Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.

The molecular receptor status of breast cancer has implications for prognosis and long-term metastasis. Although metastatic luminal B-like, hormone-receptor-positive, HER2−negative, breast cancer causes brain metastases less frequently than other subtypes, though tumor metastases in the brain are increasingly being detected of this patient group. Despite the many years of tried and tested use of a wide variety of anti-hormonal therapeutic agents, there is insufficient data on their intracerebral effectiveness and their ability to cross the blood-brain barrier. In this review, we therefore summarize the current state of knowledge on anti-hormonal therapy and its intracerebral impact and effects on the blood-brain barrier in breast cancer.

Background: Pelvic palpation is a core component of every Gynecologic examination. It requires vigorous training, which is difficult due to its intimate nature, leading to a need of simulation. Up until now, there are mainly models available for mere palpation which do not offer adequate visualization of the concerning anatomical structures. In this study we present a 3D printed model of the female pelvis. It can improve both the practical teaching of gynecological pelvic examination for health care professionals and the spatial understanding of the relevant anatomy. Methods: We developed a virtual, simplified model showing selected parts of the female pelvis. 3D printing was used to create a physical model. Results: The life-size 3D printed model has the ability of being physically assembled step by step by its users. Consequently, it improves teaching especially when combining it with commercial phantoms, which are built solely for palpation training. This is achieved by correlating haptic and visual sensations with the resulting feedback received. Conclusion: The presented 3D printed model of the female pelvis can be of aid for visualizing and teaching pelvic anatomy and examination to medical staff. 3D printing provides the possibility of creating, multiplying, adapting and sharing such data worldwide with little investment of resources. Thus, an important contribution to the international medical community can be made for training this challenging examination.

Brain metastases are a major cause of death in breast cancer patients. A key event in the metastatic progression of breast cancer in the brain is the migration of cancer cells across the blood-brain barrier (BBB). The BBB is a natural barrier with specialized functions that protect the brain from harmful substances, including antitumor drugs. Extracellular vesicles (EVs) sequestered by cells are mediators of cell-cell communication. EVs carry cellular components, including microRNAs that affect the cellular processes of target cells. Here, we summarize the knowledge about microRNAs known to play a significant role in breast cancer and/or in the BBB function. In addition, we describe previously established in vitro BBB models, which are a useful tool for studying molecular mechanisms involved in the formation of brain metastases.

Herbert SL, et al. J Breast Cancer. 2023 May;26:e23. https://doi.org/10.4048/jbc.2023.26.e23

With increasing spatial resolution, diffusion-weighted imaging (DWI) may be suitable for morphologic lesion characterization in breast MRI - an area that has traditionally been occupied by dynamic contrast-enhanced imaging (DCE). This investigation compared DWI with b values of 800 and 1600 s/mm² to DCE for lesion morphology assessment in high-resolution breast MRI at 3 Tesla. Multiparametric breast MRI was performed in 91 patients with 93 histopathologically proven lesions (31 benign, 62 malignant). Two radiologists independently evaluated three datasets per patient (DWI_b800; DWI_b1600; DCE) and assessed lesion visibility and BIRADS morphology criteria. Diagnostic accuracy was compared among readers and datasets using Cochran's Q test and pairwise post-hoc McNemar tests. Bland-Altman analyses were conducted for lesion size comparisons. Discrimination of carcinomas was superior compared to benign findings in both DWI_b800 and DWI_b1600 (p < 0.001) with no b value-dependent difference. Similarly, assessability of mass lesions was better than of non-mass lesions, irrespective of b value (p < 0.001). Intra-reader reliability for the analysis of morphologic BIRADS criteria among DCE and DWI datasets was at least moderate (Fleiss κ≥0.557), while at least substantial inter-reader agreement was ascertained over all assessed categories (κ≥0.776). In pairwise Bland-Altman analyses, the measurement bias between DCE and DWI_b800 was 0.7 mm, whereas the difference between DCE and DWI_b1600 was 2.8 mm. DWI_b1600 allowed for higher specificity than DCE (p = 0.007/0.062). DWI can be employed for reliable morphologic lesion characterization in high-resolution breast MRI. High b values increase diagnostic specificity, while lesion size assessment is more precise with standard 800 s/mm² images.