TReatment of ADC-Refractory Breast CancEr With Dato-DXd or T-DXd: TRADE DXd

Participants must have histologically or cytologically confirmed invasive breast cancer with unresectable locally advanced or metastatic disease. Participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation; i.e., visible chest wall disease or metastases on imaging meeting standard radiology criteria (i.e., lymph nodes larger than 1 cm in the short axis diameter).

The most recent pathology results will be considered for enrollment according to local testing of ER, PR and HER2 in a CLIA-certified environment. ER, PR and HER2 status per local testing must be known prior to study registration.

Participants must have history of HER2-low or HER2-0 breast cancer per local testing, and no known history of HER2-positive breast cancer. All available prior HER2 pathology results must be HER2-low or HER2-0; no known HER2 IHC 3+ or ISH-amplified breast cancer is allowed.

HER2-low status is defined as IHC 1+ or 2+/ISH non-amplified breast cancer in any prior tumor sample (e.g., primary or metastatic tumor) collected prior to study enrollment: 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])