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

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.

Breast Care ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. 248-252 ◽  
Author(s):  
Muhammet A. Kaplan ◽  
Ulku Y. Arslan ◽  
Abdurrahman Işıkdogan ◽  
Faysal Dane ◽  
Berna Oksuzoglu ◽  
...  

Purpose: The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in breast cancer patients who had undergone curative surgery. Methods: We retrospectively evaluated 1,350 breast cancer patients with relapses after curative surgery between 1998 and 2012 from referral centers in Turkey. Patients were divided into 4 biological subtypes according to immunohistochemistry and grade: triple negative, HER2 overexpressing, luminal A and luminal B. Results: The percentages of patients with luminal A, luminal B, HER2-overexpressing, and triple-negative breast cancer were 32.9% (n = 444), 34.9% (n = 471), 12.0% (n = 162), and 20.2% (n = 273), respectively. The distribution of metastases differed among the subgroups: bone (66.2% and 53.9% in luminal A and B vs. 38.9% in HER2-overexpressing and 45.1% in triple negative, p < 0.001), liver (40.1% in HER2-overexpressing vs. 24.5% in luminal A, 33.5% in luminal B, and 27.5% in triple negative, p < 0.001), lung (41.4% in triple negative and 35.2% in HER2-overexpressing vs. 30.2% and 30.6% in luminal A and B, p = 0.008) and brain (25.3% in HER2-overexpressing and 23.1% in triple negative vs. 10.1% and 15.1% in luminal A and B, p < 0.001). Conclusions: Organ-specific metastasis may depend on the molecular subtype of breast cancer. Tailored strategies against distant metastasis concerning the molecular subtypes in breast cancer should be considered.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Dongning Shi ◽  
Junwen Bai ◽  
Yibo Chen ◽  
Xia Wang ◽  
Yafeng Zhang ◽  
...  

Background. To determinate the association relationship of breast cancer bone metastasis and cancer characteristics and molecular subtype. Furthermore, to evaluate the impact of molecular subtype on prevalence and prognosis of bone metastasis from the breast cancer base on a large population real-word program, the Surveillance, Epidemiology, and End Results (SEER) database. Methods. We collected and analyzed the data obtained from SEER, which showed molecular subtype information for each patient. The prevalence and outcome of bone metastasis in breast cancer were estimated as per the different molecular subtypes. Results. Occurrence of bone metastasis in conformity with four different molecular subtypes in all 42684 breast cancer patients was 6.2, 9.4, 7.9, and 6.4%, respectively. The most unfavorable subtype was the triple-negative breast cancer (TNBC), followed by the luminal A, luminal B, and HER2 subtypes (hazard ratio [HR] of luminal A compared with TNBC, 0.533, 95% confidence interval, 0.444–0.641; HR of luminal B, 0.482, 95% CI 0.419–0.555; HR of HER2 subtype, 0.542, 95% CI 0.484–0.608). Brain metastasis impacts overall survival (OS) ( p < 0.001 ) fundamentally, and visceral metastases also significantly decreased OS ( p < 0.001 ). Conclusion. Bone metastasis patients present a more favorable oncological survival consequence than other metastases, and the TNBC subtype with bone metastasis showed the poorest tumor outcome compared with the other three molecular subtypes.


2020 ◽  
Vol 19 (1) ◽  
pp. 55-58
Author(s):  
Shafatujjahan ◽  
Ifatujjahan ◽  
Rajat Sanker Roy Biswas

Introduction: Breast cancer is a common malignancy among female in Bangladesh.But its molecular subtypes are not evaluated due to lack of expert investigationsupport. So objectives of the present study are to evaluate the molecular subtypesof breast cancer patients according to St Gallen classification in our contest. Materials and methods: It is retrospective study done among histopathologicallyproved 40 breast cancer patients visiting Medical Oncology and Radiotherapydepartment of Chattogram Maa-O-Shishu Hospital. Molecular subtypes wasevaluated by immunohistochemistry according to St Gallen Classification. Results: In this study a total of 40 cases of invasive female breast cancers wereincluded. Age of the patients ranged from 31-62 years, with a mean age of 41 ±13.5 years. ER expression was seen in 60% and PR in 55% of cases and Her-2/neupositivity in 16%. Majority (52.5%) of the tumors were located in the left breast. Thepercentage of ER but not PR positivity increased with age, though this differencewas not statistically significant. Majority of the cases were diagnosed at stage IIwith a percentage of 42.5%. Stage II tumors showed more ER and PR positivity.Among all 57.9% of ER positive and 49.5% of PR positive tumors were present while72.2% of tumors were negative for Her-2/neu. The triple-negative breast tumorswere more commonly found at grade 2. Regarding luminal status 14(35%) wasLuminal A, 5(12.5%) was Luminal B, 9(22.5%) was TNBC and 12(30%) was HER 2positive. Conclusion: In this study luminal A was the commonest molecular subtypes. LuminalA subtypes tumors had a long term risk of distant matastatic disease which can bereduced by hormonal treatment. Chatt Maa Shi Hosp Med Coll J; Vol.19 (1); January 2020; Page 55-58


