Inclusion Criteria:

          -  Pathologically-confirmed diagnosis of breast cancer with evidence of locally advanced
             (unresectable) and/or metastatic disease. All patients in both Parts 1 and 2 must have
             HER2-positive and HR-positive disease.

          -  Received prior treatment with trastuzumab, pertuzumab, AND ado-trastuzumab emtansine
             (T-DM1); disease progression during or after the most recent prior therapy. Patients
             in any part of the study who did not receive pertuzumab or T-DM1 because of lack of
             access (e.g., due to insurance coverage or because they were treated prior to
             regulatory agency approval of the agent in a relevant indication) or due to medical
             ineligibility for treatment with T-DM1 (e.g., history of severe infusion reactions to
             trastuzumab, >/= Grade 2 peripheral neuropathy, or platelet count < 100 x 10^9/L) may
             be eligible for the study. Prior treatment with endocrine therapy in the neoadjuvant,
             adjuvant, and/or metastatic setting is permitted.

          -  Sites of disease assessible per RECIST version 1.1 (both measurable and non-measurable
             disease allowed)

          -  An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

          -  Adequate organ function

          -  Adequate cardiac left ventricular function, as defined by left ventricular ejection
             fraction (LVEF) >/= institutional standard of normal

        Exclusion Criteria:

          -  Prior treatment with trastuzumab, pertuzumab, lapatinib, T-DM1, or other
             anti-HER2-targeted therapy </= 3 weeks before the first dose of ZW25

          -  Prior treatment with chemotherapy, other anti-cancer therapy not otherwise specified,
             or hormonal cancer therapy </= 3 weeks before the first dose of ZW25

          -  Prior treatment with palbociclib or any other CDK4/6 inhibitor, including experimental
             agents

          -  History of myocardial infarction or unstable angina within 6 months prior to
             enrollment, troponin levels consistent with myocardial infarction, or clinically
             significant cardiac disease, such as ventricular arrhythmia requiring therapy,
             uncontrolled hypertension, or any history of symptomatic congestive heart failure
             (CHF)

          -  QTc Fridericia (QTcF) > 470 ms

          -  Grade 2 or greater pneumonitis and/or interstitial lung disease, including pulmonary
             fibrosis, or other clinically significant infiltrative pulmonary disease not related
             to lung metastases

          -  Active hepatitis B or hepatitis C infection

          -  Acute or chronic uncontrolled renal disease, pancreatitis, or severe liver disease
             (Child-Pugh Class C)

          -  Known infection with Human Immunodeficiency Virus (HIV)-1 or HIV-2 (Exception:
             patients with well controlled-HIV [e.g., cluster of differentiation 4 (CD4)-positive
             T-cell count > 350 mm3 and undetectable viral load] are eligible.)

          -  Prior or concurrent malignancy whose natural history or treatment has the potential to
             interfere with the safety or efficacy assessment of the investigational regimen

          -  Brain metastases: Untreated central nervous system (CNS) metastases, symptomatic CNS
             metastases, or radiation treatment for CNS metastases within 4 weeks of start of study
             treatment. Stable, treated brain metastases are allowed (defined as patients who are
             off steroids and anticonvulsants and are neurologically stable for at least 1 month at
             the time of screening).

          -  History of or ongoing leptomeningeal disease

          -  Grade 3 or greater peripheral neuropathy