Heterogeneity Within Molecular Subtypes of Breast Cancer

2021 ◽  
Author(s):  
Kevin M. Turner ◽  
Syn Kok Yeo ◽  
Tammy M Holm ◽  
Elizabeth Shaughnessy ◽  
Jun-Lin Guan
Keyword(s):  
Breast Cancer ◽  
Molecular Subtypes ◽  
Tumor Biology ◽  
Treatment Resistance ◽  
Intratumoral Heterogeneity ◽  
Molecular Heterogeneity ◽  
Improve Treatment ◽  
Therapeutic Decisions ◽  
Single Tumor

Breast cancer is the quintessential example of how molecular characterization of tumor biology guides therapeutic decisions. From the discovery of the estrogen receptor to current clinical molecular profiles to evolving single cell analytics, the characterization and compartmentalization of breast cancer into divergent subtypes is clear. However, competing with this divergent model of breast cancer is the recognition of intratumoral heterogeneity, which acknowledges the possibility that multiple different subtypes exist within a single tumor. Intratumoral heterogeneity is driven by both intrinsic effects of the tumor cells themselves as well as extrinsic effects from the surrounding microenvironment. There is emerging evidence that these intratumoral molecular subtypes are not static; rather, plasticity between divergent subtypes is possible. Inter-conversion between seemingly different subtypes within a tumor drives tumor progression, metastases, and treatment resistance. Therapeutic strategies must therefore contend with changing phenotypes in an individual patient's tumor. Identifying targetable drivers of molecular heterogeneity may improve treatment durability and disease progression.

scholarly journals The Many Facets of Tumor Heterogeneity: Is Metabolism Lagging Behind?

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1574 ◽  
Author(s):  
Sara Loponte ◽  
Sara Lovisa ◽  
Angela K. Deem ◽  
Alessandro Carugo ◽  
Andrea Viale
Keyword(s):  
Tumor Biology ◽  
Tumor Development ◽  
Treatment Resistance ◽  
Intratumoral Heterogeneity ◽  
Functional Heterogeneity ◽  
Extrinsic Factors ◽  
Metabolic Heterogeneity ◽  
The Many ◽  
Metabolic Strategies

Tumor functional heterogeneity has been recognized for decades, and technological advancements are fueling renewed interest in uncovering the cell-intrinsic and extrinsic factors that influence tumor development and therapeutic response. Intratumoral heterogeneity is now arguably one of the most-studied topics in tumor biology, leading to the discovery of new paradigms and reinterpretation of old ones, as we aim to understand the profound implications that genomic, epigenomic, and functional heterogeneity hold with regard to clinical outcomes. In spite of our improved understanding of the biological complexity of cancer, characterization of tumor metabolic heterogeneity has lagged behind, lost in a century-old controversy debating whether glycolysis or mitochondrial respiration is more influential. But is tumor metabolism really so simple? Here, we review historical and current views of intratumoral heterogeneity, with an emphasis on summarizing the emerging data that begin to illuminate just how vast the spectrum of metabolic strategies a tumor can employ may be, and what this means for how we might interpret other tumor characteristics, such as mutational landscape, contribution of microenvironmental influences, and treatment resistance.

Radiomics- Quantitative Biomarker Analysis for Breast Cancer Diagnosis and Prediction: A Review

2021 ◽  
Vol 17 ◽  
Author(s):  
Priscilla Dinkar Moyya ◽  
Mythili Asaithambi
Keyword(s):  
Breast Cancer ◽  
Molecular Subtypes ◽  
Breast Cancer Diagnosis ◽  
Benign Tumors ◽  
Genomic Information ◽  
Tumor Characterization ◽  
Breast Malignancy ◽  
The Past ◽  
Biomarker Analysis

