Biological mechanisms that trigger breast cancer (BC) tumor progression are molecular subtype dependent

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10581-10581 ◽  
Author(s):  
C. Sotiriou ◽  
C. Desmedt ◽  
B. Haibe-Kains ◽  
A. Harris ◽  
D. Larsimont ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Clinical Outcome ◽  
Tumor Size ◽  
Tumor Invasion ◽  
Molecular Mechanisms ◽  
Molecular Subtypes ◽  
Proliferation Index ◽  
P Value ◽  
Prognostic Impact

10581 Background: We have recently developed several gene expression indices related to hallmarks of breast cancer involving various biological processes such as tumor invasion, impairment of immune response, sustained angiogenesis, evasion of apoptosis and self- sufficiency in growth signal, and investigated their impact on clinical outcome. Here, we aim to refine our biological understanding and the prognostic impact of these indices according to the previously described molecular subtypes based on the estrogen (ER) and ERBB2 receptors. Methods: Each of these indices were developed in a series of 581 BC samples and then computed on several publicly available microarray studies totaling over 2100 BC patients. Multivariate analyses were used to study the dependency patterns between these indices, the molecular subtypes and their impact on survival. Results: ER-/ERBB2- and ERBB2+ subgroups were significantly associated with high expression levels of the proliferation, tumor invasion, angiogenesis and immune response indices. Multivariate analysis showed that in the ER+/ERBB2- subgroup, only tumor size and the proliferation and tumor invasion indices were significantly associated with clinical outcome, with the proliferation index having the largest HR and most significant p-value (HR 3.25; CI 2.31–4.56; p=1.2 10-11). In contrast, in the ER-/ERBB2- subgroup, only tumor size (HR 2.08; CI 1.14–3.81; p=0.01) and immune response index (HR 0.66; CI 0.46–0.95; p=0.02) were associated with prognosis whereas in the ERBB2+ tumors only nodal status (HR 3.40; CI 0.96–12.10; p=0.05) and tumor invasion index (HR 3.03; CI 1.32–6.95; p=0.009) showed significant association with survival. Of interest, proliferation index lost its significance as almost all ER- /ERBB2- and ERBB2 + tumors showed high proliferation levels. Conclusions: Although proliferation seems to be the strongest parameter predicting clinical outcome in ER+/ERBB2- subtype, immune response and tumor invasion appear to be the main molecular mechanisms associated with prognosis in the ER-/ERBB2- and ERBB2+ subgroups respectively. Defining these clinico-genomic models in the specific molecular subgroups will be the key to success for personalized medicine. No significant financial relationships to disclose.

Clinicopathological and Imaging Features Predictive of Clinical Outcome in Metaplastic Breast Cancer

2020 ◽  
Vol 16 (6) ◽  
pp. 729-738
Author(s):  
Ga Young Yoon ◽  
Joo Hee Cha ◽  
Hak Hee Kim ◽  
Hee Jung Shin ◽  
Eun Young Chae ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Tumor Size ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Imaging Features ◽  
Peritumoral Edema ◽  
Imaging Findings ◽  
Metaplastic Breast Cancer

Background: Metaplastic breast cancer (MC) is a rare disease, thus it is difficult to study its clinical outcomes. Objective: To investigate whether any clinicopathological or imaging features were associated with clinical outcome in MC. Methods: We retrospectively evaluated the clinicopathological and imaging findings, and the clinical outcomes of seventy-two pathologically confirmed MCs. We then compared these parameters between triple-negative (TNMC) and non-TNMCs (NTNMC). Results: Oval or round shape, and not-circumscribed margin were the most common findings on mammography, ultrasound (US), and magnetic resonance imaging (MRI). It was mostly a mass without calcification on mammography, and revealed complex or hypoechoic echotexture, and posterior acoustic enhancement on US, and rim enhancement, wash-out kinetics, peritumoral edema, and intratumoral necrosis on MRI. Of all 72, 64 were TNMCs, and eight were NTNMCs. Clinicopathological and imaging findings were similar between the two groups, except that MRI showed peritumoral edema more frequently in TNMCs than NTNMCs (p=0.045). There were 21 recurrences and 13 deaths. Multivariable analysis showed that larger tumor size and co-existing DCIS were significantly predictive of Disease free survival (DFS), and larger tumor size and neoadjuvant chemotherapy were significantly predictive of overall survival (OS). Conclusion: MC showed characteristic imaging findings, and some variables associated with survival outcome may help to predict prognosis.