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12575-e12575 ◽  
Author(s):  
Ramses F. Sadek ◽  
Li fang Zhang ◽  
Houssein Talal Abdul Sater

e12575 Background: Breast Cancer (BC) has been classified into four subtypes: Luminal A (LABC), Luminal B (LBBC), Triple negative (TNBC) and HER2-enriched (HER2e). BC mortality in Black women is significantly higher than in Whites and Asians. BC in Blacks has been characterized by higher grade and later stage. Causes of the Black-White BC survival disparity have been investigated, including differences in: diagnostic stage, socioeconomics, and comorbidities. These have led researchers to investigate the differences in tumor molecular subtype and their association with clinical outcomes and races. Methods: This study used the Surveillance, Epidemiology, and End Results – 18 (SEER-18) Registries research data between 2010 and 2013 that included over 212,000 patients. Descriptive statistics, Odds ratios (OR) and 95%Confidence intervals (CI) were used to study the association between BC stage, grade, and mortality and BC molecular subtypes across different races. We employed Cox regression models to explore the race disparity in BC mortality before and after controlling for BC molecular subtype and other clinical and social factors. Results: TNBC had more high grade cancer compared to HER2e subtype (OR, 1.5; CI, 1.3 - 1.8), LBBC (OR, 4.5; CI, 4.0 - 5.0) and LABC (OR, 12.2; CI, 11.2 – 13.3) for Black. BC mortality was higher in TNBC subtype compared to HER2e subtype (OR, 1.3; CI, 1.1 - 1.6), LBBC (OR, 2.4; CI, 2.0 - 2.9), and LABC (OR, 2.8; CI, 2.4 – 3.2) for Blacks. Results are consistent for all races. HER2e subtype had more late cancer stage compare to LBBC (OR, 1.2; CI, 1.0 - 1.4), TNBC (OR, 1.4; CI, 1.2 - 1.6) and LABC (OR, 2.1; CI, 1.8 - 2.4) in Blacks with similar results in all races. BC mortality in Blacks was higher compare with Whites (HR, 1.9; CI, 1.8 - 2.0) and Asian (HR, 2.7; CI, 2.5 - 3.0). After controlling for cancer subtype and other factors in the Cox regression model, the corresponding HRs ware significantly decreased to 1.2 (CI, 1.1 -1.3) and 1.6 (9CI, 1.5 -1.8). Blacks have heighst percent in stage IV and grade higer grade of disease. Conclusions: Molecular subtypes of BC contribute differently to risks of late cancer stage, high cancer grade and BC specific mortality. These differences are consistent in all races. The molecular subtypes and other social and clinical factors may explain part of the BC mortality race disparity.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e13075-e13075
Author(s):  
Lúcio Lara Santos ◽  
Fernando Miguel ◽  
Lygia Vieira Lopes ◽  
Julio Oliveira ◽  
Eduardo Ferreira ◽  
...  

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.


2020 ◽  
Author(s):  
Hong Dongsheng ◽  
Zhang YanFang ◽  
Ye Ziqi ◽  
Chen Jing ◽  
Lu Xiaoyang

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Kyoungmin Lee ◽  
Sung Hoon Sim ◽  
Eun Joo Kang ◽  
Jae Hong Seo ◽  
Heejung Chae ◽  
...  

