation, surgery, or other therapy, including steroids, to control
             symptoms from brain metastases within 15 days of enrollment.

          3. Anticancer chemotherapy, biologics, immunotherapy, cure-intent radiotherapy, or
             investigational treatment within 15 days, except for hormone therapy, palliative
             therapy, or supportive therapy.

          4. History of congestive heart failure (CHF) Class III/IV according to the New York Heart
             Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring
             treatment.

          5. Patient has a cardiac ejection fraction <50%

          6. Patient has a history of other malignancies within the last 5 years

          7. Unable to take drugs orally

          8. Patient is pregnant or breast-feeding.