scholarly journals Metabolomic Profiling of Blood-Derived Microvesicles in Breast Cancer Patients

2021 ◽  
Vol 22 (24) ◽  
pp. 13540
Author(s):  
Judith Buentzel ◽  
Henry Gerd Klemp ◽  
Ralph Kraetzner ◽  
Matthias Schulz ◽  
Gry Helene Dihazi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Molecular Subtype ◽  
Ether Lipid ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Luminal B ◽  
High Concentrations ◽  
A Minor

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.

scholarly journals Biological Subtypes and Distant Relapse Pattern in Breast Cancer Patients After Curative Surgery (Study of Anatolian Society of Medical Oncology)

Breast Care ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. 248-252 ◽  
Author(s):  
Muhammet A. Kaplan ◽  
Ulku Y. Arslan ◽  
Abdurrahman Işıkdogan ◽  
Faysal Dane ◽  
Berna Oksuzoglu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Curative Surgery ◽  
Luminal B ◽  
Distant Relapse

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.

scholarly journals Karakteristik Klinikopatologik Pasien Kanker Payudara dengan Metastasis Tulang di RSUP Sanglah pada Tahun 2014 - 2018

e-CliniC ◽  
2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Putu Krishna B. S. Putra ◽  
I Wayan J. Sumadi ◽  
Ni Putu Sriwidyani ◽  
IG Budhi Setiawan
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Bone Metastasis ◽  
Cancer Patients ◽  
Invasive Carcinoma ◽  
Molecular Subtype ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Luminal B ◽  
Histopathological Type

Abstract: Breast cancer is the most common cancer in woman. Metastasis often occurs especially to the bones. This study was aimed to determine the characteristics of breast cancer patients with bone metastasis. This was a descriptive study with a cross-sectional design. Samples were 46 breast cancer patients with bone metastasis recorded at Sanglah Hospital from 2014 until 2018. Data of pathological examination archives of Oncology Surgery Division Medical Faculty of Udayana University/Sanglah General Hospital were used to obtain the clinicopathological characteristics of metastatic breast cancer patients based on age, lateralization, histopathological type, and tumor molecular subtype. The results showed that most cases of metastatic breast cancer were aged 40-49 years as many 21 patients (45.7%), minimal difference in lateralization between right breast as many 22 patients (47.8%) and left breast 23 patients (50%). The most common histopathological type was invasive carcinoma of no special type as many 34 patients (73.9%). The most common tumor subtype was the luminal B subtype as many 21 patients (45.7%). In conclusion, most patients of breast cancer with bone metastasis were 40-49 years old, invasive carcinoma of no special type, molecular subtype of luminal B, and no significant difference between lateralization to the right and left breast.Keywords: breast cancer, bone, metastasis, clinicopathological caharacteristics Abstrak: Kanker payudara merupakan jenis kanker yang paling sering dijumpai pada wanita. Metastasis sering terjadi terutama pada tulang. Penelitian ini bertujuan untuk mengetahui karakteristik pasien kanker payudara dengan metastasis tulang di RSUP Sanglah Denpasar. Jenis penelitian ialah deskriptif dengan desain potong lintang. Sampel penelitian ialah 46 pasien kanker payudara dengan metastasis tulang yang tercatat di RSUP Sanglah tahun 2014-2018. Data diambil dari arsip hasil pemeriksaan patologi di Subdivisi Bedah Onkologi, Departemen/Kelompok Staf Medis (KSM) Bedah Fakultas Kedokteran Universitas Udayana (FK UNUD)/RSUP Sanglah untuk mendapatkan karakteristik klinikopatologi pasien kanker payudara metastasis tulang berdasarkan usia, lateralisasi, tipe histopatologik, dan subtipe molekuler tumor. Hasil penelitian menunjukkan kasus terbanyak terjadi pada rentang usia 40-49 tahun sebanyak 21 orang (45,7%), dengan lateralisasi tidak jauh berbeda antara payudara kanan sebanyak 22 orang (47,8) dan kiri sebanyak 23 orang (50%). Tipe histopatologik yang lebih sering ditemukan yaitu invasive carcinoma of no special type sebanyak 34 orang (73,9%). Subtipe molekuler yang paling banyak ditemukan ialah subtipe luminal B sebanyak 21 orang (45,7%). Simpulan penelitian ini pasien kanker payudara dengan metastasis tulang berada pada rentang usia 40-49 tahun, invasive carcinoma of no special type, subtipe molekuler luminal B. dan lateralisasi payudara kanan dan kiri tidak jauh berbeda.Kata kunci: kanker payudara, metastasis, tulang, karakteristik klinikopatologik

