How would you approach a patient with gBRCA mutated, ER+,HER2- metastatic breast cancer with brain mets refractory to WBRT and chemotherapy?

There are several options. I would consider a PARP inhibitor, as there is likely activity in this setting as these small molecules likely cross the blood brain barrier. There is also activity (although modest) of abemaciclib as well in this setting. We also should remember that anti hormonal agents are of use and can result in prolonged CNS responses as well.

This is a difficult situation to be in but with the approval of Olaparib and Talazoparib - 2 PARP inhibitors- based on the OlympiAD and EMBRACA studies, respectively, these would be options to consider. One must remember that the EMBRACA study had about 15% patients with CNS disease, but for inclusion in the trial, the CNS disease had to be treated and stable. OlympiAD just stratified data based on bone only vs metastases elsewhere and did not specifically report data for CNS metastases. Neverth...