Background: Cancer of the breast has become a global problem for women's health. Though concerns regarding early detection and accurate diagnosis were raised, an effort is required for precision medicine as well as personalized treatment. In the past years, the area of medicinal imaging has seen an unprecedented growth that leads to an advancement of radiomics, which provides countless quantitative biomarkers extracted from modern diagnostic images, including a detailed tumor characterization of breast malignancy. Discussion: In this research, we presented the methodology and implementation of radiomics, together with its future trends and challenges by the basis of published papers. Radiomics could distinguish between malignant from benign tumors, predict prognostic factors, molecular subtypes of breast carcinoma, treatment response to neoadjuvant chemotherapy (NAC), and recurrence survival. The incorporation of quantitative knowledge with clinical, histopathological and genomic information will enable physicians to afford customized care of treatment for patients with breast cancer. Conclusion: Our research was intended to help physicians and radiologists learn fundamental knowledge about radiomics and also to work collaboratively with researchers to explore evidence for further usage in clinical practice.

Breast cancer in Angola, molecular subtypes: The first preliminary study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13075-e13075
Author(s):  
Lúcio Lara Santos ◽  
Fernando Miguel ◽  
Lygia Vieira Lopes ◽  
Julio Oliveira ◽  
Eduardo Ferreira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Locally Advanced ◽  
Luminal A ◽  
Her2 Positive ◽  
Luminal B ◽  
Therapeutic Decisions ◽  
Ihc Markers

e13075 Background: Women in sub-Saharan African countries, as Angola, are experiencing an increasing burden of aggressive breast cancer. Breast cancer molecular subtypes may enable more accurate diagnoses and support therapeutic decisions, however several studies have suggested that African breast cancers are predominantly hormone receptor poor. We conduct a study, to correlate the clinical pathological profiles and molecular subtypes, according its surrogate immunohistochemistry (IHC) markers, of breast cancer in Luanda, Angola. Methods: From Jan. 2011 to Dec. 30, 2014, 179 consecutive cases of microscopically confirmed invasive breast carcinoma that were evaluable for histology and IHC (ER, PR, HER2, and Ki-67) were classified. However, 21.8% (n = 39) of cases were poorly preserved, therefore it was only possible to study IHC in 140 cases. Results: All patients were female, the median age was 47 years (24-84 years). Invasive ductal carcinoma was the most common type, 91.4% (n = 128), grade 2 (moderately differentiated) was prevalent, 67.1%. Most of the tumours were locally advanced, stage III 65% (n = 91) and stage IV 3.6% (n = 5). In 140 cases studied, 53.2% (n = 74 ) of malignancies were hormone receptors positive, whence 25.7% were luminal A like, 19.3% luminal B like/ HER2 negative, 7.9% luminal B like/HER2 positive, 15.7% HER2 positive and 31,4% were triple-negative. Conclusions: Woman with breast cancer in Luanda-Angola were caracterized by advance stage and younger age at diagnosis of disease. The two predominant molecular subtypes are triple negative and luminal A like. Therefore, determining the molecular subtype using surrogate IHC markers has important treatment and prognostic implications for Angola women with breast cancer.

scholarly journals Proteomic Characterization of Serum Small Extracellular Vesicles in Human Breast Cancer

2021 ◽  
Author(s):  
Ganfei Xu ◽  
Weiyi Huang ◽  
Shaoqian Du ◽  
Minjing Huang ◽  
Jiacheng Lyu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Reference Value ◽  
Human Breast ◽  
Serum Samples ◽  
Healthy Donors ◽  
Diagnosis And Classification

There is a lack of comprehensive understanding of breast cancer (BC) specific sEVs characteristics and composition on BC unique proteomic information from human samples. Here, we interrogated the proteomic landscape of sEVs in 167 serum samples from patients with BC, benign mammary disease (BD) and from healthy donors (HD). The analysis provides a comprehensive landscape of serum sEVs with totally 9,589 proteins identified, considerably expanding the panel of sEVs markers. Of note, serum BC-sEVs protein signatures were distinct from those of BD and HD, representing stage- and molecular subtype-specific patterns. We constructed specific sEVs protein identifiers that could serve as a liquid biopsy tool for diagnosis and classification of BC from benign mammary disease, molecular subtypes, as well as assessment of lymph node metastasis. We also identified 11 potential survival biomarkers for distant metastasis. This work may provide reference value for the accurate diagnosis and monitoring of BC progression using serum sEVs.

