1. Has newly diagnosed Stage II or III histologically confirmed invasive breast carcinoma.
2. Has histologically confirmed HER2-positive breast cancer
3. Has a known hormone receptor (HR) status of the primary tumor
5. Agrees to undergo a mastectomy or breast conserving surgery (BCS) after neoadjuvant therapy.
6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. Adequate organ function
8. Has an LVEF ≥ 50% as determined by either ECHO or MUGA obtained within 6 weeks prior to randomization.
9. Adequate contraceptive precautions
10. Participants with known HIV are eligible unless:
1. CD4+ T Cell count is less than or equal to 350 microliters (uL)
2. Detectable viral load, or
3. Receiving protease inhibitors or cobicistat
You may not be if
1. Has Stage IV (metastatic) breast cancer.
2. Has bilateral breast cancer.
3. Has a history of any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the investigator, could affect the participant's involvement in the study.
4. Has uncontrolled hypertension
5. Has significant symptoms from peripheral neuropathy
6. Has an active uncontrolled infection
7. Has a history of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation of zanidatamab or other study interventions.
8. Known active hepatitis B or C infection.
10. Was treated with surgery, chemotherapy, anti-HER2 therapy, radiation therapy, endocrine therapy, or experimental therapy for invasive breast cancer
11. Is planning to receive concurrent therapy with any other investigational agent or anti-cancer therapy not specified in the protocol
12. Receipt of a live vaccine within 4 weeks prior to enrollment
13. Has a known hypersensitivity to any components of the study interventions, including chemotherapy
