fulvestrant + trastuzumab + tucatinib

This is a combination regimen of three drugs—fulvestrant, trastuzumab, and tucatinib—used primarily in the treatment of hormone receptor-positive (HR+), HER2-mutated metastatic breast cancer. - **Fulvestrant** is a selective estrogen receptor degrader (SERD) that binds to and accelerates degradation of the estrogen receptor, blocking estrogen signaling in tumor cells. - **Trastuzumab** is a monoclonal antibody targeting the extracellular domain of the HER2/neu (ERBB2) receptor, inhibiting downstream signaling pathways involved in cell proliferation and survival. - **Tucatinib** is an oral small molecule tyrosine kinase inhibitor highly selective for HER2, inhibiting its phosphorylation and subsequent activation of MAPK and AKT pathways. The triple combination has been investigated for patients with HR+/HER2-mutated metastatic breast cancer who have progressed on prior therapies. Clinical studies show this regimen can induce meaningful antitumor activity with durable responses in heavily pretreated patients[3][6][8]. The combination leverages dual blockade of HER2 signaling plus hormonal pathway inhibition to overcome resistance mechanisms seen in this patient population.