Influence of the interaction between nodal fibroblast and breast cancer cells on gene expression

Our aim was to evaluate the interaction between breast cancer cells and nodal fibroblasts, by means of their gene expression profile. Fibroblast primary cultures were established from negative and positive lymph nodes from breast cancer patients and a similar gene expression pattern was identified, following cell culture. Fibroblasts and breast cancer cells (MDA-MB231, MDA-MB435, and MCF7) were cultured alone or co-cultured separated by a porous membrane (which allows passage of soluble factors) for comparison. Each breast cancer lineage exerted a particular effect on fibroblasts viability and transcriptional profile. However, fibroblasts from positive and negative nodes had a parallel transcriptional behavior when co-cultured with a specific breast cancer cell line. The effects of nodal fibroblasts on breast cancer cells were also investigated. MDA MB-231 cells viability and migration were enhanced by the presence of fibroblasts and accordingly, MDA-MB435 and MCF7 cells viability followed a similar pattern. MDA-MB231 gene expression profile, as evaluated by cDNA microarray, was influenced by the fibroblasts presence, and HNMT, COMT, FN3K, and SOD2 were confirmed downregulated in MDA-MB231 co-cultured cells with fibroblasts from both negative and positive nodes, in a new series of RT-PCR assays. In summary, transcriptional changes induced in breast cancer cells by fibroblasts from positive as well as negative nodes are very much alike in a specific lineage. However, fibroblasts effects are distinct in each one of the breast cancer lineages, suggesting that the inter-relationships between stromal and malignant cells are dependent on the intrinsic subtype of the tumor

Social determinants of health and the prediction of missed breast imaging appointments

Abstract Background Predictive models utilizing social determinants of health (SDH), demographic data, and local weather data were trained to predict missed imaging appointments (MIA) among breast imaging patients at the Boston Medical Center (BMC). Patients were characterized by many different variables, including social needs, demographics, imaging utilization, appointment features, and weather conditions on the date of the appointment. Methods This HIPAA compliant retrospective cohort study was IRB approved. Informed consent was waived. After data preprocessing steps, the dataset contained 9,970 patients and 36,606 appointments from 1/1/2015 to 12/31/2019. We identified 57 potentially impactful variables used in the initial prediction model and assessed each patient for MIA. We then developed a parsimonious model via recursive feature elimination, which identified the 25 most predictive variables. We utilized linear and non-linear models including support vector machines (SVM), logistic regression (LR), and random forest (RF) to predict MIA and compared their performance. Results The highest-performing full model is the nonlinear RF, achieving the highest Area Under the ROC Curve (AUC) of 76% and average F1 score of 85%. Models limited to the most predictive variables were able to attain AUC and F1 scores comparable to models with all variables included. The variables most predictive of missed appointments included timing, prior appointment history, referral department of origin, and socioeconomic factors such as household income and access to caregiving services. Conclusions Prediction of MIA with the data available is inherently limited by the complex, multifactorial nature of MIA. However, the algorithms presented achieved acceptable performance and demonstrated that socioeconomic factors were useful predictors of MIA. In contrast with non-modifiable demographic factors, we can address SDH to decrease the incidence of MIA