Using a NF1-deficent ER+ patient-derived xenograft (PDX) mouse model (WHIM16), we determined that marked tumor regression can be achieved with the combination of fulvestrant (F), which is a pure ER antagonist and degrader, and the MEK inhibitor binimetinib (B), to inhibit RAS signaling downstream of RAF (9). Here, NF1 is linked to neoplasm.