Breast Cancer with Brain Metastasis: Molecular Insights and Clinical Management

Abstract

Breast cancer is the most frequently diagnosed malignancy worldwide and the leading cause of cancer-related death among women. Brain metastases are a primary contributor to mortality, as they often go undetected until late stages due to their dormant nature. Moreover, the clinical management of brain metastases is complicated by the relevant issue of blood-brain barrier penetration. The molecular pathways involved in the formation, progression, and colonization of primary breast tumors and subsequent brain metastases are diverse, posing significant hurdles due to the heterogeneous nature of breast cancer subtypes. Despite advancements in primary breast cancer treatments, the prognosis for patients with brain metastases remains poor. In this review, we aim to highlight the biological mechanisms of breast cancer brain metastases by evaluating multi-step genetic pathways and to discuss currently available and emerging treatment strategies to propose a prospective overview of the management of this complex disease.

Intracranial Efficacy of Pyrotinib and Capecitabine Combination Therapy in HER2-Positive Breast Cancer with Brain Metastases

“… 11 Additionally, chemotherapy, endocrine therapy, and anti-HER2 targeted therapy often yield limited results, which could be attributed to the inadequate ability of drugs in penetrating the blood–brain barrier. 12 …”

Magnetic Particle Imaging Reveals that Iron-Labeled Extracellular Vesicles Accumulate in Brains of Mice with Metastases

“…Although there have been advances in treating the primary tumor, metastases continue to be the leading cause of death among these patients . In particular, up to 30% of breast cancer patients have brain metastases, , and the prognosis for these patients is poor with a survival rate of only 20% at 1 year. − …”

“… 2 In particular, up to 30% of breast cancer patients have brain metastases, 2 , 3 and the prognosis for these patients is poor with a survival rate of only 20% at 1 year. 3 − 6 …”

Clinico–pathologic Factors and Survival of Patients with Breast Cancer Diagnosed with De Novo Brain Metastasis: A National Cancer Database Analysis

“…Additionally, BCBM require treatment based on the primary tumor characteristics including chemotherapy, hormonal, and anti-HER2 targeted therapy [12,13]. There is a growing number of studies and clinical trials investigating newer targeted therapies for BCBM which span different classes such as EGFR receptor modulators, tyrosine kinase inhibitors, and CDK4/6 inhibitors to name a few [14][15][16][17][18][19][20][21][22]. Despite our growing knowledge about BCBM and the many efforts to identify prognostic and therapeutic interventions, large population-based survival studies on de novo BCBM remain lacking.…”