Our findings revealed synergistic effects in HER2-low BC patient-derived organoids when treated with T-Dxd and or trastuzumab in combination with durvalumab. We also observed antibody-dependent cellular cytotoxicity (ADCC) response with trastuzumab in combination with durvalumab....Altogether, despite preliminary, these findings support the rationale for combining anti-HER2 therapies with immunotherapy in HER2-low BC patients.