• Participants must have a histological or cytological diagnosis of invasive breast cancer.

• All histologic subtypes are eligible.

• Participants must have a clinical diagnosis of stage III inflammatory breast cancer within the past 6 months

• HER2-positive status as determined locally by the current ASCO/CAP guidelines or HER2-low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested) (note: ISH may be determined by either fluorescence in situ hybridization \[FISH\] or dual in situ hybridization \[DISH\])

• Any ER and PR expressions are permitted but must be known

• Participants must be treatment-naïve

• Participants must agree to undergo two research biopsies of the tumor (if safely accessible, as determined by the treating investigator): at baseline (prior to the first treatment) and after the first week of treatment on C1D8. Previously collected archival tissue will also be obtained on all participants. For participants for whom the tumor is not safely accessible, this archival tissue needs to be located and availability confirmed at time of registration.

• Pre- and postmenopausal women or male patients ≥ 18 years of age

• ECOG performance status 0-1 (Karnofsky \> 60%, see Appendix A).

• LVEF ≥ 50% within 28 days prior to enrollment

• Participants must have normal organ and marrow function prior to enrollment as defined below:

‣ Absolute neutrophil count ≥2,000/mcL

⁃ Platelets ≥100,000/mcL

⁃ Hemoglobin ≥ 9.0 g/dl

⁃ INR/PT/aPTT ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is in therapeutic range of anticoagulant

⁃ Total bilirubin ≤1.5 × institutional upper limit of normal (ULN)(or ≤2.0 x ULN in patients with documented Gilbert's Syndrome)

⁃ AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN

⁃ Serum creatinine ≤1.5 × institutional ULN OR creatinine clearance ≥ 30 mL/min/ 1.73m2 for participants with creatinine levels above institutional ULN.

⁃ Serum albumin ≥2.5 g/dL

⁃ International normalized ratio (INR)/prothrombin time (PT) and either partial thromboplastin or activated partial thromboplastin time (aPTT) ≤1.5 × ULN

• Women of childbearing potential (WOCBP) and WOCBP who are partners of male participants must agree to use one highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception for the duration of study treatment with durvalumab and 7 months after the last dose of study treatment

• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with durvalumab and 4 months after the last dose of study treatment

• Must have a life expectancy of at least 12 weeks

• Body weight \>30 kg

• The participant must be capable of understanding and complying with the protocol and willing to sign a written informed consent document