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.

Pyrotinib Treatment in Patients With HER2-positive Metastatic Breast Cancer and Brain Metastasis: Exploratory Final Analysis of Real-World, Multicenter Data

“…Moreover, the survival of these patients is generally poor, and the median overall survival (OS) after the initial diagnosis of CNS metastases is 13.0 months 6 . Although anti-HER2 therapeutic options have steadily enhanced the effect of systemic therapy on patients with HER2+ metastatic breast cancer (MBC), there is an increased awareness that clinical strategies targeting BM are needed for this subtype of BC 7 .…”

From blood to brain: blood cell-based biomimetic drug delivery systems

“…Macrophages, like monocytes, can cross the BBB and may be able to infiltrate the tumor. Brain metastasis is prevalent in subtypes (triple-negative and HER2 þ ) of breast cancer (Zimmer et al, 2020;Lv et al, 2021). Choi et al first reported that macrophages-mediated delivery of nanoparticles for brain delivery.…”

Trastuzumab deruxtecan in HER2-positive metastatic breast cancer and beyond

“…Brain metastases are common in patients with HER2positive mBC; it is estimated that brain metastases will ultimately develop in 25-50% of female patients [32]. Even after treatment with whole brain radiotherapy, brain metastases have a negative impact on patients' quality of life and outcome [33], highlighting the need for more effective treatments.…”

“…Even after treatment with whole brain radiotherapy, brain metastases have a negative impact on patients' quality of life and outcome [33], highlighting the need for more effective treatments. Trastuzumab has low central nervous system penetrance and is not effective at treating brain metastases compared with HER2-targeted therapies in development, such as tucatinib [32,[34][35][36]. Long-term follow-up of patients with HER2-positive CRC treated with trastuzumab and lapatinib also showed the central nervous system to be a 'sanctuary site' of relapse [37,38].…”