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.

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Background: Androgen receptor (AR) has emerged as a significant favorable prognostic indicator in estrogen receptor expressing (ER +) breast cancer (BCa); however, its clinical and biological relevance in triple negative breast cancer (TNBC) and association with cancer stem cell (CSC) markers remain ambiguous. Methods: We examined the immunohistochemical expression of AR in a cohort of stage I-III TNBC cases (n = 197) with a long-term clinical follow-up data (mean follow-up = 53.6 months). Significance of AR expression was correlated with prognostic biomarkers including cancer stem cell markers (CD44, CD24, and ALDH1), basal markers (CK5, CK14, and nestin), proliferation marker (ki-67), apoptotic marker (Bcl-2), and COX-2. Expression of CK5 and nestin was used for the categorization of TNBC into basal (TN, CK5 + , and/or nestin +) and non-basal (TN, CK5 − , and/or nestin −) phenotypes, and Kaplan-Meier curves were used for estimation of overall survival and breast cancer-specific survival (BCSS). Results: AR expression was observed in 18.8% of non-metastatic TNBC tumors. Expression of AR correlated with lower grade (P < 0.001) and conferred a favorable prognostic significance in patients with axillary lymph node metastasis (P = 0.005). Lack of AR expression correlated with expression of CSC phenotype (CD44 + /CD24 −) (P < 0.001), COX-2 (P = 0.02), basal markers (CK5: P = 0.03), and nestin (P = 0.01). Basal-like phenotype (TN, CK5 + , and/or nestin +) correlated with quadruple-negative breast cancer (QNBC) and showed a significant association with adverse prognostic markers including high proliferation index (P < 0.001), expression of COX-2 (P = 0.009), and CSC phenotype (CD44 + /CD24 − : P = 0.01). Expression of AR remained an independent prognostic indicator for improved overall survival (P = 0.003), whereas basal-like phenotype was associated with an adverse BCSS (P = 0.013). Conclusions: Assessment of AR and basal markers identified biologically and clinically distinct subgroups of TNBC. Expression of AR defined a low-risk TNBC subgroup associated with improved overall survival, whereas expression of basal markers Riaz et al. Androgen Receptor Expression in TNBC (CK5 and nestin) identified a high-risk subgroup associated with adverse BCSS. Integration of immunohistochemical analysis of AR and basal biomarkers to the assessment of TNBC tumors is expected to improve the prognostication of an otherwise heterogeneous disease.

Diffuse large B-cell lymphoma is the commonest type of primary non Hodgkin's lymphoma of bone in the Pakistani population. It is common in all ages. The sites most often involved are femur followed by hip bone. Primary non Hodgkin's lymphoma of bone appears to be more common in males. Our results are comparable to international data with various studies also showing that diffuse large B cell non Hodgkin lymphoma is the commonest primary bone lymphoma. However, primary Bone Lymphoma is more common in children and young adults.