scholarly journals Hypoxia and serum deprivation induces glycan alterations in triple negative breast cancer cells

2018 ◽  
Vol 399 (7) ◽  
pp. 661-672 ◽  
Author(s):  
Amanda P.B. Albuquerque ◽  
Meritxell Balmaña ◽  
Stefan Mereiter ◽  
Filipe Pinto ◽  
Celso A. Reis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Biology ◽  
Public Health Problem ◽  
Treatment Resistance ◽  
Bioinformatic Analysis ◽  
Serum Deprivation ◽  
Global Public Health ◽  
Advanced Stages

AbstractTriple negative breast cancer (TNBC) is a major global public health problem. The lack of targeted therapy and the elevated mortality evidence the need for better knowledge of the tumor biology. Hypoxia and aberrant glycosylation are associated with advanced stages of malignancy, tumor progression and treatment resistance. Importantly, serum deprivation regulates the invasive phenotype and favors TNBC cell survival. However, in TNBC, the role of hypoxia and serum deprivation in the regulation of glycosylation remains largely unknown. The effects of hypoxia and serum deprivation on the expression of glycosyltransferases and glycan profile were evaluated in the MDA-MB-231 cell line. We showed that the overexpression of HIF-1α was accompanied by acquisition of epithelial-mesenchimal transition features. Significant upregulation of fucosyl- and sialyltransferases involved in the synthesis of tumor-associated carbohydrate antigens was observed together with changes in fucosylation and sialylation detected byAleuria aurantialectin andSambucus nigraagglutinin lectin blots. Bioinformatic analysis further indicated a mechanism by which HIF-1α can regulateST3GAL6expression and the relationship within the intrinsic characteristics of TNBC tumors. In conclusion, our results showed the involvement of hypoxia and serum deprivation in glycosylation profile regulation of TNBC cells triggering breast cancer aggressive features and suggesting glycosylation as a potential diagnostic and therapeutic target.

Intratumoral heterogeneity of the distribution of kinetic parameters in breast cancer: comparison based on the molecular subtypes of invasive breast cancer

Breast Cancer ◽  
2014 ◽  
Vol 22 (5) ◽  
pp. 496-502 ◽  
Author(s):  
Ken Yamaguchi ◽  
Hiroyuki Abe ◽  
Gillian M. Newstead ◽  
Ryoko Egashira ◽  
Takahiko Nakazono ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Kinetic Parameters ◽  
Invasive Breast Cancer ◽  
Molecular Subtypes ◽  
Intratumoral Heterogeneity

scholarly journals A New Challenge for Radiologists: Radiomics in Breast Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Paola Crivelli ◽  
Roberta Eufrasia Ledda ◽  
Nicola Parascandolo ◽  
Alberto Fara ◽  
Daniela Soro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Randomized Clinical Trials ◽  
Molecular Subtypes ◽  
Quantitative Information ◽  
Breast Cancer Patients ◽  
Cochrane Database ◽  
Meta Analyses ◽  
Comprehensive Characterization

Introduction. Over the last decade, the field of medical imaging experienced an exponential growth, leading to the development of radiomics, with which innumerable quantitative features are obtained from digital medical images, providing a comprehensive characterization of the tumor. This review aims to assess the role of this emerging diagnostic tool in breast cancer, focusing on the ability of radiomics to predict malignancy, response to neoadjuvant chemotherapy, prognostic factors, molecular subtypes, and risk of recurrence. Evidence Acquisition. A literature search on PubMed and on Cochrane database websites to retrieve English-written systematic reviews, review articles, meta-analyses, and randomized clinical trials published from August 2013 up to July 2018 was carried out. Results. Twenty papers (19 retrospective and 1 prospective studies) conducted with different conventional imaging modalities were included. Discussion. The integration of quantitative information with clinical, histological, and genomic data could enable clinicians to provide personalized treatments for breast cancer patients. Current limitations of a routinely application of radiomics are represented by the limited knowledge of its basics concepts among radiologists and by the lack of efficient and standardized systems of feature extraction and data sharing.

scholarly journals The prognostic link between metabolic syndrome and the different breast cancer molecular subtypes: a case control study.

