Tumor heterogeneity and the unclear metastasis mechanisms are the leading cause for the unavailability of effective targeted therapy for Triple-negative breast cancer (TNBC), a breast cancer (BrCa) subtype characterized by high mortality and high frequency of distant metastasis cases. The identification of prognostic biomarker can improve prognosis and personalized treatment regimes. Herein, we collected gene expression datasets representing TNBC and Non-TNBC BrCa. From the complete dataset, a subset reflecting solely known cancer driver genes was also constructed. Recursive Feature Elimination (RFE) was employed to identify top 20, 25, 30, 35, 40, 45, and 50 gene signatures that differentiate TNBC from the other BrCa subtypes. Five machine learning algorithms were employed on these selected features and on the basis of model performance evaluation, it was found that for the complete and driver dataset, XGBoost performs the best for a subset of 25 and 20 genes, respectively. Out of these 45 genes from the two datasets, 34 genes were found to be differentially regulated. The Kaplan-Meier (KM) analysis for Distant Metastasis Free Survival (DMFS) of these 34 differentially regulated genes revealed four genes, out of which two are novel that could be potential prognostic genes (POU2AF1 and S100B). Finally, interactome and pathway enrichment analyses were carried out to investigate the functional role of the identified potential prognostic genes in TNBC. These genes are associated with MAPK, PI3-AkT, Wnt, TGF-β, and other signal transduction pathways, pivotal in metastasis cascade. These gene signatures can provide novel molecular-level insights into metastasis.

This is a case of recurrent intravascular leiomyomatosis in a pre-menopausal woman of African-Caribbean heritage. She presented in 2006 with multiple uterine leiomyomata, tumour invading the inferior vena cava (IVC) extending into the right atrium, and pulmonary metastases. Her initial presentation was treated surgically. On recurrence she was treated by oestrogen suppression using a combination of goserelin and letrozole, with a substantial response. She subsequently reported further regression of disease following exposure to strong sunlight enabling her to discontinue oestrogen suppression without relapse. The hypothesis is that the benefit was due to vitamin D. The role of hypovitaminosis D in the pathogenesis of uterine leiomyomata is discussed, including epidemiology data demonstrating a link between ethnicity and risk and the proven mechanisms by which vitamin D controls oestrogen and progesterone receptor expression and influences other signalling pathways involved in the pathogenesis of leiomyomas. Data indicating the intermediate malignancy nature of intravascular leiomyomatosis, are discussed. We are not aware of other reports indicating a link between intravascular leiomyomatosis and a lack of vitamin D.

•Optimum management of locally advanced breast cancer is multidisciplinary.•Neoadjuvant chemotherapy is mainstay of management.•Primary surgical treatment may be acceptable in selected patients.