scholarly journals Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 147
Author(s):  
Leticia Díaz-Beltrán ◽  
Carmen González-Olmedo ◽  
Natalia Luque-Caro ◽  
Caridad Díaz ◽  
Ariadna Martín-Blázquez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Biomarker Discovery ◽  
Molecular Subtypes ◽  
Breast Cancer Subtype ◽  
P Value ◽  
Plasma Samples ◽  
Breast Cancer Patients ◽  
Clinical Value ◽  
Molecular Phenotypes

Purpose: The aim of this study is to identify differential metabolomic signatures in plasma samples of distinct subtypes of breast cancer patients that could be used in clinical practice as diagnostic biomarkers for these molecular phenotypes and to provide a more individualized and accurate therapeutic procedure. Methods: Untargeted LC-HRMS metabolomics approach in positive and negative electrospray ionization mode was used to analyze plasma samples from LA, LB, HER2+ and TN breast cancer patients and healthy controls in order to determine specific metabolomic profiles through univariate and multivariate statistical data analysis. Results: We tentatively identified altered metabolites displaying concentration variations among the four breast cancer molecular subtypes. We found a biomarker panel of 5 candidates in LA, 7 in LB, 5 in HER2 and 3 in TN that were able to discriminate each breast cancer subtype with a false discovery range corrected p-value < 0.05 and a fold-change cutoff value > 1.3. The model clinical value was evaluated with the AUROC, providing diagnostic capacities above 0.85. Conclusion: Our study identifies metabolic profiling differences in molecular phenotypes of breast cancer. This may represent a key step towards therapy improvement in personalized medicine and prioritization of tailored therapeutic intervention strategies.

scholarly journals Polypeptide-GalNAc-Transferase-13 Shows Prognostic Impact in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5616
Author(s):  
Eugenia Fernandez ◽  
Luis Ubillos ◽  
Nabila Elgul ◽  
María Florencia Festari ◽  
Daniel Mazal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Nodes ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Health Concern ◽  
Breast Cancer Cell Lines ◽  
Prognostic Impact ◽  
Metastatic Lymph Nodes ◽  
Metastatic Lymph

Breast cancer is a public health concern and is currently the fifth cause of mortality worldwide. Identification of different biological subtypes is essential for clinical management; therefore, the role of pathologists is essential and useful tools for immunohistochemistry diagnosis are needed. Polypeptide-GalNAc-transferases are emerging novel biomarkers related to cancer behavior and GalNAc-T13, correlated with aggressiveness in some tumors, is an interesting candidate. Few monoclonal antibodies reacting with native proteins, and not affected by fixation and paraffin embedding, have been reported. The aim of this work was to develop a useful monoclonal antibody anti-GalNAc-T13 and to assess its potential significance in breast cancer diagnosis. We evaluated 6 human breast cancer cell lines, 338 primary breast tumors and 48 metastatic lymph nodes and looked for clinical significance correlating GalNAc-T13 expression with patients’ clinical features and survival. We found high GalNAc-T13 expression in 43.8% of the cases and observed a significant higher expression in metastatic lymph nodes, correlating with worse overall survival. We hypothesized several possible molecular mechanisms and their implications. We conclude that GalNAc-T13 may be a novel biomarker in breast cancer, useful for routine pathological diagnosis. Elucidation of molecular mechanisms related to aggressiveness should contribute to understand the role of GalNAc-T13 in breast cancer biology.

Expression of BCRP/ABCG2 Protein in Invasive Breast Cancer and Response to Neoadjuvant Chemotherapy

2021 ◽  
Author(s):  
Yan Shou Zhang ◽  
Chao Yang ◽  
Lei Han ◽  
Lei Liu ◽  
Yun Jiang Liu
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Size ◽  
Hormone Receptor ◽  
Molecular Subtypes ◽  
Therapy Response ◽  
Luminal A ◽  
Luminal B ◽  
Response To Neoadjuvant Chemotherapy

