Understanding Patterns of Brain Metastasis in Triple-Negative Breast Cancer and Exploring Potential Therapeutic Targets

Abstract

Triple-negative breast cancer (TNBC) is a highly malignant subtype of breast cancer. High invasiveness and heterogeneity, as well as a lack of drug targets, are the main factors leading to poor prognosis. Brain metastasis (BM) is a serious event threatening the life of breast cancer patients, especially those with TNBC. Compared with that for hormone receptor-positive and HER2-positive breast cancers, TNBC-derived BM (TNBCBM) occurs earlier and more frequently, and has a worse prognosis. There is no standard treatment for BM to date, and one is urgently required. In this review, we discuss the current knowledge regarding the developmental patterns of TNBCBM, focusing on the key events in BM formation. Specifically, we consider (i) the nature and function of TNBC cells; (ii) how TNBC cells cross the blood-brain barrier and form a fenestrated, more permeable bloodtumor barrier; (iii) the biological characteristics of TNBCBM; and (iv) the infiltration and colonization of the central nervous system (CNS) by TNBC cells, including the establishment of premetastatic niches, immunosurveillance escape, and metabolic adaptations. We also discuss putative therapeutic targets and precision therapy with the greatest potential to treat TNBCBM, and summarize the relevant completed and ongoing clinical trials. These findings may provide new insights into the prevention and treatment of BM in TNBC patients.

Glucose Transporters as a Target for Anticancer Therapy

“…It is highly malignant, invasive, and chemoresistant. This cancer is defined by the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression [65].…”

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.…”

“…Encephalitis is a brain inflammation disease often caused by infection (Mailles et al., 2017 ). The pathology of brain inflammation cascade is associated with increased migration of immune cells utilizing diapedesis and chemotaxis from blood to brain, crossing the BBB, which breaks down during brain inflammation.…”

A common goal to CARE: Cancer Advocates, Researchers, and Clinicians Explore current treatments and clinical trials for breast cancer brain metastases

“…Several contributing factors include increased detection due to improved and more widely available radiological techniques and targeted therapies to treat systemic disease, which prolong survival 14 , 15 . The extended survival time has led to a 25–40% increased incidence in brain metastasis in patients with HER2-positive breast cancer and as high as 46% among patients with advanced TNBC 14 , 16 , 17 .…”