scholarly journals Survival outcomes are associated with genomic instability in luminal breast cancers

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0245042
Author(s):  
Lydia King ◽  
Andrew Flaus ◽  
Emma Holian ◽  
Aaron Golden
Keyword(s):  
Breast Cancer ◽  
Genomic Instability ◽  
Cancer Survival ◽  
Molecular Taxonomy ◽  
Gene Signature ◽  
Therapeutic Interventions ◽  
Survival Outcomes ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A

Breast cancer is the leading cause of cancer related death among women. Breast cancers are generally diagnosed and treated based on clinical and histopathological features, along with subtype classification determined by the Prosigna Breast Cancer Prognostic Gene Signature Assay (also known as PAM50). Currently the copy number alteration (CNA) landscape of the tumour is not considered. We set out to examine the role of genomic instability (GI) in breast cancer survival since CNAs reflect GI and correlate with survival in other cancers. We focused on the 70% of breast cancers classified as luminal and carried out a comprehensive survival and association analysis using Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data to determine whether CNA Score Quartiles derived from absolute CNA counts are associated with survival. Analysis revealed that patients diagnosed with luminal A breast cancer have a CNA landscape associated with disease specific survival, suggesting that CNA Score can provide a statistically robust prognostic factor. Furthermore, stratification of patients into subtypes based on gene expression has shown that luminal A and B cases overlap, and it is in this region we largely observe luminal A cases with reduced survival outlook. Therefore, luminal A breast cancer patients with quantitatively elevated CNA counts may benefit from more aggressive therapy. This demonstrates how individual genomic landscapes can facilitate personalisation of therapeutic interventions to optimise survival outcomes.

scholarly journals Survival outcomes are associated with genomic instability in luminal breast cancers

2020 ◽  
Author(s):  
Lydia King ◽  
Andrew Flaus ◽  
Aaron Golden
Keyword(s):  
Breast Cancer ◽  
Genomic Instability ◽  
Statistical Tests ◽  
Molecular Taxonomy ◽  
Therapeutic Interventions ◽  
Survival Outcomes ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Grade 3

AbstractBreast cancer is the leading cause of cancer related death among women. Breast cancers are generally diagnosed and treated based on clinical and histopathological features, along with subtype classification determined by the Prosigna Breast Cancer Prognostic Gene Signature Assay (also known as PAM50). Currently the copy number alteration (CNA) landscape of the tumour is not considered. We set out to examine the role of genomic instability (GI) in breast cancer survival since CNAs reflect GI and correlate with survival in other cancers. We focussed on the 70% of breast cancers classified as luminal and carried out a comprehensive survival and association analysis using Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) data to determine whether CNA burden quartiles derived from absolute CNA counts are associated with survival. Luminal A and B patients were stratified by PAM50 subtype and tumour grade and then tested for association with CNA burden using multiple statistical tests. Analysis revealed that patients diagnosed with luminal A grade 3 breast cancer have a CNA landscape associated with disease specific survival, suggesting that these patients could be classified as at-risk. Furthermore, luminal A grade 3 cases largely occupy a region of stratification based on gene expression at the boundary where luminal A and luminal B cases overlap. We conclude that GI reflected by absolute CNA score is a statistically robust prognostic factor for survival in luminal A grade 3 breast cancer. Therefore, luminal A grade 3 breast cancer patients in CNA burden quartiles 3 or 4 may benefit from more aggressive therapy. This demonstrates how individual genomic landscapes can facilitate personalisation of therapeutic interventions to optimise survival outcomes.

scholarly journals Microvessel Density and Mammaglobin A Expression as Prognostic Markers in Molecular Types of Breast Cancer

2019 ◽  
Vol 70 (7) ◽  
pp. 2671-2676
Author(s):  
Adriana Andreea Jitariu ◽  
Amalia Raluca Ceausu ◽  
Adriana Meche ◽  
Cristian Nica ◽  
Amelia Burlea ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Microvessel Density ◽  
Ductal Carcinoma ◽  
Hot Spot ◽  
Histopathological Diagnosis ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Mean Values

