Radiotherapy for HER 2 Positive Brain Metastases: Urgent Need for a Paradigm Shift

SIMPLE SUMMARY: Brain metastases (BMs) are common among patients with advanced HER2 breast cancer. The recent introduction of systemic therapy with central nervous system activity as well as the wider use of brain stereotactic radiotherapy (SRT) are contributing to improving the outcomes for these patients. In this review, we discuss a modified approach to the treatment of HER2-positive BMs from a radiation oncologist point of view, taking into consideration new advances in multimodal therapy and combinations of the most commonly used systemic treatments and brain radiation therapy (RT). ABSTRACT: Brain metastases (BMs) are common among patients affected by HER2+ metastatic breast cancer (>30%). The management of BMs is usually multimodal, including surgery, radiotherapy, systemic therapy and palliative care. Standard brain radiotherapy (RT) includes the use of stereotactic radiotherapy (SRT) for limited disease and whole brain radiotherapy (WBRT) for extensive disease. The latter is an effective palliative treatment but has a reduced effect on brain local control and BM overall survival, as it is also associated with severe neurocognitive sequelae. Recent advances both in radiation therapy and systemic treatment may change the paradigm in this subset of patients who can experience long survival notwithstanding BMs. In fact, in recent studies, SRT for multiple BM sites (>4) has shown similar efficacy when compared to irradiation of a limited number of lesions (one to three) without increasing toxicity. These findings, in addition to the introduction of new drugs with recognized intracranial activity, may further limit the use of WBRT in favor of SRT, which should be employed for treatment of both multiple-site BMs and for oligo-progressive brain disease. This review summarizes the supporting literature and highlights the need for optimizing combinations of the available treatments in this setting, with a particular focus on radiation therapy.