Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications

Abstract

Breast cancer that has metastasized to the brain presents difficult clinical challenges. This diagnosis comes with high mortality rates, largely due to complexities in early detection and ineffective therapies associated with both dormancy and impermeability of the blood-brain barrier (BBB). Magnetic resonance imaging (MRI) is the current gold standard for diagnosis and assessment of brain tumors. It has been used clinically to investigate metastatic development as well as monitor response to therapy. Here, we describe preclinical imaging strategies that we have used to study the development of brain metastases due to breast cancer. Using this approach, we have identified three subsets of metastatic disease: permeable metastases, nonpermeable metastases, and solitary, dormant cancer cells, which likely have very different biology and responses to therapy. The ability to simultaneously monitor the spatial and temporal distribution of dormant cancer cells, metastatic growth, and associated tumor permeability can provide great insight into factors that contribute to malignant proliferation. Our preclinical findings suggest that standard clinical detection strategies may underestimate the true metastatic burden of breast cancer that has metastasized to the brain. A better understanding of true metastatic burden in brains will be important to assist in the development of more effective chemotherapeutics-particularly those targeted to cross the BBB-as well as detection of small nonpermeable metastases.

The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation

“…This failure is mostly attributed to the lack of drug penetration through the blood-brain barrier (BBB). However, although the BBB is relevant for large molecules, such as trastuzumab, the blood-tumor barrier (BTB) is leakier, permitting drug delivery to BMs, especially at later stages of the disease (3, 4). Consistent with the BTB being leaky, both preclinical and clinical studies have shown some accumulation of anti-HER2 drugs in BMs (5, 6), but it remains unclear whether adequate drug concentrations are achieved in the clinical setting.…”

Emerging findings into molecular mechanism of brain metastasis

“…So the blood‐tumor barrier (BTB) is leakier than the intact BBB. If chemotherapy and radiation therapy were combined, it could allow delivery in brain lesions especially at advanced stages of disease 35. Nowadays, numerous techniques are developed to improve the delivery of therapeutics across the BBB, just like chemical modification of the drug,36 temporary disruption of the BBB 37 and so on.…”

Differentiating a simple cyst or metastatic breast cancer: A medical dilemma

“…Although the patient had been in remission from breast cancer for more than six years, and [1][2][3]. From this case, we can learn that the breast cancer may have been eradicated from the original source, but we should always be suspicious of the malignancy re-emerging in other parts of the body.…”