Insights on Aromatase Immunohistochemistry: Variations between Intrinsic Molecular Subtypes of Breast Cancers

2020 ◽  
Vol 16 (1) ◽  
pp. 17-24
Author(s):  
I Armasu
Keyword(s):  
Molecular Subtypes ◽  
Breast Cancers

scholarly journals Association between levels of tumor-infiltrating lymphocytes in different subtypes of primary breast tumors and prognostic outcomes: a meta-analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Lin He ◽  
Yaling Wang ◽  
Qian Wu ◽  
Yuhua Song ◽  
Xuezhen Ma ◽  
...  
Keyword(s):  
Molecular Subtypes ◽  
Meta Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Breast Tumors ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Tumor Subtype ◽  
Luminal Tumor ◽  
High Level ◽  
Infiltrating Lymphocytes

Abstract Background To investigate the impact of the elevation of tumor-infiltrating lymphocytes (TILs) in different molecular subtypes of primary breast cancer, i.e. each 10% increment of TILs and high-level TILs (TILs≥50%) in tumor, on overall survival (OS) and pathological complete response (pCR) and to compare the presentation of high-level TILs across these molecular subtypes. Methods Citation retrieval was performed in the PubMed, Cochrane Library, Embase and Web of Science databases. All statistical calculations were performed by the software of StataSE version 12.0. Results Twenty-two eligible clinical trials including 15,676 unique patients were included for meta-analysis. Each 10% increment of TILs significantly improved OS in human epidermal growth factor receptor 2 (HER2)-overexpression (pooled Hazard ratio (HR), 0.92; 95% CI, 0.89–0.95) and triple-negative (TN) (pooled HR, 0.90; 95% CI, 0.89–0.92) breast tumors but not in luminal tumor subtype (pooled HR, 1.06; 95% CI, 0.99–1.13). It was also associated with an increased pCR rate in breast cancers (pooled Odds ratio (OR), 1.27; 95% CI, 1.19–13.5). High-level TILs were significantly related with a higher pCR rate (pooled OR, 2.73; 95% CI, 2.40–3.01) than low-level TILs. The HER2-amplified (pooled OR, 3.14; 95% CI, 1.95–5.06) and TN (pooled OR, 4.09; 95% CI, 2.71–6.19) phenotypes of breast cancers expressed significantly more high-level TILs than the luminal tumor subtype, although the presentation of those between the former two subsets was not significantly different (pooled OR, 1.30; 95%CI, 0.83–2.04). Conclusions The elevation of TILs in breast tumors predicts favorable prognostic outcomes, particularly in the HER2-overexpression and TN subtypes.

scholarly journals Characterization of cell lines derived from breast cancers and normal mammary tissues for the study of the intrinsic molecular subtypes

2013 ◽  
Vol 142 (2) ◽  
pp. 237-255 ◽  
Author(s):  
Aleix Prat ◽  
Olga Karginova ◽  
Joel S. Parker ◽  
Cheng Fan ◽  
Xiaping He ◽  
...  
Keyword(s):  
Cell Lines ◽  
Molecular Subtypes ◽  
Breast Cancers ◽  
Mammary Tissues

scholarly journals Single cell transcriptomics reveals molecular subtype and functional heterogeneity in models of breast cancer

2018 ◽  
Author(s):  
Daniel L. Roden ◽  
Laura A. Baker ◽  
Benjamin Elsworth ◽  
Chia-Ling Chan ◽  
Kate Harvey ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Single Cell ◽  
Cell Line ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Cellular Heterogeneity ◽  
Breast Cancers ◽  
Intrinsic Subtypes ◽  
Pdx Model

AbstractBreast cancer has long been classified into a number of molecular subtypes that predict prognosis and therefore influence clinical treatment decisions. Cellular heterogeneity is also evident in breast cancers and plays a key role in the development, evolution and metastatic progression of many cancers. How clinical heterogeneity relates to cellular heterogeneity is poorly understood, so we approached this question using single cell gene expression analysis of well established in vitro and in vivo models of disease.To explore the cellular heterogeneity in breast cancer we first examined a panel of genes that define the PAM50 classifier of molecular subtype. Five breast cancer cell line models (MCF7, BT474, SKBR3, MDA-MB-231, and MDA-MB-468) were selected as representatives of the intrinsic molecular subtypes (luminal A and B, basal-like, and Her2-enriched). Single cell multiplex RT-PCR was used to isolate and quantify the gene expression of single cells from each of these models, and the PAM50 classifier applied. Using this approach, we identified heterogeneity of intrinsic subtypes at single-cell level, indicating that cells with different subtypes exist within a cell line. Using the Chromium 10X system, this study was extended into thousands of cells from the MCF7 cell-line and an ER+ patient derived xenograft (PDX) model and again identified significant intra-tumour heterogeneity of molecular subtype.Estrogen Receptor (ER) is an important driver and therapeutic target in many breast cancers. It is heterogeneously expressed in a proportion of clinical cases but the significance of this to ER activity is unknown. Significant heterogeneity in the transcriptional activation of ER regulated genes was observed within tumours. This differential activation of the ER cistrome aligned with expression of two known transcriptional co-regulatory factors of ER (FOXA1 and PGR).To examine the degree of heterogeneity for other important phenotypic traits, we used an unsupervised clustering approach to identify cellular sub-populations with diverse cancer associated transcriptional properties, such as: proliferation; hypoxia; and treatment resistance. In particular, we show that we can identify two distinct sub-populations of cells that may have denovo resistance to endocrine therapies in a treatment naïve PDX model of ER+ breast cancer. One of these consists of cells with a non-proliferative transcriptional phenotype that is enriched for transcriptional properties of ERBB2 tumours. The other is heavily enriched for components of the primary cilia. Gene regulatory networks were used to identify transcription factor regulons that are active in each cell, leading us to identify potential transcriptional drivers (such as E2F7, MYB and RFX3) of the cilia associated endocrine resistant cells. This rare subpopulation of cells also has a highly heterogenous mix of intrinsic subtypes highlighting a potential role of intra-tumour subtype heterogeneity in endocrine resistance and metastatic potential.Overall, These results suggest a high degree of cellular heterogeneity within breast cancer models, even cell lines, that can be functionally dissected into sub-populations of cells with transcriptional phenotypes of potential clinical relevance.