Background: Breast cancer resistance protein (BCRP), or ABCG2 (ATP-binding cassette sub-family G member 2), is an ATP-binding cassette (ABC) transporter that mediates energy-dependent transport of substrate drugs out of the cell. Its overexpression may contribute to intrinsic drug resistance in vitro. However, the current literature has not yet clarified the clinical significance of BCRP/ABCG2 in invasive breast carcinoma. Objectives: The purpose of this study was to validate the expression of BCRP/ABCG2 in invasive breast carcinoma and its role in response to neoadjuvant chemotherapy. Methods: In this study, a pretherapeutic core biopsy was performed in 222 patients. BCRP/ABCG2 expression in carcinoma tissue was measured by immunohistochemistry. BCRP/ABCG2 expression correlations with clinicopathological features, molecular subtypes, and therapy response after neoadjuvant chemotherapy were investigated. Results: The results showed that BCRP/ABCG2 was expressed in different molecular subtypes. The proportions of patients with high BCRP/ABCG2 expression were similar in luminal A and luminal B tumors (Luminal B, 80%; Luminal A, 78%), compared with other molecular subtypes (Triple-negative, 63%; HER-2+, 58%. P=0.05). BCRP/ABCG2 expression and the number of lymphatic metastases (&#119875;=0.001) and tumor size (&#119875;=0.011) demonstrated a statistically significant correlation. Low BCRP/ABCG2 expression was associated with an increased pathological complete response (pCR) rate of 38%, higher than the 19% in tumors with high BCRP/ABCG2 expression (P=0.002). In multivariable analysis, BCRP/ABCG2 and hormone receptor (HR) expression were identified as independent risk factors of pCR (P=0.003, P=0.013. respectively). Conclusions: BCRP/ABCG2 is highly expressed in hormone receptor-positive breast cancer. High BCRP/ABCG2 expression is associated with lymphatic metastasis, tumor size, and poor pCR. BCRP/ABCG2 may be a novel potential biomarker that can predict clinical progression and therapy response after neoadjuvant chemotherapy.

The Association of Body Mass Index and Adverse Clinico-Pathological Characteristics of Non-Metastatic Breast Cancer Among Patients from Saudi Arabia

2020 ◽  
Vol 106 (1_suppl) ◽  
pp. 8-8
Author(s):  
Bashayer Alghamdi ◽  
Reema Alghamdi ◽  
Raghad Khallaf ◽  
Konooz faisal ◽  
Raghad Bishnaq ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Saudi Arabia ◽  
Lymph Node ◽  
Body Mass ◽  
Tumor Size ◽  
P Value ◽  
Axillary Lymph ◽  
Receptor Status ◽  
The Mean

Background: Obesity is a global health problem, especially in the Arab region, the prevalence of obesity is increasing. High body mass index (BMI) is a risk factor for many diseases, including cancer. Noticeably, breast cancer (BC) cases in Saudi Arabia occur at a younger age than western countries and different life style behaviours such as maintaining healthy body weight and physical activity may play a role in this. In this study, we aimed to investigate the association between BMI and BC clinicopathological features. Methods: This retrospective study was conducted by reviewing the records of females diagnosed with non-metastatic BC over four years. The association between BMI and patients’ demographics, BC histological type, receptor status, differentiation grade, tumor size, involvement of axillary lymph node, and performed procedures was analysed. Result: We studied 315 patients with non-metastatic BC. The mean age at the time of diagnosis was 52.43 years ±11.63. The mean BMI was 30.21±5.77. The mean tumor size was 3.19 cm ± 3.52. We found that the mean age of diagnosis is significantly greater in obese women than other BMI groups with a P-value = 0.025. A significant relationship was observed between BMI classification and tumor size in obese female patients aged ⩾ 40 years with P-value=0.022 Conclusion: The relationship between BMI and BC is still not clear, in this study we found an association with age at diagnosis and tumor size in older patients, characteristics as histological types, receptor status, lymph node involvement, and grade were not statistically significant.

scholarly journals Calretinin expression in molecular subtypes of invasive carcinoma breast

2020 ◽  
Vol 8 (4) ◽  
pp. 1498
Author(s):  
Suryagayathri Venugopal ◽  
Cicy P. J. ◽  
Deepa S. ◽  
Sankar Sundaram
Keyword(s):  
Breast Carcinoma ◽  
Molecular Mechanisms ◽  
Invasive Carcinoma ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Prognostic Significance ◽  
P Value ◽  
Carcinoma Breast ◽  
Low Level ◽  
High Level

Background: Breast cancer is a leading cause of cancer death  in women worldwide. Breast carcinoma is currently managed by assessing clinicopathological features. Elucidation of molecular mechanisms of pathogenesis of breast carcinoma  may lead to the development of new targeted therapies, particularly in triple negative cancers. Literature shows a few studies on the expression of calretinin  in breast carcinoma particularly in basal like type and its prognostic significance.  In this study, authors are trying  to assess the expression of  a new marker calretinin in different molecular subtypes of invasive carcinoma breast.Methods: This study was done in  107 cases of invasive carcinoma breast specimens received in  Department of Pathology, Government Medical college, Kottayam from December  2017 to May 2019.Results: Among the molecular subtypes, Basal like tumours showed 68.4% of cases with high level and 31.6% of cases with low level calretinin expression which is comparable with the study by Farrag et al. All the other molecular subgroups showed predominantly low level of calretinin expression.Conclusions: Different molecular subtypes of invasive carcinoma breast showed varied calretinin expression. High level calretinin expression was significantly associated with grade 3 (p value = 0.002), ER negativity (p = 0.004), PR negativity (p = 0.018)  and Basal like molecular subtype (p : <0.001). This suggests that calretinin might play a role in pathogenesis of basal like breast carcinomas.

