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As the field of translational ‘omics has progressed, refined classifiers at both genomic and proteomic levels have emerged to decipher the heterogeneity of breast cancer in a clinically-applicable way. The integration of ‘omics knowledge at the DNA, RNA and protein levels is further expanding biologic understanding of breast cancer and opportunities for customized treatment, a particularly pressing need in clinically triple negative tumors. For this group of aggressive breast cancers, work from multiple groups has now validated at least four major biologically and clinically distinct omics-based subtypes. While to date most clinical trial designs have considered triple negative breast cancers as a single group, with an expanding arsenal of targeted therapies applicable to distinct biological pathways, survival benefits may be best realized by designing and analyzing clinical trials in the context of major molecular subtypes. While RNA-based classifiers are the most developed, proteomic classifiers proposed for triple negative breast cancer based on new technologies have the potential to more directly identify the most clinically-relevant biomarkers and therapeutic targets. Phospho-proteomic data further identify targetable signalling pathways in a unique subtype-specific manner. Single cell profiling of the tumor microenvironment represents a promising way to allow a better characterization of the heterogeneity of triple negative breast cancer which could be integrated in a spatially resolved context to build an ecosystem-based patient classification. Multi-omic data further allows in silico analysis of genetic and pharmacologic screens to map therapeutic vulnerabilities in a subtype-specific context. This review describes current knowledge about molecular subtyping of triple negative breast cancer, recent advances in omics-based genomics and proteomics diagnostics addressing the diversity of this disease, key advances made through single cell analysis approaches, and developments in treatments including targeted therapeutics being tested in major clinical trials.

Background Extracellular vesicles (EVs) are emerging as non-invasive biomarkers in cancer, but their role in monitoring the response to neoadjuvant systemic treatment (NST) in patients with breast cancer remains unclear. This study aimed to assess whether EV concentration and surface marker profiles in plasma reflect treatment response and clinical outcome in patients with early-stage breast cancer receiving NST. Methods Plasma samples were collected from 59 patients with luminal B-like, HER2-positive, or triple-negative breast cancer before and after NST. EVs were isolated by size exclusion chromatography and characterized by nanoparticle tracking analysis, electron microscopy, Western blotting, and MACSPlex surface marker profiling. Paired samples were available for 29 patients, allowing longitudinal analysis. Results Patients who achieved pathological complete response (pCR) had significantly lower baseline EV concentrations than those with residual disease. Post-treatment EV levels were also lower in patients who remained free from distant metastasis and had improved breast cancer-specific survival. EV surface marker profiling revealed that CD69, CD29, and CD49e were reduced after NST, whereas CD44 was increased. Notably, EpCAM levels increased specifically in non-PCR patients, suggesting persistent tumor-derived EV release, whereas SSEA-4 levels increased only in patients who achieved pCR. Although EV concentrations and markers differed by subtype and outcome, changes in EV levels following NST were not independently predictive of prognosis. Conclusions These findings support the potential of plasma-derived EVs as dynamic biomarkers of treatment response, and suggest possible prognostic relevance in breast cancer. Validation in larger, independent cohorts is needed to assess their clinical applicability.

Precise biomarkers are needed to guide better diagnostics and therapeutics for basal-like breast cancer, for which DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has been recently reported by the Clinical Proteomic Tumor Analysis Consortium as the most specific biomarker. We evaluated DNA-PKcs expression in clinically-annotated breast cancer tissue microarrays and correlated results with immune biomarkers (training set: n  = 300; validation set: n  = 2401). Following a pre-specified study design per REMARK criteria, we found that high expression of DNA-PKcs was significantly associated with stromal and CD8 + tumor infiltrating lymphocytes. Within the basal-like subtype, tumors with low DNA-PKcs and high tumor-infiltrating lymphocytes displayed the most favourable survival. DNA-PKcs expression by immunohistochemistry identified estrogen receptor-positive cases with a basal-like gene expression subtype. Non-silent mutations in PRKDC were significantly associated with poor outcomes. Integrating DNA-PKcs expression with validated immune biomarkers could guide patient selection for DNA-PKcs targeting strategies, DNA-damaging agents, and their combination with an immune-checkpoint blockade.

