Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis

Abstract

Background: Brain metastasis (BM) are a major clinical problem in metastatic breast cancer (MBC), occurring in 50% of patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Historically omitted from clinical trials, recent studies of novel HER2-targeted agents have focused on HER2+ BM patients, addressing stable but also progressing BM and leptomeningeal carcinomatosis (LMC). Summary: This review aims to summarise the most relevant data on treating patients with HER2+ BM and LMC. Key messages: The treatment paradigm for patients with HER2+ MBC has changed. Local therapies play an important role, but accumulating evidence on the intracranial activity and clinical benefit of anti-HER2 targeting therapies might lead to a shift in the paradigm on treating BM in the next few years towards more widespread use of systemic therapy.

Evolution of HER2 Targeting in Metastatic Breast Cancer

“…With ever improving systemic disease control, brain metastases have become a major clinical challenge as up 522 DOI: 10.1159/000528002 to 50% of patients with HER2-positive metastatic disease will eventually be diagnosed with this devastating complication. The clinical relevance has led to increased scientific interest and growing understanding with regards to systemic treatment options, as reviewed by Vaz Batista et al [11] Indeed, the introduction of tucatinib and T-DXd has further bolstered the concept of systemic therapy as a potential treatment standard, specifically aiming at avoiding -or at least delaying -the need for whole brain radiotherapy.…”