Abstract

Simple SummaryDevelopment of brain metastases is an important event for patients with breast cancer, and it affects both their survival and their quality of life. Patients with HER2-positive breast cancer are more commonly affected by brain metastases compared to patients with HER2-negative/hormone receptor-positive breast cancer. It is essential to find proper therapies that reduce the risk for metastasis in the brain, as well as agents that are active when metastatic lesions develop. Management of HER2-positive breast cancer has drastically improved in recent years due to the development of several drugs targeting the HER2 receptor. This review aims to provide insight into current and novel treatment strategies for patients with brain metastases from HER2-positive breast cancer.Development of brain metastases can occur in up to 30–50% of patients with breast cancer, representing a significant impact on an individual patient in terms of survival and quality of life. Patients with HER2-positive breast cancer have an increased risk of developing brain metastases; however, screening for brain metastases is not currently recommended due to the lack of robust evidence to support survival benefit. In recent years, several novel anti-HER2 agents have led to significant improvements in the outcomes of HER2-positive metastatic breast cancer. Despite these advances, brain and leptomeningeal metastases from HER2-positive breast cancer remain a significant cause of morbidity and mortality, and their optimal management remains an unmet need. This review presents an update on the current and novel treatment strategies for patients with brain metastases from HER2-positive breast cancer and discusses the open questions in the field.

Highlights

  • It is estimated that 30–50% of patients with metastatic breast cancer (MBC) will develop brain metastases (BM) [1,2]

  • This review focuses on the activity of the different anti-HER2 agents in patients with BM from HER2-positive MBC and, compared to other recent reviews [13], amounts to an update of the relevant evidence on systemic therapy, alone or in combination with radiotherapy, and it asks questions about prevention and/or early diagnosis of BM in this specific subgroup of patients

  • T-DM1 appears to have some activity in the context of BM, with progression-free survival (PFS) around 5–7 months, OS remains significantly inferior compared to patients without intracranial disease

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Summary

Introduction

It is estimated that 30–50% of patients with metastatic breast cancer (MBC) will develop brain metastases (BM) [1,2]. Other factors associated with BM were an age older than 70 years, the presence of more than two metastatic sites at MBC diagnosis, HR negativity and a more advanced stage of primary tumor [2,4] Despite this compelling evidence, screening for BM is currently not recommended due to a lack of data to support its benefit in terms of overall survival [5]. The best management of BM in breast cancer is not consensual, but it generally includes a combination of local interventions, such as surgery, whole-brain and/or stereotactic radiotherapy and systemic anticancer therapies [5,8] In many situations, such as leptomeningeal metastasis, recommendations are practically based on expert opinions [5].

Objective response
Trastuzumab–Pertuzumab
Lapatinib
Novel Agents Neratinib
Trastuzumab-Pertuzumab
Neratinib
Tucatinib
Pyrotinib
Margetuximab
Combination of Systemic Therapy with Radiotherapy
Trastuzumab
Challenges and Open Questions
A Single-center
Inflammatory breast cancer managed with curative intent
Findings
Conclusions
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