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Background: Developing trustworthy artificial intelligence (AI) models for clinical applications requires access to clinical and imaging data cohorts. Reusing of publicly available datasets has the potential to fill this gap. Specifically in the domain of breast cancer, a large archive of publicly accessible medical images along with the corresponding clinical data is available at The Cancer Imaging Archive (TCIA). However, existing datasets cannot be directly used as they are heterogeneous and cannot be effectively filtered for selecting specific image types required to develop AI models. This work focuses on the development of a homogenized dataset in the domain of breast cancer including clinical and imaging data. Methods: Five datasets were acquired from the TCIA and were harmonized. For the clinical data harmonization, a common data model was developed and a repeatable, documented "extract-transform-load" process was defined and executed for their homogenization. Further, Digital Imaging and COmmunications in Medicine (DICOM) information was extracted from magnetic resonance imaging (MRI) data and made accessible and searchable. Results: The resulting harmonized dataset includes information about 2,035 subjects with breast cancer. Further, a platform named RV-Cherry-Picker enables search over both the clinical and diagnostic imaging datasets, providing unified access, facilitating the downloading of all study imaging that correspond to specific series' characteristics (e.g., dynamic contrast-enhanced series), and reducing the burden of acquiring the appropriate set of images for the respective AI model scenario. Conclusions: RV-Cherry-Picker provides access to the largest, publicly available, homogenized, imaging/clinical dataset for breast cancer to develop AI models on top. Relevance statement: We present a solution for creating merged public datasets supporting AI model development, using as an example the breast cancer domain and magnetic resonance imaging images. Key points: • The proposed platform allows unified access to the largest, homogenized public imaging dataset for breast cancer. • A methodology for the semantically enriched homogenization of public clinical data is presented. • The platform is able to make a detailed selection of breast MRI data for the development of AI models. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer therapy-related cardiac dysfunction (CTRCD) has been an urgent medical issue in patients that receive breast cancer therapies including anthracycline-based chemotherapies and/or targeted anti-HER2 therapies such as trastuzumab. Traditional biomarkers used as standard of care may be useful indicators of cardiac damage but their use to predict the onset of CTRCD lacks reliability. Ongoing clinical studies aim to explore new insights into the use of traditional biomarkers and investigate the promising role of novel biomarkers as reliable indicators and/or predictors of CTRCD. Patients with breast cancer could benefit from an alternative cardiac risk stratification plan that has the potential to predict the onset of CTRCD and/or detect CTRCD at early stages. The aim of this systematic review is to provide an overview of the human studies, which explore novel insights into traditional biomarkers and/or novel biomarkers that can be used for the early detection and/or prediction of CTRCD in breast cancer patients undergoing cardiotoxic-cancer therapies. Cardiotoxicity induced by breast cancer therapies is a potentially serious complication associated with the use of various breast cancer therapies. Prediction and better management of cardiotoxicity in patients receiving chemotherapy is of critical importance. However, the management of cancer therapy-related cardiac dysfunction (CTRCD) lacks clinical evidence and is based on limited clinical studies. Aim: To provide an overview of existing and potentially novel biomarkers that possess a promising predictive value for the early and late onset of CTRCD in the clinical setting. Methods: A systematic review of published studies searching for promising biomarkers for the prediction of CTRCD in patients with breast cancer was undertaken according to PRISMA guidelines. A search strategy was performed using PubMed, Google Scholar, and Scopus for the period 2013–2023. All subjects were >18 years old, diagnosed with breast cancer, and received breast cancer therapies. Results: The most promising biomarkers that can be used for the development of an alternative risk cardiac stratification plan for the prediction and/or early detection of CTRCD in patients with breast cancer were identified. Conclusions: We highlighted the new insights associated with the use of currently available biomarkers as a standard of care for the management of CTRCD and identified potentially novel clinical biomarkers that could be further investigated as promising predictors of CTRCD. [ABSTRACT FROM AUTHOR]

Identifying individual patient characteristics that contribute to long-term mental health deterioration following diagnosis of breast cancer (BC) is critical in clinical practice. The present study employed a supervised machine learning pipeline to address this issue in a subset of data from a prospective, multinational cohort of women diagnosed with stage I–III BC with a curative treatment intention. Patients were classified as displaying stable HADS scores (Stable Group; n = 328) or reporting a significant increase in symptomatology between BC diagnosis and 12 months later (Deteriorated Group; n = 50). Sociodemographic, life-style, psychosocial, and medical variables collected on the first visit to their oncologist and three months later served as potential predictors of patient risk stratification. The flexible and comprehensive machine learning (ML) pipeline used entailed feature selection, model training, validation and testing. Model-agnostic analyses aided interpretation of model results at the variable- and patient-level. The two groups were discriminated with a high degree of accuracy (Area Under the Curve = 0.864) and a fair balance of sensitivity (0.85) and specificity (0.87). Both psychological (negative affect, certain coping with cancer reactions, lack of sense of control/positive expectations, and difficulties in regulating negative emotions) and biological variables (baseline percentage of neutrophils, thrombocyte count) emerged as important predictors of mental health deterioration in the long run. Personalized break-down profiles revealed the relative impact of specific variables toward successful model predictions for each patient. Identifying key risk factors for mental health deterioration is an essential first step toward prevention. Supervised ML models may guide clinical recommendations toward successful illness adaptation. [ABSTRACT FROM AUTHOR]

