Trastuzumab Deruxtecan (T-DXd) Alone or in Sequence With THP, Versus Standard Treatment (ddAC-THP), in HER2-positive Early Breast Cancer

Key Inclusion Criteria:

• Patients must be at least 18 years of age.

• Histologically documented HER2-positive early breast cancer (EBC) participants,including clinical stage at presentation (based on mammogram or breast MRIassessment): T0-4 (inclusive of inflammatory breast cancer), N1-3, M0 or ≥ T3, N0,M0 as determined by the AJCC staging system, 8th edition

• ECOG performance status of 0 or 1 at randomization

• Adequate organ and bone marrow function

• LVEF ≥ 50% within 28 days before randomization

• FFPE tissue block (2 cores) or 20 freshly-cut, serial tumor slides for HER2assessment by central lab. If blocks are incomplete or fewer than 20 slides areavailable, participants may be eligible following discussion with the AstraZenecaStudy Physician

Exclusion Criteria:

• prior history of invasive breast cancer

• stage IV breast cancer (determined by AJCC staging system)

• any primary malignancy within 3 years (except resected non-melanoma skin cancer,curatively treated in situ disease) Note: This includes a second current breastprimary malignancy (ie, bilateral breast cancer)

• history of DCIS (except those treated with mastectomy >5 years prior to currentdiagnosis)

• History of, or current, ILD/pneumonitis

• Prior systemic therapy for the treatment of breast cancer

• Previous treatment with anthracyclines, cyclophosphamide or taxanes for anymalignancy