Management of Brain and Leptomeningeal Metastases from Breast Cancer.

Alessia Pellerino,Valeria Internò,Riccardo Soffietti,Francesca Mo,Roberta Rudà,Federica Franchino

doi:10.3390/ijms21228534

Abstract

The management of breast cancer (BC) has rapidly evolved in the last 20 years. The improvement of systemic therapy allows a remarkable control of extracranial disease. However, brain (BM) and leptomeningeal metastases (LM) are frequent complications of advanced BC and represent a challenging issue for clinicians. Some prognostic scales designed for metastatic BC have been employed to select fit patients for adequate therapy and enrollment in clinical trials. Different systemic drugs, such as targeted therapies with either monoclonal antibodies or small tyrosine kinase molecules, or modified chemotherapeutic agents are under investigation. Major aims are to improve the penetration of active drugs through the blood–brain barrier (BBB) or brain–tumor barrier (BTB), and establish the best sequence and timing of radiotherapy and systemic therapy to avoid neurocognitive impairment. Moreover, pharmacologic prevention is a new concept driven by the efficacy of targeted agents on macrometastases from specific molecular subgroups. This review aims to provide an overview of the clinical and molecular factors involved in the selection of patients for local and/or systemic therapy, as well as the results of clinical trials on advanced BC. Moreover, insight on promising therapeutic options and potential directions of future therapeutic targets against BBB and microenvironment are discussed.

Highlights

Breast cancer (BC) is the second most common solid tumor that can metastasize to CNS
breast cancer (BC) were classified based on the 2015 ESMO Guidelines [4] in five molecular subtypes: luminal A, luminal B human epidermal growth factor receptor 2 (HER2)-negative (ER+, HER2, high ki67, or low PR+), luminal B HER2-positive (ER+, HER2+, any PR, any ki67), HER2-enriched (HER2+, ER, PR-), and “basal like” or triple negative BC (ER, PR, HER2-negative/TNBC)
The analysis showed that the molecular subtypes were significantly correlated with OS (p < 0.0001): 3.1 months for TNBC, 3.9 months for luminal B HER2-negative, 7.1 months for luminal A, 12.1 months for HER2-enriched, and 15.4 months for luminal B HER2-positive, respectively [3]

Summary

Introduction

Breast cancer (BC) is the second most common solid tumor that can metastasize to CNS. Patients with ≥ 2 WBC (white blood cells)/mm (HR 3.4; 95%CI 1.8–5.0), glucose levels ≥ 3 mmol/L (HR 7.4, 95%CI 4.7–10.0), and protein levels ≥1 g/L (HR 2.4; 95%CI 0.6–4.3) in cerebrospinal fluid (CSF) had a significantly shorter median OS [8]. Another cohort of 187 LM from BC treated from 1999 to 2015 showed a median OS of 4.2 months with a 6- and 12-months OS of 34 and 15%, respectively [9].

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Results

Conclusion