Increased microvessel density (MVD) values in breast cancer correlate with tumor growth and progression while mammaglobin (MGB) expression in tumor cells is associated with a favorable prognosis. We aim to evaluate and correlate MVD values with MGB expression in molecular types of breast cancer specimens and to determine their utility as prognostic biological markers. A number of 52 breast cancer specimens were included in the study. Specimens were processed for routine histopathological diagnosis followed by the molecular classification by means of estrogen (ER), progesterone (PR) and HER2 immunohistochemical reactions. After performing immunohistochemistry for CD34 and MGB, MVD evaluation was made using the �hot spot� method for each case and MGB was scored between 0 (negative) and +3 (strong positive) depending on the intensity and distribution of the staining. MGB expression in tumor cells and MVD mean values were extremely variable. The greatest MVD mean values were obtained in luminal B followed by HER2, luminal A and triple negative breast cancer (TNBC) (95.33, 69, 62, and 40, respectively). MGB expression in the tumor cells generally ranged from mild to weak and was strong only in a few invasive ductal carcinoma cases. In cases with TNBCs the expression of MGB in tumor cells was weak and focal or negative. This variability was noticed between the molecular types of breast cancers and even within the same molecular type. In a restricted number of cases, MGB positive tumors were associated with low MVD values while the negative cases were characterized by increased MVD mean values. The variable results we obtained regarding the correlation between MVD and MGB in breast cancer specimens may indicate a rather restricted use of MVD/MGB in estimating breast cancer patients� prognosis.

scholarly journals Performing Data Mining to Explain the Correlation between the BIRC5 Gene and Prognosis in Breast Cancer Patients

2020 ◽  
Author(s):  
Hong Dongsheng ◽  
Zhang YanFang ◽  
Ye Ziqi ◽  
Chen Jing ◽  
Lu Xiaoyang
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Cancer Cell Line ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Luminal B ◽  
Kaplan Meier ◽  
Er Positive

Abstract Background: Breast cancer is the most commonly malignant cancers in women, and BIRC5 has been found to be overexpressed in a variety of human tumors. Its expression is associated with the prognosis of many cancers. However, whether BIRC5 mRNA could be used as an independent prognostic factor for breast cancer remains inconsistent in previous studies.Methods: Altered BIRC5 expression in normal tissue relative to various tumor tissue and in breast cancer patients with different molecular subtypes, clinical outcomes and chemotherapy responses were examined using the Oncomine, GOBO and Kaplan-Meier plotter datasets.Results: We found that many breast cancers had increased BIRC5 mRNA expression, and GOBO analysis showed that triple-negative cell lines displayed highest BIRC5 mRNA expression levels in the breast cancer cell line panel. Moreover, BIRC5 high mRNA expression was significantly associated with longer relapse-free survival (RFS) in all breast cancer patients. In particular, sub analysis revealed that high mRNA expression of BIRC5 was significantly associated with better survival in ER positive (HR = 2.05, p = 1e-16), but not in ER negative breast cancer (HR = 1.24, p = 0.1), furthermore, the results also demonstrated that BIRC5 high expression was significantly associated with longer RFS in luminal A (HR = 1.51, p = 3.1e-06) and luminal B (HR = 1.28, p = 0.026).Conclusions: In conclusion, BIRC5 is involved in the development and progression of breast cancer and may be a suitable prognostic marker for human breast cancer.

scholarly journals The St. Gallen 2019 Guidelines understages the Axilla in Lobular Breast Cancer a Population-Based Study

2021 ◽  
Author(s):  
Ulrik Narbe ◽  
Par-Ola Bendahl ◽  
Marten Ferno ◽  
Christian Ingvar ◽  
Looket Dihge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Adjuvant Chemotherapy ◽  
Axillary Lymph Node ◽  
Study Cohort ◽  
Axillary Lymph ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
National Quality

Background The St. Gallen 2019 guidelines recommend omission of completion axillary lymph node dissection (cALND) in breast cancer patients with 1-2 sentinel lymph node (SLN) metastases regardless of histopathology. Concurrently, adjuvant chemotherapy is endorsed for luminal A-like disease with ≥4 axillary lymph node (ALN) metastases. We aimed to estimate the proportion of patients with invasive lobular cancer (ILC) and invasive ductal cancer of no special type (NST) and 1-2 SLN metastases for whom cALND would indicate need of adjuvant chemotherapy. Methods Patients with ILC and NST histopathology undergoing primary surgery 2014-2017 were identified in the Swedish National Quality Breast Cancer register. After exclusion of patients with incongruent or missing data, 1886 patients who fulfilled the St. Gallen 2019 criteria for cALND omission were included in the study cohort. Results Patients with ILC (n = 329) had a higher metastatic nodal burden and more often a luminal A-like subtype compared with NST patients (n = 1507). The prevalence of ≥ 4 ALN metastases was higher in ILC (31%) than in NST (15%), corresponding to an adjusted odds of 2.26 (95% CI 1.59-3.21). Luminal A-like breast cancers with ≥4 ALN metastases were overrepresented in ILC cases (52/281 (19%)) compared to NST cases (43/1299 (3%)), P<0.001. Conclusions Patients with ILC more often had a luminal A-like breast cancer with ≥4 ALN metastases compared with NST patients. Abstaining cALND in patients with luminal A-like ILC with 1-2 SLN metastases warrants future attention as it risks nodal understaging and hence undertreatment in one-fifth of these patients.

