- Predictive significance of an optimized panel for basal-like breast cancer: Results from the Canadian Cancer Trials Group MA.5 and MA.12 phase III clinical trialsby Karama Asleh on 2021-10-07
CONCLUSIONS: The nestin/INPP4B immunohistochemical panel identifies women with basal breast cancers who benefit from non-anthracycline chemotherapy but not endocrine adjuvant treatments.
- B3GAT3-related linkeropathy and an in-frame homozygous deletion in an adult patientby Anneli C S Bolund on 2021-09-19
CONCLUSION: This is the first report to describe homozygosity for this specific in-frame deletion in B3GAT3 (p.(Leu21del)). We present a young adult phenotype and a summary of previous reported patients with other biallelic B3GAT3-variants for comparison. Previously described patients of B3GAT3-deficiency were, however, all children with phenotypes ranging from prenatal manifestation and early lethality to less severe. We suggest that this novel homozygous in-frame deletion in B3GAT3 may be the...
- Proteomics-derived basal biomarker DNA-PKcs is associated with intrinsic subtype and long-term clinical outcomes in breast cancerby Karama Asleh on 2021-09-10
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...
- Response to Zhang and Yangby Torsten O Nielsen on 2021-05-18
- Synovial Sarcoma Oncogenesis Revealed by Single-Cell Profilingby Alvin Qiu on 2021-04-24
Synovial sarcoma is a soft tissue malignancy driven by the SS18-SSX fusion oncoprotein. In Nature Medicine, Jerby-Arnon et al. present a single-cell dataset for synovial sarcoma that reveals a novel 'core oncogenic program' driven by SS18-SSX, with implications for treatment strategies based on epigenetics, cell-cycle control, and immune augmentation.
- Granulocyte Colony Stimulating Factor Expression in Breast Cancer and Its Association with Carbonic Anhydrase IX and Immune Checkpointsby Shawn C Chafe on 2021-04-03
CONCLUSIONS: The prognostic associations linking G-CSF to immune biomarkers and CAIX strongly support their immunomodulatory roles in the tumour microenvironment.
- A clinical calculator to predict disease outcomes in women with triple-negative breast cancerby Mei-Yin C Polley on 2021-01-03
CONCLUSIONS: This TNBC clinical calculator can be used to predict patient outcomes and may aid physician's communication with TNBC patients regarding their long-term disease outlook and planning treatment strategies.
- Assessment of Ki67 in Breast Cancer: Updated Recommendations From the International Ki67 in Breast Cancer Working Groupby Torsten O Nielsen on 2020-12-28
Ki67 immunohistochemistry (IHC), commonly used as a proliferation marker in breast cancer, has limited value for treatment decisions due to questionable analytical validity. The International Ki67 in Breast Cancer Working Group (IKWG) consensus meeting, held in October 2019, assessed the current evidence for Ki67 IHC analytical validity and clinical utility in breast cancer, including the series of scoring studies the IKWG conducted on centrally stained tissues. Consensus observations and...
- A Rapid and Cost-Effective Gene Expression Assay for the Diagnosis of Well-Differentiated and Dedifferentiated Liposarcomasby Xiu Q Wang on 2020-12-21
Histologic examination neither reliably distinguishes benign lipomas from atypical lipomatous tumor/well-differentiated liposarcoma, nor dedifferentiated liposarcoma from other pleomorphic sarcomas, entities with different prognoses and management. Molecular confirmation of pathognomonic 12q13-15 amplifications leading to MDM2 overexpression is a diagnostic gold standard. Currently the most commonly used assay for this purpose is fluorescence in situ hybridization (FISH), but this is labor...
- Sarcomas: Immune biomarker expression and checkpoint inhibitor trialsby Mayanne M T Zhu on 2020-11-01
Sarcomas are a heterogenous group of mesenchymal cancers comprising over 100 subtypes. Current chemotherapy for all but a very few subtypes has limited efficacy, resulting in 5-year relative survival rates of 16% for metastatic patients. While sarcomas have often been regarded as an "immune cold" tumor category, recent biomarker studies have confirmed a great deal of immune heterogeneity across sarcoma subtypes. Reports from the first generation of clinical trials treating sarcomas with...
- The epigenomics of sarcomaby Benjamin A Nacev on 2020-08-13
Epigenetic regulation is critical to physiological control of development, cell fate, cell proliferation, genomic integrity and, fundamentally, transcriptional regulation. This epigenetic control occurs at multiple levels including through DNA methylation, histone modification, nucleosome remodelling and modulation of the 3D chromatin structure. Alterations in genes that encode chromatin regulators are common among mesenchymal neoplasms, a collection of more than 160 tumour types including over...
- Differential expression and prognostic relevance of autophagy-related markers ATG4B, GABARAP, and LC3B in breast cancerby Svetlana Bortnik on 2020-07-21
CONCLUSIONS: ATG4B levels varied across breast cancer subtypes but did not show prognostic significance. High LC3B expression and high GABARAP expression were both associated with poor prognosis and with clinicopathological characteristics of aggressive disease phenotypes in all breast cancer subtypes.
- Correction to: Mismatch repair protein loss in breast cancer: clinicopathological associations in a large British Columbia cohortby Angela S Cheng on 2020-06-22
In the original publication of the article, the funding statement was published incompletely. The corrected funding statement should read as below.
- Phospho-Ser784-VCP Is Required for DNA Damage Response and Is Associated with Poor Prognosis of Chemotherapy-Treated Breast Cancerby Cuige Zhu on 2020-06-11
Spatiotemporal protein reorganization at DNA damage sites induced by genotoxic chemotherapies is crucial for DNA damage response (DDR), which influences treatment response by directing cancer cell fate. This process is orchestrated by valosin-containing protein (VCP), an AAA+ ATPase that extracts polyubiquinated chromatin proteins and facilitates their turnover. However, because of the essential and pleiotropic effects of VCP in global proteostasis, it remains challenging practically to...
- Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trialsby Jan Hudeček on 2020-05-22
Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that...