Biological Subtypes of Triple-Negative Breast Cancer

Hubalek, Michael; Czech, Theresa; Müller, Hannes M.

doi:10.1159/000455820

Cited by 97 publications

(90 citation statements)

References 59 publications

(71 reference statements)

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“…Eleven samples were excluded from analysis because they did not meet the basal-like score threshold defined in the preanalytical testing. The observation that not all TNBC tumors will be classified into the basal-like subtype based on gene expression is consistent with prior studies that report the presence of luminal androgen receptor subtype tumors and HER2-enriched subtype tumors among TNBCs (59,60). The remaining 45 samples were analyzed for MHCII and TIL gene expression.…”

Section: Validation Of the Mhcii Immune Activation Assay In An Indepesupporting

confidence: 81%

A Multigene Assay Determines Risk of Recurrence in Patients with Triple-Negative Breast Cancer

et al. 2019

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Approximately 40% of patients with stage I-III triple-negative breast cancer (TNBC) recur after standard treatment, whereas the remaining 60% experience long-term disease-free survival (DFS). There are currently no clinical tests to assess the risk of recurrence in TNBC patients. We previously determined that TNBC patients with MHC class II (MHCII) pathway expression in their tumors experienced significantly longer DFS. To translate this discovery into a clinical test, we developed an MHCII Immune Activation assay, which measures expression of 36 genes using NanoString technology. Preanalytical testing confirmed that the assay is accurate and reproducible in formalin-fixed paraffin-embedded (FFPE) tumor specimens. The assay measurements were concordant with RNA-seq, MHCII protein expression, and tumor-infiltrating lymphocyte counts. In a training set of 44 primary TNBC tumors, the MHCII Immune Activation Score was significantly associated with longer DFS (HR ¼ 0.17; P ¼ 0.015). In an independent validation cohort of 56 primary FFPE TNBC tumors, the Immune Activation Score was significantly associated with longer DFS (HR ¼ 0.19; P ¼ 0.011) independent of clinical stage. An Immune Activation Score threshold for identifying patients with very low risk of relapse in the training set provided 100% specificity in the validation cohort. The assay format enables adoption as a standardized clinical prognostic test for identifying TNBC patients with a low risk of recurrence. Correlative data support future studies to determine if the assay can identify patients in whom chemotherapy can be safely deescalated and patients likely to respond to immunotherapy.Significance: The MHCII Immune Activation assay identifies TNBC patients with a low risk of recurrence, addressing a critical need for prognostic biomarker tests that enable precision medicine for TNBC patients.

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Section: Validation Of the Mhcii Immune Activation Assay In An Indepesupporting

confidence: 81%

A Multigene Assay Determines Risk of Recurrence in Patients with Triple-Negative Breast Cancer

et al. 2019

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“…There is still controversy if hereditary BRCA1/2 mutation related tumors represent a separate phenotypic identity. Both TNBC and HGSOC represent heterogenous groups of cancers and recently both tumor types were subdivided into several subtypes [12,14,16,[23][24][25][26][27]. Six subtypes of TNBC (IM, BL1, BL2, LAR, M and MSL) were identified from clustering of gene expression data [12].…”

Section: Brca1/2 Germline Mutation Related Breast and Ovarian Cancersmentioning

confidence: 99%

An immune-centric exploration of BRCA1 and BRCA2 germline mutation related breast and ovarian cancers

et al. 2020

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Background: BRCA1/2 germline mutation related cancers are candidates for new immune therapeutic interventions. This study was a hypothesis generating exploration of genomic data collected at diagnosis for 19 patients. The prominent tumor mutation burden (TMB) in hereditary breast and ovarian cancers in this cohort was not correlated with high global immune activity in their microenvironments. More information is needed about the relationship between genomic instability, phenotypes and immune microenvironments of these hereditary tumors in order to find appropriate markers of immune activity and the most effective anticancer immune strategies. Methods: Mining and statistical analyses of the original DNA and RNA sequencing data and The Cancer Genome Atlas data were performed. To interpret the data, we have used published literature and web available resources such as Gene Ontology, The Cancer immunome Atlas and the Cancer Research Institute iAtlas. Results: We found that BRCA1/2 germline related breast and ovarian cancers do not represent a unique phenotypic identity, but they express a range of phenotypes similar to sporadic cancers. All breast and ovarian BRCA1/2 related tumors are characterized by high homologous recombination deficiency (HRD) and low aneuploidy. Interestingly, all sporadic high grade serous ovarian cancers (HGSOC) and most of the subtypes of triple negative breast cancers (TNBC) also express a high degree of HRD. Conclusions: TMB is not associated with the magnitude of the immune response in hereditary BRCA1/2 related breast and ovarian cancers or in sporadic TNBC and sporadic HGSOC. Hereditary tumors express phenotypes as heterogenous as sporadic tumors with various degree of "BRCAness" and various characteristics of the immune microenvironments. The subtyping criteria developed for sporadic tumors can be applied for the classification of hereditary tumors and possibly also characterization of their immune microenvironment. A high HRD score may be a good candidate biomarker for response to platinum, and potentially PARP-inhibition. Trial registration: Phase I Study of the Oral PI3kinase Inhibitor BKM120 or BYL719 and the Oral PARP Inhibitor Olaparib in Patients With Recurrent TNBC or HGSOC (NCT01623349), first posted on June 20, 2012. The design and the outcome of the clinical trial is not in the scope of this study.

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“…1 The triple negative breast cancer cells lack of expression of estrogen (ER), progesterone (PR) and human epidermal growth factor 2 (HER 2) receptors on cell surface. 2 TNBC has a propensity to propagate to various visceral organs including the liver and lung. 3 Due to the absence of the receptors, the cancer cells do not react to either endocrine or HER-2 targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

α-Santalol functionalized chitosan nanoparticles as efficient inhibitors of polo-like kinase in triple negative breast cancer

et al. 2020

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Biological Subtypes of Triple-Negative Breast Cancer

Cited by 97 publications

References 59 publications

A Multigene Assay Determines Risk of Recurrence in Patients with Triple-Negative Breast Cancer

A Multigene Assay Determines Risk of Recurrence in Patients with Triple-Negative Breast Cancer

An immune-centric exploration of BRCA1 and BRCA2 germline mutation related breast and ovarian cancers

α-Santalol functionalized chitosan nanoparticles as efficient inhibitors of polo-like kinase in triple negative breast cancer

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