scholarly journals Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer

2013 ◽  
Vol 20 (3) ◽  
pp. 339-348 ◽  
Author(s):  
Sewha Kim ◽  
Do Hee Kim ◽  
Woo-Hee Jung ◽  
Ja Seung Koo
Keyword(s):  
Breast Cancer ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Glutamine Metabolism ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Luminal B ◽  
Related Proteins ◽  
Glutaminase 1

The aim of this study was to investigate the expression of glutamine metabolism-related proteins to determine whether glutamine is metabolized differently according to breast cancer molecular subtype. We generated a tissue microarray of 702 breast cancer patients and performed immunohistochemical staining for glutamine metabolism-related proteins, including glutaminase 1 (GLS1 (GLS)), glutamate dehydrogenase (GDH (H6PD)), and amino acid transporter-2 (ASCT2 (SLC1A5)), which were separately evaluated in tumor and stroma compartments and then analyzed by breast cancer molecular subtypes. Breast cancers were classified as follows: 293 luminal A (41.7%), 166 luminal B (23.6%), 67 HER2 type (9.6%), and 176 TNBC (25.1%). HER2 type showed the highest stromal GLS1 (P=0.001), tumoral GDH (P=0.001), stromal GDH (P<0.001), and tumoral ASCT (P<0.001) expression. We identified differential expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer. The highest glutamine metabolic activity was seen in HER2-type breast cancer.

scholarly journals Can Color and Spectral Doppler Ultrasound of Breast Cancers Help to Predict the Immunohistochemistry profile?

2019 ◽  
pp. 161-167
Author(s):  
Afsaneh Alikhassi ◽  
Soodabeh Zamani Nokandeh ◽  
Kazem Mousavi ◽  
Hana Saffar ◽  
Masoumeh Gity ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Doppler Ultrasound ◽  
Color Doppler ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Color Flow ◽  
Er Positive ◽  
Spectral Doppler ◽  
Doppler Color

  Purpose: To determine the relationship between color and spectral Doppler features of breast cancers and their biomarkers. Patients and Methods: From January 2017 to January 2018, 43 patients with breast cancer were enrolled. Age, existence of color flow in the Doppler ultrasound, color flow pattern, tumor size, and immunohistochemistry (IHC) subtypes were recorded. Results: Among 43 breast cancer patients, IHC profiles showed that 36 patients were estrogen (ER) positive, 30 patients were progesterone (PR) positive, and 12 patients were human epidermal growth factor receptor 2 (Her2) positive. The prevalence of biomarker groups in this study were as follows: luminal A, 21 patients (48.83%); luminal B, 15 (34.88%); Her 2 amplifier, 2 (4.65%); and triple negative, 5 (11.62%). Thirty-seven patients (86.04%) with malignant masses had detectable flow and six patients (13.95%) had no detectable flow. The ER-positive and PR-positive breast cancers had the highest vascular presence rate in color Doppler ultrasound but it was not statistically significant. Maximum vessel diameter in different biomarker groups and Doppler color patterns with various biomarkers showed no significant differences. Conclusion: It is not possible to predict breast cancer biomarker groups using available color Doppler features and indexes, so pathology with IHC is still required.  

scholarly journals The m6A-related gene signature for predicting the prognosis of breast cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11561
Author(s):  
Shanliang Zhong ◽  
Zhenzhong Lin ◽  
Huanwen Chen ◽  
Ling Mao ◽  
Jifeng Feng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Cancer Survival ◽  
Risk Group ◽  
Gene Signature ◽  
Breast Cancer Survival ◽  
Breast Cancer Patients ◽  
Related Gene ◽  
Rna Methylation

N6-methyladenosine (m6A) modification has been shown to participate in tumorigenesis and metastasis of human cancers. The present study aimed to investigate the roles of m6A RNA methylation regulators in breast cancer. We used LASSO regression to identify m6A-related gene signature predicting breast cancer survival with the datasets downloaded from Gene Expression Omnibus and The Cancer Genome Atlas (TCGA). RNA-Seq data of 3409 breast cancer patients from GSE96058 and 1097 from TCGA were used in present study. A 10 m6A-related gene signature associated with prognosis was identified from 22 m6A RNA methylation regulators. The signature divided patients into low- and high-risk group. High-risk patients had a worse prognosis than the low-risk group. Further analyses indicated that IGF2BP1 may be a key m6A RNA methylation regulator in breast cancer. Survival analysis showed that IGF2BP1 is an independent prognostic factor of breast cancer, and higher expression level of IGF2BP1 is associated with shorter overall survival of breast cancer patients. In conclusion, we identified a 10 m6A-related gene signature associated with overall survival of breast cancer. IGF2BP1 may be a key m6A RNA methylation regulator in breast cancer.