Imaging biomarkers (IBs) play a critical role in the clinical management of breast cancer (BRCA) patients throughout the cancer continuum for screening, diagnosis, and therapy assessment, especially in the neoadjuvant setting. However, certain model-based IBs suffer from significant variability due to the complex workflows involved in their computation, whereas model-free IBs have not been properly studied regarding clinical outcome. In this study, IBs from 35 BRCA patients who received neoadjuvant chemotherapy (NAC) were extracted from dynamic contrast-enhanced MR imaging (DCE-MRI) data with two different approaches, a model-free approach based on pattern recognition (PR), and a model-based one using pharmacokinetic compartmental modeling. Our analysis found that both model-free and model-based biomarkers can predict pathological complete response (pCR) after the first cycle of NAC. Overall, eight biomarkers predicted the treatment response after the first cycle of NAC, with statistical significance (p-value < 0.05), and three at the baseline. The best pCR predictors at first follow-up, achieving high AUC and sensitivity and specificity more than 50%, were the hypoxic component with threshold 2 (AUC 90.4%) from the PR method, and the median value of kep (AUC 73.4%) from the model-based approach. Moreover, the 80th percentile of ve achieved the highest pCR prediction at baseline with AUC 78.5%. The results suggest that the model-free DCE-MRI IBs could be a more robust alternative to complex, model-based ones such as kep and favor the hypothesis that the PR image-derived hypoxic image component captures actual tumor hypoxia information able to predict BRCA NAC outcome. [ABSTRACT FROM AUTHOR]

MRI Imaging biomarkers (IBs) have the potential to deliver quantitative cancer descriptors of pathophysiology for non-invasively screening, diagnosing, and monitoring cancer patients across the cancer continuum. Despite a worldwide effort to standardize IBs involving major cancer organizations, significant variability of MR-based imaging biomarker across sites still hampers their clinical translation calling for more research in the field. To this end, in the present study quantitative and semi-quantitative approaches for perfusion biomarkers are compared in MRI data from three different cancer types. In particular, Ktrans a widely used but often variable across sites candidate biomarker is compared to a semi-quantitative perfusion MRI imaging biomarker (Wash-in WIN) in patients with breast, head, and neck and soft tissue sarcoma. Our results demonstrated a linear relationship between WIN and Ktrans in all cancer patients groups when a goodness of fit (high $\bar{R}^2$) criterion for ensuring adequate data quality and accuracy is met. This consistent correlation across three different cancer types indicates that the proposed semi-quantitative perfusion MRI IB can be a simpler, more robust and reproducible alternative to Ktrans for quantitative perfusion studies in oncology. [ABSTRACT FROM AUTHOR]

This paper outlines the major components and function of the technologically integrated oncosimulator developed primarily within the Advancing Clinico Genomic Trials on Cancer (ACGT) project. The Oncosimulator is defined as an information technology system simulating in vivo tumor response to therapeutic modalities within the clinical trial context. Chemotherapy in the neoadjuvant setting, according to two real clinical trials concerning nephroblastoma and breast cancer, has been considered. The spatiotemporal simulation module embedded in the Oncosimulator is based on the multiscale, predominantly top-down, discrete entity—discrete event cancer simulation technique developed by the In Silico Oncology Group, National Technical University of Athens. The technology modules include multiscale data handling, image processing, invocation of code execution via a spreadsheet-inspired environment portal, execution of the code on the grid, and the visualization of the predictions. A refining scenario for the eventual coupling of the oncosimulator with immunological models is also presented. Parameter values have been adapted to multiscale clinical trial data in a consistent way, thus supporting the predictive potential of the oncosimulator. Indicative results demonstrating various aspects of the clinical adaptation and validation process are presented. Completion of these processes is expected to pave the way for the clinical translation of the system. [ABSTRACT FROM PUBLISHER]

This study aimed to investigate which of the two frequently adopted perfusion models better describes the contrast enhanced ultrasound (CEUS) perfusion signal in order to produce meaningful imaging markers with the goal of developing a machine-learning model that can classify perfusion curves as benign or malignant in breast cancer data. Twenty-five patients with high suspicion of breast cancer were analyzed with exponentially modified Gaussian (EMG) and gamma variate functions (GVF). The adjusted R2 metric was the criterion for assessing model performance. Various classifiers were trained on the quantified perfusion curves in order to classify the curves as benign or malignant on a voxel basis. Sensitivity, specificity, geometric mean, and AUROC were the validation metrics. The best quantification model was EMG with an adjusted R2 of 0.60 ± 0.26 compared to 0.56 ± 0.25 for GVF. Logistic regression was the classifier with the highest performance (sensitivity, specificity, Gmean, and AUROC = 89.2 ± 10.7, 70.0 ± 18.5, 77.1 ± 8.6, and 91.0 ± 6.6, respectively). This classification method obtained similar results that are consistent with the current literature. Breast cancer patients can benefit from early detection and characterization prior to biopsy. [ABSTRACT FROM AUTHOR]