2020 ◽  
Author(s):  
Yi zuo Chen ◽  
Yu ying Zhou ◽  
En dong Chen ◽  
Di shuang Hu ◽  
Xuan Shao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metabolic Syndrome ◽  
Molecular Subtypes ◽  
Molecular Heterogeneity ◽  
Luminal A ◽  
Luminal B ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
Her 2

Abstract Background Metabolic syndrome (MetS) is an important factor related to the poor prognosis of breast cancer (BC). Molecular heterogeneity in the tumor may affect the consequence of BC. The main purpose of this study was to assess the prognostic link between MetS and the different BC molecular subtypes. Methods A total of 960 patients with BC were recruited from January 2010 to June 2014. The relationship between MetS and disease prognosis was assessed by using univariate and multivariate analyses. Results At recruitment, MetS was diagnosed in 199 patients (20.7%). The mean follow-up period was 68.5 months (range, 2–103 months). MetS remained significantly associated with 64% increased risk of recurrence (Hazard Ratio (HR)=1.64; 95% confidence interval (CI) 1.19–2.27, P<0.01) and twofold increased risk of mortality (HR=2.02, 95% CI 1.29–3.16, P<0.01) according to multivariate analysis. By reviewing BC molecular subtypes, the significant associations remained in the subsets of Luminal A (HR=3.1, 95% CI 1.28–4.57, P=0.01), Luminal B (Her2-negative) (HR=3.3, 95% CI 1.31–8.33, P=0.01), and Her-2-positive (non-Luminal) (HR=2.2, 95% CI 1.10–4.39, P=0.03). Conclusions MetS was significantly related to unfavorable prognosis in operable BC, especially in the subgroup of Luminal A. More studies are needed to definitively determine which factors influence the association of MetS with Luminal A subtype.

scholarly journals Intratumoral Heterogeneity Promotes Collective Cancer Invasion through NOTCH1 Variation

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3084
Author(s):  
Peter Torab ◽  
Yue Yan ◽  
Mona Ahmed ◽  
Hironobu Yamashita ◽  
Joshua I. Warrick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Interference ◽  
Computational Model ◽  
Poor Prognosis ◽  
Gene Editing ◽  
Molecular Subtypes ◽  
Intratumoral Heterogeneity ◽  
Molecular Heterogeneity ◽  
Agent Based ◽  
And Control

Cellular and molecular heterogeneity within tumors has long been associated with the progression of cancer to an aggressive phenotype and a poor prognosis. However, how such intratumoral heterogeneity contributes to the invasiveness of cancer is largely unknown. Here, using a tumor bioengineering approach, we investigate the interaction between molecular subtypes within bladder microtumors and the corresponding effects on their invasiveness. Our results reveal heterogeneous microtumors formed by multiple molecular subtypes possess enhanced invasiveness compared to individual cells, even when both cells are not invasive individually. To examine the molecular mechanism of intratumoral heterogeneity mediated invasiveness, live single cell biosensing, RNA interference, and CRISPR-Cas9 gene editing approaches were applied to investigate and control the composition of the microtumors. An agent-based computational model was also developed to evaluate the influence of NOTCH1 variation on DLL4 expression within a microtumor. The data indicate that intratumoral variation in NOTCH1 expression can lead to upregulation of DLL4 expression within the microtumor and enhancement of microtumor invasiveness. Overall, our results reveal a novel mechanism of heterogeneity mediated invasiveness through intratumoral variation of gene expression.

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