scholarly journals Identification of a Novel Glycolysis-Related Gene Signature for Predicting Breast Cancer Survival

2021 ◽  
Vol 10 ◽  
Author(s):  
Dai Zhang ◽  
Yi Zheng ◽  
Si Yang ◽  
Yiche Li ◽  
Meng Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Survival ◽  
Cox Regression ◽  
Gene Signature ◽  
Breast Cancer Survival ◽  
Breast Cancer Patients ◽  
Related Gene ◽  
Training Set ◽  
Cox Regression Analysis ◽  
Kaplan Meier

To identify a glycolysis-related gene signature for the evaluation of prognosis in patients with breast cancer, we analyzed the data of a training set from TCGA database and four validation cohorts from the GEO and ICGC databases which included 1,632 patients with breast cancer. We conducted GSEA, univariate Cox regression, LASSO, and multiple Cox regression analysis. Finally, an 11-gene signature related to glycolysis for predicting survival in patients with breast cancer was developed. And Kaplan–Meier analysis and ROC analyses suggested that the signature showed a good prognostic ability for BC in the TCGA, ICGC, and GEO datasets. The analyses of univariate Cox regression and multivariate Cox regression revealed that it’s an important prognostic factor independent of multiple clinical features. Moreover, a prognostic nomogram, combining the gene signature and clinical characteristics of patients, was constructed. These findings provide insights into the identification of breast cancer patients with a poor prognosis.

scholarly journals Tamoxifen resistance mechanisms in breast cancer treatment

2020 ◽  
Vol 8 (2) ◽  
pp. 224-232
Author(s):  
Asima Tayyeb
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Molecular Mechanisms ◽  
Tamoxifen Resistance ◽  
Resistance Mechanisms ◽  
Breast Cancer Treatment ◽  
Therapeutic Interventions ◽  
Survival Outcomes ◽  
Breast Cancer Patients ◽  
Current Review

Therapies targeting estrogen receptor (ER) are being widely used to treat ER+ breast cancer patients. Despite early detection and improved survival outcomes, tamoxifen resistance, either intrinsic or acquired- is a major obstacle in effective disease management. Current review will summarize different molecular mechanisms of tamoxifen resistance both intrinsic and acquired in breast cancer treatment. This review not only provides basis to understand the nature of tamoxifen drug resistance but also suggests the mechanisms for its control leading to improved therapeutic interventions.

scholarly journals Quantitative Mammographic Density Measurements and Molecular Subtypes in Chinese Women with Breast Cancer

2020 ◽  
Author(s):  
Yuan Tian ◽  
Jennifer L Guida ◽  
Hela Koka ◽  
Er-Ni Li ◽  
Bin Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Mammographic Density ◽  
Chinese Women ◽  
Statistical Tests ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B

Abstract Background Studies investigating associations between mammographic density (MD) and breast cancer subtypes have generated mixed results. We previously showed that having extremely dense breasts was associated with the HER2-enriched subtype in Chinese breast cancer patients. Methods In this study, we re-evaluated the MD-subtype association in 1,549 Chinese breast cancer patients, using VolparaDensity software to obtain quantitative MD measures. All statistical tests were two-sided. Results Compared to women with luminal A tumors, women with luminal B/HER2- (odds ratio [OR]=1.20, 95% confidence interval [CI]: 1.04-1.38, p = 0.01), luminal B/HER2 + (OR = 1.22, 95% CI: 1.03-1.46, p = 0.03), and HER2-enriched tumors (OR = 1.30, 95% CI: 1.06-1.59, p = 0.01) had higher fibroglandular dense volume. These associations were stronger in patients with smaller tumors (&lt;2cm). In contrast, the triple negative subtype was associated with lower non-dense volume (OR = 0.82, 95% CI: 0.68-0.99, p = 0.04), and the association was only seen among older women (&gt;50 years old). Conclusion Although biological mechanisms remain to be investigated, the associations for the HER2-enriched and luminal B subtypes with increasing MD may partially explain the higher prevalence of luminal B and HER2+ breast cancers previously reported in Asian women.

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