Emerging treatment strategies for breast cancer brain metastasis: from translational therapeutics to real-world experience

Abstract

Systemic therapies for primary breast cancer have made great progress over the past two decades. However, oncologists confront an insidious and particularly difficult problem: in those patients with metastatic breast cancer, up to 50% of human epidermal growth factor 2 (HER2)-positive and 25–40% of triple-negative subtypes, brain metastases (BM) kill most of them. Fortunately, standard- of-care treatments for BM have improved rapidly, with a decline in whole brain radiation therapy and use of fractionated stereotactic radiosurgery as well as targeted therapies and immunotherapies. Meanwhile, advances in fundamental understanding of the basic biological processes of breast cancer BM (BCBM) have led to many novel experimental therapeutic strategies. In this review, we describe the most recent clinical treatment options and emerging experimental therapeutic strategies that have the potential to combat BCBM.

Breast Cancer Subtypes and Mortality of Breast Cancer Patients With Brain Metastasis at Diagnosis: A Population-Based Study

“…33 The blood-brain barrier can make brain tumors difficult to treat using pharmacological agents, although some monoclonal antibodies and chemotherapy drugs are reasonable options for patients with BM. 7,34-36 Subgroup analysis in the present study revealed that the association between breast subtypes and mortality stably existed except in the case of primary surgery. Besides, the association was more significant in the chemotherapy group than non-chemotherapy participants (p for trend = .005).…”

Screening and Identification of Novel Potential Biomarkers for Breast Cancer Brain Metastases

“…Brain metastases are the most common malignant brain tumors and are the next frontier for the management of metastatic cancer patients (1,2). Even small lesions can cause neurological disability, and the median survival of patients with brain metastases is less than 1 year (3)(4)(5). Breast cancer is the second most frequent cause of brain metastases (3)(4)(5), and recently it has surpassed lung cancer as the leading cause of global cancer incidence (6).…”

“…Even small lesions can cause neurological disability, and the median survival of patients with brain metastases is less than 1 year (3)(4)(5). Breast cancer is the second most frequent cause of brain metastases (3)(4)(5), and recently it has surpassed lung cancer as the leading cause of global cancer incidence (6). Despite major advances over past decades in prolonging breast cancer survival, breast cancer brain metastases (BCBM) remain incurable with current therapies, and the incidence is steadily increasing (6,7).…”

“…HER2-targeted therapies have been shown to increase the time to development of brain metastases and improved survival following brain metastases (16,(18)(19)(20)(21), and patients with estrogen receptor-positive BCBM can be treated with endocrine agents, cyclin-dependent kinases 4/6 (CDK4/6) inhibitors, and the mechanistic target of rapamycin kinase (mTOR) inhibitors (17). Unfortunately, there is no effective targeted therapy for TNBC brain metastases (5,9,22). It is desirable to identify potential therapeutic targets or molecular risk factors or early biomarkers for this lethal disease.…”

Tubulin Tyrosine Ligase Like 4 (TTLL4) overexpression in breast cancer cells is associated with brain metastasis and alters exosome biogenesis

“…These cancer cells are highly aggressive and since most therapeutic compounds do not pass the blood-brain-barrier (BBB), they do not respond to hormone or chemotherapy. Clinical trials for new targeted therapies are in progress and the preliminary results are promising [1][2][3].…”