scholarly journals Comprehensive analysis based on DNA methylation and RNA-seq reveals hypermethylation of the up-regulated WT1 gene with potential mechanisms in PAM50 subtypes of breast cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11377
Author(s):  
Chongyang Ren ◽  
Xiaojiang Tang ◽  
Haitao Lan
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Molecular Subtypes ◽  
Wilms Tumor ◽  
Expression Profiles ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Body Region ◽  
Rna Seq

Background Breast cancer (BC), one of the most widespread cancers worldwide, caused the deaths of more than 600,000 women in 2018, accounting for about 15% of all cancer-associated deaths in women that year. In this study, we aimed to discover potential prognostic biomarkers and explore their molecular mechanisms in different BC subtypes using DNA methylation and RNA-seq. Methods We downloaded the DNA methylation datasets and the RNA expression profiles of primary tissues of the four BC molecular subtypes (luminal A, luminal B, basal-like, and HER2-enriched), as well as the survival information from The Cancer Genome Atlas (TCGA). The highly expressed and hypermethylated genes across all the four subtypes were screened. We examined the methylation sites and the downstream co-expressed genes of the selected genes and validated their prognostic value using a different dataset (GSE20685). For selected transcription factors, the downstream genes were predicted based on the Gene Transcription Regulation Database (GTRD). The tumor microenvironment was also evaluated based on the TCGA dataset. Results We found that Wilms tumor gene 1 (WT1), a transcription factor, was highly expressed and hypermethylated in all the four BC subtypes. All the WT1 methylation sites exhibited hypermethylation. The methylation levels of the TSS200 and 1stExon regions were negatively correlated with WT1 expression in two BC subtypes, while that of the gene body region was positively associated with WT1 expression in three BC subtypes. Patients with low WT1 expression had better overall survival (OS). Five genes including COL11A1, GFAP, FGF5, CD300LG, and IGFL2 were predicted as the downstream genes of WT1. Those five genes were dysregulated in the four BC subtypes. Patients with a favorable 6-gene signature (low expression of WT1 and its five predicted downstream genes) exhibited better OS than that with an unfavorable 6-gene signature. We also found a correlation between WT1 and tamoxifen using STITCH. Higher infiltration rates of CD8 T cells, plasma cells, and monocytes were found in the lower quartile WT1 group and the favorable 6-gene signature group. In conclusion, we demonstrated that WT1 is hypermethylated and up-regulated in the four BC molecular subtypes and a 6-gene signature may predict BC prognosis.

scholarly journals Molecular profiling of breast carcinoma with IHC surrogates in a tertiary care centre in South India

Biomedicine ◽  
2021 ◽  
Vol 41 (1) ◽  
pp. 75-81
Author(s):  
N. Priyathersini ◽  
J. Thanka ◽  
B Jayashree
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Tertiary Care ◽  
P Value ◽  
Her2 Receptor ◽  
Luminal A

Introduction and Aim: Breast cancer is the most common malignancy in females worldwide. Almost 1.4 million new cases have been diagnosed with breast cancer every year. This aims to study the clinicopathological profile and molecular subtypes of invasive breast carcinoma in resected mastectomy specimens over a period of 5 years. Materials and Methods:A retrospective study of 90 mastectomy and wide local resection specimens received during the period of January 2012 to June 2017 were analyzed. The clinical data of patients including age, gender, and stage of the diseasewere obtained from the medical records section. Immunohistochemical staining for Estrogen Receptor [ER], Progesterone Receptor[PR] and Human Epidermal Growth Factor Receptor 2HER2neu were done.The cases were classified according to the molecular classification based on the ER, PR and HER2 receptor status. Results: The peak incidence of breast carcinoma was in the age group 50 to 60 years. Invasive ductal carcinoma,Not otherwise specified[NOS] accounted for the most common histologic type. There was higher incidence of pT2 tumors in our study. The most common molecular subtype was luminal A, followed by triple negative tumors. These molecular subtypes associated well with Tumor grade and HGDCIS with a statistically significant p value of 0.001 and 0.015 respectively. An increased proportion of Grade 3 tumors were Triple Negative tumors. Conclusion:In breast carcinomas the routine histopathological features provide inexpensive method for understanding tumour biology and prognosis. It`s essential in areas with poor resources. ER, PR and HER2 assessment helps in identifying hormonal status and enables for hormone therapy and anti HER2 therapy.  

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