Impact of molecular subtype on presenting characteristics of T1a,b tumors

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11111-11111
Author(s):  
L. Wiechmann ◽  
L. Jacks ◽  
S. Patil ◽  
M. Stempel ◽  
M. Morrow
Keyword(s):  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Breast Conservation ◽  
Distant Recurrence ◽  
Good Prognosis ◽  
Breast Cancers ◽  
Chi Square ◽  
Prognostic Features ◽  
Small Breast ◽  
The Impact

11111 Background: Gene expression profiling of breast cancers has identified molecular subtypes (Lum A and B, basal, HER2) which impact upon the risk of both local and distant recurrence. There is interest in the impact of molecular subtype on outcome in T1a,bN0M0 tumors, a group thought to have good prognosis and to be amenable to breast conservation. The purpose of this study was to determine if presenting features of T1a,b tumors differ among molecular subtypes. Methods: Subtypes were classified using IHC as Lum A (ER±PR pos, HER2 neg); Lum B: (ER±PR pos, HER2 pos); HER2: (ER+PR neg, HER2 pos); or Basal: ER, PR, and HER2 neg. Data was obtained from a registered database which included patients treated in our institution between 1/98 and 6/07. Of 7906 eligible patients, 6016 were classifiable into molecular subtypes and 1974 tumors (32.8%) measured 10 mm or less. The Chi square test and ANOVA were used for statistical analysis. Results: Data are shown in Table 1 . Patients overexpressing HER2 were significantly younger, had more nodal involvement, multicentric/multifocal (Multi) disease, extensive intraductal component (EIC), and lymphovascular invasion (LVI) (all p<0.0001). On multivariate analysis the HER2 subtype had an odds ratio of 2.5 for Multi versus Lum A/B, but HER 2 was not predictive of nodal status. Conclusions: Even in small breast cancers, presenting features vary with molecular subtype. Unlike Multi, the higher incidence of positive nodes in HER2 patients is explained by traditional prognostic features such as grade, age, and size rather than subtype, suggesting that evaluation of traditional prognostic factors remains valuable in the molecular era. [Table: see text] No significant financial relationships to disclose.

Molecular Subtypes of Breast Cancers Detected in Mammography Screening and Outside of Screening

2008 ◽  
Vol 14 (13) ◽  
pp. 4103-4110 ◽  
Author(s):  
Harri Sihto ◽  
Johan Lundin ◽  
Tiina Lehtimäki ◽  
Maarit Sarlomo-Rikala ◽  
Ralf Bützow ◽  
...  
Keyword(s):  
Mammography Screening ◽  
Molecular Subtypes ◽  
Breast Cancers

scholarly journals BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients

2020 ◽  
Vol 12 ◽  
pp. 175883592097532
Author(s):  
Lorena Incorvaia ◽  
Daniele Fanale ◽  
Marco Bono ◽  
Valentina Calò ◽  
Alessia Fiorino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
University Hospital ◽  
Sequencing Analysis ◽  
Breast Cancers ◽  
Luminal B ◽  
Pathogenic Variants ◽  
Mutational Status ◽  
Phenotypic Features

Background: Several available data suggest the association between specific molecular subtypes and BRCA1/2 mutational status. Previous investigations showed the association between BRCA1/2 pathogenic variants (PVs) in specific genomic regions and phenotypic variations of cancer relative risk, while the role of PV type and location in determining the breast cancer (BC) phenotypic features remains still unclear. The aim of this research was to describe the germline BRCA1/2 PVs in triple-negative breast cancer (TNBC) versus luminal-like BC and their potential leverage on BC phenotype. Patients & methods: We retrospectively collected and analyzed all clinical information of 531 patients with BC genetically tested for germline BRCA1/2 PVs by Next-Generation Sequencing analysis at University Hospital Policlinico “P. Giaccone” of Palermo (Sicily) from January 2016 to February 2020. Results: Our results corroborate the evidence that BRCA1-related tumors often have a profile which resembles the TNBC subtype, whereas BRCA2-associated tumors have a profile that resembles luminal-like BC, especially the Luminal B subtype. Interestingly, our findings suggest that the PVs identified in TNBC were not largely overlapping with those in luminal-like tumors. Differences in the frequency of two PVs potentially associated with different molecular tumor subtypes were observed. BRCA1-633delC was detected with relatively higher prevalence in patients with TNBC, whereas BRCA2-1466delT was found mainly in Luminal B tumors, but in no TNBC patient. Conclusion: Future studies examining the type and location of BRCA1/2 PVs within different molecular subtypes are required to verify our hypothesis and could provide an interesting insight into the complex topic of genotype–phenotype correlations. Additionally, a more in-depth understanding of the potential correlations between BRCA PVs and clinical and phenotypic features of hereditary BC syndrome patients could be the key to develop better strategies of prevention and surveillance in BRCA-positive carriers without disease.

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