The Role of Circulating Tumor Cells in Chemoresistant Metastatic Breast Cancer

Breast cancer is the most frequent form of cancer among women and is one of the leading causes of death. Two routes of the metastatic process have been described: linear and parallel progression. A key factor is represented by circulating tumor cells (CTCs). CTCs detach from the primary tumor or develop from cancer stem cells (CSCs) that undergo epithelial-to-mesenchymal transition (EMT). CTCs migrate to the distant site where the reverse process occurs and a new tumor arises. One of the key problems of metastatic disease is chemoresistance, which leads to treatment failure and, eventually, death. The aim of this review is to present up-to-date data regarding the role of CTCs in chemoresistance in metastatic breast cancer (MBC) patients. A search in Cochrane Library and MEDLINE databases was performed. A total of 125 articles were identified. The results of the final 12 eligible studies revealed that CTCs having stem cell features and those with mesenchymal features are aggressive subtypes of cells that survive chemotherapy, being responsible for chemoresistance and thus for disease progression in MBC patients. The hemodynamic shear stress, alongside dynamic changes among CTCs during the disease, is also an important disease progression factor

Differentiating Breast Tumors from Background Parenchymal Enhancement at Contrast-Enhanced Mammography: The Role of Radiomics—A Pilot Reader Study

Background: The purpose of this study was to assess the effectiveness of the radiomic analysis of contrast-enhanced spectral mammography (CESM) in discriminating between breast cancers and background parenchymal enhancement (BPE). Methods: This retrospective study included 38 patients that underwent CESM examinations for clinical purposes between January 2019–December 2020. A total of 57 malignant breast lesions and 23 CESM examinations with 31 regions of BPE were assessed through radiomic analysis using MaZda software. The parameters that demonstrated to be independent predictors for breast malignancy were exported into the B11 program and a k-nearest neighbor classifier (k-NN) was trained on the initial groups of patients and was tested using a validation group. Histopathology results obtained after surgery were considered the gold standard. Results: Radiomic analysis found WavEnLL_s_2 parameter as an independent predictor for breast malignancies with a sensitivity of 68.42% and a specificity of 83.87%. The prediction model that included CH1D6SumAverg, CN4D6Correlat, Kurtosis, Perc01, Perc10, Skewness, and WavEnLL_s_2 parameters had a sensitivity of 73.68% and a specificity of 80.65%. Higher values were obtained of WavEnLL_s_2 and the prediction model for tumors than for BPEs. The comparison between the ROC curves provided by the WaveEnLL_s_2 and the entire prediction model did not show statistically significant results (p = 0.0943). The k-NN classifier based on the parameter WavEnLL_s_2 had a sensitivity and specificity on training and validating groups of 71.93% and 45.16% vs. 60% and 44.44%, respectively. Conclusion: Radiomic analysis has the potential to differentiate CESM between malignant lesions and BPE. Further quantitative insight into parenchymal enhancement patterns should be performed to facilitate the role of BPE in personalized clinical decision-making and risk assessment

The Role of miR-375-3p, miR-210-3p and Let-7e-5p in the Pathological Response of Breast Cancer Patients to Neoadjuvant Therapy

Background and Objectives: Prediction of response to therapy remains a continuing challenge in treating breast cancer, especially for identifying molecular tissue markers that best characterize resistant tumours. Microribonucleic acids (miRNA), known as master modulators of tumour phenotype, could be helpful candidates for predicting drug resistance. We aimed to assess the association of miR-375-3p, miR-210-3p and let-7e-5p in breast cancer tissues with pathological response to neoadjuvant therapy (NAT) and clinicopathological data. Material and methods: Sixty female patients diagnosed with invasive breast cancer at The Oncology Institute “Ion Chiricuță”, Cluj-Napoca, Romania (IOCN) were included in this study. Before patients received any treatment, fresh breast tissue biopsies were collected through core biopsy under echographic guidance and processed for total RNA extraction and miRNA quantification. The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) database was used as an independent external validation cohort. Results: miR-375-3p expression was associated with more differentiated tumours, hormone receptor presence and lymphatic invasion. According to the Miller–Payne system, a higher miR-375-3p expression was calculated for patients that presented with intermediate versus (vs.) no pathological response. Higher miR-210-3p expression was associated with an improved response to NAT in both Miller–Payne and RCB evaluation systems. Several druggable mRNA targets were correlated with miR-375-3p and miR-210-3p expression, with upstream analysis using the IPA knowledge base revealing a list of possible chemical and biological targeting drugs. Regarding let-7e-5p, no significant association was noticed with any of the analysed clinicopathological data. Conclusions: Our results suggest that tumours with higher levels of miR-375-3p are more sensitive to neoadjuvant therapy compared to resistant tumours and that higher miR-210-3p expression in responsive tumours could indicate an excellent pathological response