Progressively Enlarging Cerebellar Hematoma Concurrent with T-DM1 Treatment

Trastuzumab emtansine, an antibody-drug conjugate commonly abbreviated as T-DM1, is accepted as effective therapy for trastuzumab-resistant metastatic HER2-positive breast cancer. T-DM1 significantly increases progression-free and overall survival when compared with lapatinib plus capecitabine in patients with HER2-positive breast cancer previously treated with trastuzumab and a taxane. Among the common side effects related to T-DM1, thrombocytopenia and mucosal hemorrhage are seen, although they are infrequently judged to be clinically significant. Intracranial hemorrhages are extremely rare, and only 3 cases of hematomas have been reported in association with T-DM1 and remote radiotherapy, 2 of them with progressive enlargement.

Herein we describe a patient who presented with a cerebellar hematoma that progressively enlarged over 8 months during treatment with T-DM1 and only a few months after whole-brain radiation therapy plus a stereotactic radiosurgery boost for a HER2-positive breast cancer cerebellar metastasis. The pathology of the hematoma was similar to that in previous cases and suggested a unique pathophysiology related to an interaction between T-DMI and radiation therapy.

A progressively enlarging intraparenchymal hematoma can be seen just a few months after delivery of radiation therapy for a metastatic brain lesion in HER2-positive breast cancer patients who are receiving T-DM1. In such patients, even a small focus of hemorrhage on magnetic resonance images should prompt close follow-up with serial imaging.