Would you consider using tucatinib in a patient with de-novo metastatic HER2+ HR(-) breast cancer patient with extensive intraparenchymal and leptomeningeal carcinomatosis?

Absolutely. The HER2CLIMB regimen is well known to have good CNS penetration. There is an ongoing trial looking at this regimen in Her2+ leptomeningeal disease (TBCRC049). Given the pacity of studied regimens/data in leptomeningeal disease, this is an excellent option. Other options include T Dx'd - there are studies looking into brain penetration and case reports of response in leptomeningeal disease and intrathecal trastuzumab.