Background: The role of chemotherapy for isolated locoregional recurrence (iLRR) of breast cancer has not been firmly established after local therapies.Methods: We performed a multicenter, retrospective analysis to evaluate the clinical implications of chemotherapy in breast cancer patients with HER2-negative iLRR.Results: Of a total of 277 patients, 146 (52.7%) received chemotherapy for iLRR. Median follow-up duration was 56.1 months. Eighty-six (31.0%) patients had luminal B-like and 100 (36.1%) had TNBC iLRR. There was a trend of longer disease free survival (DFS) in the chemotherapy group (4-year DFS: 70.4 vs. 59.5%, HR = 0.68, 95% CI 0.45–1.02, log-rank p = 0.059). When adjusted with clinically relevant factors, DFS was significantly prolonged with chemotherapy (adjusted HR = 0.61, 95% CI 0.40–0.94, p = 0.023). Subgroup analyses for DFS showed patients with disease free interval (DFI) &lt;5 years or prior chemotherapy had a benefit from chemotherapy (adjusted HR = 0.57, p = 0.018; adjusted HR = 0.51, p = 0.005, respectively). Regarding the molecular subtypes, a longer DFS with chemotherapy was observed both in luminal B-like (4-year DFS: 77.8 vs. 55.0%, HR = 0.51, 95% CI 0.27–0.99, log-rank p = 0.048) and in TNBC patients (4-year DFS: 61.9 vs. 42.8%, HR = 0.49, 95% CI 0.24–1.02, log-rank p = 0.056), but not in luminal A-like.Conclusions: The chemotherapy for iLRR of breast cancer should be individualized for each patient, considering DFI, prior chemotherapy, and molecular subtypes.


2021 ◽  
Author(s):  
Dorsay Sadeghian ◽  
Hana Saffar ◽  
Pouya Mahdavi Sharif ◽  
Vahid Soleimani ◽  
Behnaz Jahanbin

Abstract Background: Currently, breast cancers are divided into four major molecular subtypes. The distinction between the luminal A and luminal B subtypes is mainly based on the cellular proliferation indices and is assessed by the Ki-67 scoring. Due to the limitations in the assessment and expression of Ki-67, we hypothesized that minichromosome maintenance protein 6 (MCM6) can be taken as a surrogate marker to differentiate molecular subtypes and aid in more precise grading of tumors. Methods: We performed a retrospective, cross-sectional study on 124 samples of breast cancer and 40 samples of normal breast tissue. Relevant clinical information was retrieved from the relevant Cancer Institute database.Results: MCM6 could discriminate between different histologic grades. The luminal B subtype exhibited a higher MCM6 score in comparison to luminal A (P=0.01). There were significantly higher MCM6 scores in the hormone receptor (HR) negative, in comparison to luminal breast cancers (P<0.001). MCM6 score had a significant correlation with the mitotic count (P<0.001).Conclusion: MCM6 can reliably differentiate luminal A and luminal B subtypes and was correlated with the mitotic counts. More studies are needed to standardize its assessment methods, determine more robust cut-off values, and evaluate its associations with prognostic features of breast cancer.


2021 ◽  
Vol 22 (24) ◽  
pp. 13540
Author(s):  
Judith Buentzel ◽  
Henry Gerd Klemp ◽  
Ralph Kraetzner ◽  
Matthias Schulz ◽  
Gry Helene Dihazi ◽  
...  

Malignant cells differ from benign ones in their metabolome and it is largely unknown whether this difference is reflected in the metabolic profile of their microvesicles (MV), which are secreted into the blood of cancer patients. Here, they are present together with MV from the various blood and endothelial cells. Harvesting MV from 78 breast cancer patients (BC) and 30 controls, we characterized the whole blood MV metabolome using targeted and untargeted mass spectrometry. Especially (lyso)-phosphatidylcholines and sphingomyelins were detected in a relevant abundance. Eight metabolites showed a significant discriminatory power between BC and controls. High concentrations of lysoPCaC26:0 and PCaaC38:5 were associated with shorter overall survival. Comparing BC subtype-specific metabolome profiles, 24 metabolites were differentially expressed between luminal A and luminal B. Pathway analysis revealed alterations in the glycerophospholipid metabolism for the whole cancer cohort and in the ether lipid metabolism for the molecular subtype luminal B. Although this mixture of blood-derived MV contains only a minor number of tumor MV, a combination of metabolites was identified that distinguished between BC and controls as well as between molecular subtypes, and was predictive for overall survival. This suggests that these metabolites represent promising biomarkers and, moreover, that they may be functionally relevant for tumor progression.


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