Trastuzumab emtansine and stereotactic radiosurgery: an unexpected increase in clinically significant brain edema

Neuro Oncol. 2014 Jul;16(7):1006-9. doi: 10.1093/neuonc/not329.


Background: In the last 10 years, multiple new targeted agents have been developed for patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. Up to 55% of patients with HER2+ breast cancer will develop brain metastases requiring some form of radiation therapy. The interaction between radiation and these targeted agents is unknown and previously unreported.

Methods: In this series, we describe 4 patients who developed clinically significant brain edema at sites of treated brain metastases. These patients were treated with stereotactic radiosurgery and trastuzumab emtansine, the newest FDA-approved agent for metastatic HER2+ breast cancer. Additionally, we present rates of clinically significant radiation necrosis among all breast cancer patients treated during this same time period.

Results: Using previously published clinical and preclinical data, we then hypothesize possible mechanisms for this striking interaction.

Conclusion: Increased awareness of potential interactions between targeted agents and radiation to the brain is crucial.

MeSH terms

  • Ado-Trastuzumab Emtansine
  • Adult
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects*
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects*
  • Brain / drug effects
  • Brain / pathology
  • Brain / radiation effects
  • Brain Edema / etiology*
  • Brain Edema / pathology
  • Brain Neoplasms / secondary*
  • Brain Neoplasms / therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Combined Modality Therapy / adverse effects
  • Female
  • Humans
  • Maytansine / administration & dosage
  • Maytansine / adverse effects
  • Maytansine / analogs & derivatives*
  • Middle Aged
  • Necrosis / etiology
  • Radiosurgery / adverse effects*
  • Receptor, ErbB-2 / biosynthesis
  • Receptor, ErbB-2 / genetics
  • Trastuzumab


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Maytansine
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab
  • Ado-Trastuzumab Emtansine