Adjuvant whole breast irradiation after breast-conserving surgery is a well-established treatment standard for early invasive breast cancer. Screening, early diagnosis, refinement in surgical techniques, the knowledge of new and specific molecular prognostic factors, and now the standard use of more effective neo/adjuvant systemic therapies have proven instrumental in reducing the rates of locoregional relapses. This underscores the need for reliably identifying women with such low-risk disease burdens in whom elimination of radiation from the treatment plan would not compromise oncological safety. This review summarizes the current evidence for radiation de-intensification strategies and details ongoing prospective clinical trials investigating the omission of adjuvant whole breast irradiation in molecularly defined low-risk breast cancers and related evidence supporting the potential for radiation de-escalation in HER2+ and triple-negative clinical subtypes. Furthermore, we discuss the current evidence for the de-escalation of regional nodal irradiation after neoadjuvant chemotherapy. Finally, we also detail the current knowledge of the clinical value of stromal tumor-infiltrating lymphocytes and liquid-based biomarkers as prognostic factors for locoregional relapse.

Antibacterial activity of four traditionally used medicinal plants viz. Zingiber officinale Allium sativum Mentha spicata and Ocimum basilicum have been studied against fish bacterial pathogens using agar disc diffusion method. Bacterial pathogens including Shigella flexneri Enterobacter amnigenus Salmonella typhimurium and Serratia odorifera were isolated from spoiled Rita rita and Schizothorax plagiostomus. Ethanolic and methanolic extracts of naturally dried A. sativum and Z. officinale significantly inhibited the growth of S. typhimurium S. flexneri and E. amnigenus. Additionally all extracts of O. basilicum substantiated moderate inhibition of all tested pathogens whereas ethanolic diethyl ether and chloroform extracts of M. spicata corroborated low effect against all pathogens except S. flexneri. Honey also inhibited growth of S. odorifera E. amnigenus and S. flexneri. Activity index analysis showed the potential use of these plants and honey against S. flexneri when compared to antibiotics. All extracts of medicinal plants also indicated the significant antioxidant activity. The present study shows that these traditional medicinal plants and honey could potentially be used as antibacterial and antioxidant agents.

Background Although most melanomas develop de novo, about 30% are nevus-associated melanomas, where the prognostic value is unclear. Our study aimed to determine whether nevus-associated melanoma is associated with sentinel lymph node (SLN) status and prognosis in patients with melanoma. Methods The Sentinel Lymph Node Working Group database, which includes comprehensive clinicopathological and outcome data, was utilized to investigate the association of nevus-associated melanoma with SLN status as well as relapse-free (RFS), melanoma-specific (MSS), and overall survival (OS) using multivariable logistic regression and Cox regression modeling. Results A total of 3447 adult patients with a median follow-up of 2.6 years (interquartile range 0.9–6.9) were evaluable. Compared with de novo melanomas, nevus-associated melanomas showed a significant correlation with younger age as well as favorable histological features. The presence of a nevus-associated melanoma was not identified as an independent factor for SLN status (odds ratio 1.06, 95% confidence interval [CI] 0.80–1.41; p  = 0.68). Compared with de novo melanomas, nevus-associated melanomas provided independent prognostic information for a favorable RFS (hazard ratio [HR] 0.67, 95% CI 0.53–0.84; p  < 0.001), MSS (HR 0.54, 95% CI 0.34–0.85; p  = 0.008), and OS (HR 0.42, 95% CI 0.30–0.57; p  < 0.001). Conclusion Melanomas associated with pre-existing nevi appear to be an independent favorable prognostic factor for recurrence and survival and may potentially be used as a clinical parameter for identifying patients with lower risk of recurrence.

Colony-stimulating factor-1 receptor (CSF-1R) signaling promotes an immune suppressive microenvironment enriched in M2 macrophages. Given that CSF-1R inhibitors are under investigation in clinical trials, including in breast cancer, CSF-1R expression and association with immune biomarkers could identify patients who derive greater benefit from combination with immunotherapies. TIMER2.0 and bc-GenExMiner v4.7 were used to assess the correlation of CSF1R mRNA with immune infiltrates and prognosis. Following a prespecified training–validation approach, an optimized immunohistochemistry assay was applied to assess CSF-1R on carcinoma cells and macrophages on breast cancer tissue microarray series representing 2384 patients, coupled to comprehensive clinicopathological, biomarker, and outcome data. Significant positive correlations were observed between CSF1R mRNA and immune infiltrates. High carcinoma CSF-1R correlated with grade 3 tumors >2 cm, hormone receptor negativity, high Ki67, immune checkpoint biomarkers, and macrophages expressing CSF-1R and CD163. High carcinoma CSF-1R was significantly associated with poor survival in univariate and multivariate analyses. Adverse prognostic associations were retained in ER+ cases regardless of the presence of CD8+ T cells. CSF-1R+ macrophages were not prognostic. High carcinoma CSF-1R is associated with aggressive breast cancer biology and poor prognosis, particularly in ER+ cases, and identifies patients in whom biomarker-directed CSF-1R therapies may yield superior therapeutic responses.