HER2-positive breast cancer brain metastasis: A new and exciting landscape

Abstract

Background: Brain metastases (BrM) incidence is 25% to 50% in women with advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Radiation and surgery are currently the main local treatment approaches for central nervous system (CNS) metastases. Systemic anti-HER2 therapy following a diagnosis of BrM improves outcomes. Previous preclinical data has helped elucidate HER2 brain trophism, the blood-brain/blood-tumor barrier(s), and the brain tumor microenvironment, all of which can lead to development of novel therapeutic options.

Recent findings: Several anti-HER2 agents are currently available and reviewed here, some of which have recently shown promising effects in BrM patients, specifically. New strategies driven by and focusing on brain metastasis-specific genomics, immunotherapy, and preventive strategies have shown promising results and are under development.

Conclusions: The field of HER2+ breast cancer, particularly for BrM, continues to evolve as new therapeutic strategies show promising results in recent clinical trials. Increasing inclusion of patients with BrM in clinical studies, and a focus on assessing their outcomes both intracranially and extracranially, is changing the landscape for patients with HER2+ CNS metastases by demonstrating the ability of newer agents to improve outcomes.

Keywords: CNS involvement; HER2-positive breast cancer; T-DM1; brain metastasis; trastuzumab; tucatinib.

FIGURE 1

Suggested algorithm for multidisciplinary management of care for patients with HER2+ breast cancer brain metastases. BCBrM: breast cancer brain metastases; MBC: metastatic breast cancer; THP: Taxotere (Docetaxel) + Herceptin (Trastuzumab) + Perjeta (Pertuzumab); T‐DM1: ado‐trastuzumab emtansine (Kadcyla)