Abstract: The early detection of breast cancer greatly improves prognosis. One of the earliest signs of cancer is the formation of clusters of microcalcifications. We introduce a novel method for microcalcification detection based on a biologically inspired adaptive model of contrast detection. This model is used in conjunction with image filtering based on anisotropic diffusion and curvilinear structure removal using local energy and phase congruency. An important practical issue in automatic detection methods is the selection of parameters: we show that the parameter values for our algorithm can be estimated automatically from the image. This way, the method is made robust and essentially free of parameter tuning. We report results on mammograms from two databases and show that the detection performance can be improved by first including a normalisation scheme. [Copyright &y& Elsevier]

We present an image analysis method that can detect and measure breast density from digitised mammograms. We present initial results on applying our method to characterise breast changes, in particular, changes due to Hormone Replacement Therapy (HRT). It has been established that long-term use of certain hormone replacement therapies can increase the risk of breast cancer, a fact that encourages the notion that objective measures of tissue density can be an important development in breast cancer image analysis. A set of 59 temporal pairs of mammograms of patients undergoing HRT (two images per patient) were used. The clinician’s assessment of density changes constituted the ground truth for evaluating the proposed quantitative measures of density change. The measures we developed are based on the Standard Mammogram Form (SMF) representation of interesting tissue and their performance (agreement with the expert’s description) is also compared to the “interactive thresholding” method that has been used in the past to characterise mammographic density. The results clearly indicate that present methods for measuring mammographic density fail to characterise temporal changes while the proposed measures have the potential to aid the radiologist in assessing temporal density changes both on a global and a local basis. [Copyright &y& Elsevier]

Increasing use is being made of Gd-DTPA contrast-enhanced magnetic resonance imaging for breast cancer assessment since it provides 3D functional information via pharmacokinetic interaction between contrast agent and tumour vascularity, and because it is applicable to women of all ages as well as patients with post-operative scarring. Contrast-enhanced MRI (CE-MRI) is complementary to conventional X-ray mammography, since it is a relatively low-resolution functional counterpart of a comparatively high-resolution 2D structural representation. However, despite the additional information provided by MRI, mammography is still an extremely important diagnostic imaging modality, particularly for several common conditions such as ductal carcinoma in situ (DCIS) where it has been shown that there is a strong correlation between microcalcification clusters and malignancy. Pathological indicators such as calcifications and fine spiculations are not visible in CE-MRI and therefore there is clinical and diagnostic value in fusing the high-resolution structural information available from mammography with the functional data acquired from MRI imaging. This paper presents a novel data fusion technique whereby medial–lateral oblique (MLO) and cranial–caudal (CC) mammograms (2D data) are registered to 3D contrast-enhanced MRI volumes. We utilise a combination of pharmacokinetic modelling, projection geometry, wavelet-based landmark detection and thin-plate spline non-rigid ‘warping’ to transform the coordinates of regions of interest (ROIs) from the 2D mammograms to the spatial reference frame of the contrast-enhanced MRI volume. Of key importance is the use of a flexible wavelet-based feature extraction technique that enables feature correspondences to be robustly determined between the very different image characteristics of X-ray mammography and MRI. An evaluation of the fusion framework is demonstrated with a series of clinical cases and a total of 14 patient examples. [Copyright &y& Elsevier]

Abstract Accumulating evidence during the last decades revealed that androgens exert membrane-initiated actions leading to the modulation of significant cellular processes, important for cancer cell growth and metastasis (including prostate and breast), that involve signaling via specific kinases. Collectively, many nonclassical, cell surface-initiated androgen actions are mediated by novel membrane androgen receptors (mARs), unrelated to nuclear androgen receptors. Recently, our group identified the G protein coupled oxo-eicosanoid receptor 1 (OXER1) (a receptor of the arachidonic acid metabolite, 5-oxoeicosatetraenoic acid, 5-oxoETE) as a novel mAR involved in the rapid effects of androgens. However, two other membrane proteins, G protein-coupled receptor family C group 6 member A (GPRC6A) and zinc transporter member 9 (ZIP9) have also been portrayed as mARs, related to the extranuclear action of androgens. In the present work, we present a comparative study of in silico pharmacology, gene expression and immunocytochemical data of the three receptors in various prostate and breast cancer cell lines. Furthermore, we analyzed the immunohistochemical expression of these receptors in human tumor and non-tumoral specimens and provide a pattern of expression and intracellular distribution. [ABSTRACT FROM AUTHOR]