Trial of Trastuzumab Deruxtecan in Previously Treated HER2

Inclusion criteria

• . Must be competent and able to comprehend, sign, and date an Institutional Review Board (IRB) approved ICF before performance of any study-specific procedures or tests.
• . Men or women ≥18 years old.
• . Pathologically documented breast cancer that is unresectable or metastatic.
• . 4.Tumor biopsies have always shown HER2-IHC 0 (\<10% membrane staining, including 0 null and 0 ultralow) in all prior biopsies and never previously HER2-positive (IHC 3+ or ISH+) or HER2-low (1+, or 2+ ISH-) on prior pathology testing according to American Society of Clinical Oncology College of American Pathologists (ASCO-CAP) guidelines.
• . Either HR-positive or HR-negative status of the tumor per ASCO-CAP guidelines are allowed.
• . Patients with HR-positive disease must have progressed or be intolerant to CDK 4/6 inhibitors plus endocrine therapy, and patients with HR-negative disease must have received 1 line of therapy in the metastatic setting (progression on or within 6 months of neoadjuvant or adjuvant therapy will be accounted for as 1 line of prior therapy). There is no limit on number of subsequent lines of therapy for study entry. .
• . Patients must have never been previously treated with any anti-HER2 therapy, including prior trastuzumab deruxtecan, other HER2-directed ADCs, HER2 antibodies or HER2 tyrosine kinase inhibitors
• . Clinical or radiologic progression (during or after most recent treatment) or intolerance to therapy prior to enrollment in this trial

Exclusion criteria