Relationship between tumor size and metastatic site in patients with stage IV breast cancer: A large SEER-based study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13065-e13065
Author(s):  
Qian Dong ◽  
Mi Zhang ◽  
Da Jiang
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Tumor Size ◽  
Stage Iv ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Chi Square ◽  
Metastatic Site ◽  
Luminal B ◽  
Stage Iv Breast Cancer

e13065 Background: To analyze the correlation between tumor size and metastatic site in first-diagnosed stage IV breast cancer patients. Methods: Stage IV breast cancer patients diagnosed from 2010 to 2015 were screened by the Surveillance, Epidemiology, and End Results (SEER) database. The characteristics of clinical variables were represented by a frequency table, and the Chi-square test was used for comparison. At the same time, the Chi-square test was used to analyze the relationship between tumor size and organ metastasis. Correlation between tumor size and the prognosis of patients was contributed by KM curve and Log-rank test. Results: Regardless of tumor size, the proportion of bone metastasis was higher and brain metastasis was lower in breast cancer patients. There were significant differences in the site of metastases based on different subtype. Luminal A and Luminal B breast cancer had the highest proportion of bone metastases; brain metastasis accounted for the highest proportion in triple-negative breast cancer (TNBC); while the incidence of liver metastasis was the highest in Her-2(+) breast cancer. At the same time, the results indicated that Luminal A breast cancer with a tumor size > 5 cm was more likely to develop multi-site metastasis and lung metastasis, while Luminal B breast cancer with a tumor size ≤ 5 cm was more likely to develop liver metastasis. The results also revealed that TNBC patients with a tumor size of 0 - 2cm were more likely to develop bone metastasis than those with a tumor size > 5 cm, and the incidence of lung metastasis in triple-negative patients showed an increasing trend with the increase of tumor size. Conclusions: Based on subtype, we found that there was a significant difference between tumor size and metastatic site in patients with stage IV breast cancer, and the difference was statistically significant. This study provided evidence-based basis for decision-making of stage IV breast cancer treatment.

Impact of the molecular pathology of breast cancer on mortality rates and overall survival in a Haitian cancer clinic.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13588-e13588
Author(s):  
Joseph Bernard ◽  
Rebecca Henderson ◽  
Lynn Gabrielle Alexis ◽  
Doukens Patrick Gilbert ◽  
Lenz Sacha Christyl Pierre ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Mortality Rate ◽  
Molecular Subtype ◽  
Metastatic Breast ◽  
Molecular Classification ◽  
Luminal A ◽  
Luminal B ◽  
The Impact ◽  
Cancer Clinic

e13588 Background: Breast cancer in the most common malignancy among women in Haiti and is mostly diagnosed at an advanced stage. While it is well known that molecular subtype is a prognostic factor, it needs to be investigated among Haitian patients with breast cancer. This study aimed to evaluate the impact of molecular classification of breast cancer on the survival of patients managed in Haiti’s largest cancer clinic. Methods: A retrospective study was conducted on the breast cancer patients of Innovating Health International (IHI) in Port-au-Prince, Haiti from January 2014 to December 2018. Chart review included all patients with breast cancer and tested for molecular classification. Data on variables such as date of admission, age, TNM staging, molecular classification, outcome and date of death were collected for the analysis. Mortality rate and median overall survival (OS) were estimated as of December 31st, 2019 and stratified according to molecular subtypes. Results: Among the 948 breast cancer cases diagnosed for the study period, 234 (24.7%) of them had a complete molecular classification. The mean age was 51.5 years [range: 23-94]. 55.1% of the patients were ER-positive, among them 33.7% ER+/PR+/HER2-, 15.4% ER+/PR-/HER2-, 2.1% ER+/PR-/HER2+ and 3.8% ER+/PR+/HER+ (triple positive). There were overall 25.6% of luminal A and 29.5% of luminal B cases. 44.9% were ER-negative, among them 14.1% ER-/PR-/HER2+ (HER2-enriched) and 29.1% ER-/PR-/HER2- (triple-negative). 92.2% of the patients had advanced breast cancer (stages IIB to IV). 29.5% had metastatic breast cancer, 22.8% for luminal A cases, 27.0% for luminal B, 36.7% for HER2-enriched and 32.8% for TNBC. Overall mortality rate was 42.3%, respectively 33.3% for luminal A cases, 37.7% for luminal B, 42.4% for HER2-enriched cases and 55.9% for TNBC. Median OS was not yet reached for luminal A, luminal B and HER2-enriched breast cancer, with a respective mean survival of 52.4 months, 51.3 months and 51.6 months. However, OS was 30.6 months for triple-positive breast cancer and 23.7 months for TNBC. Conclusions: Patients with luminal A breast cancer were less likely to have metastatic disease and thus had lower mortality rate and better overall survival. This was likely due to its less aggressive biology and the availability of hormone therapy. Poor availability and inaccessibility of HER2-targeted drugs were the main cause of the higher mortality rate among HER2-enriched patients. TNBC remains the most aggressive subtype.

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 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 Combined use of absolutely quantitated cyclin D1 and Ki67 protein levels to improve prognosis of Luminal-like breast cancer

2020 ◽  
Author(s):  
Junmei Hao ◽  
Wenfeng Zhang ◽  
Yan Lv ◽  
Jiarui Zou ◽  
Yunyun Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cyclin D1 ◽  
Cancer Patients ◽  
D1 Protein ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Dot Blot ◽  
Luminal A ◽  
Surrogate Assay

AbstractPurposeBoth Ki67 and cyclin D1 are routinely used protein biomarkers of cell proliferation for breast cancer patients. Ki67 is used to differentiate Luminal A-like from Luminal-B like subtype in surrogate assay. These two proliferative factors are investigated in this retrospective study to evaluate their prognostic role on the overall survival (OS) of Luminal-like breast cancer patients.MethodThe cyclin D1 protein level was measured absolutely and quantitatively using Quantitative Dot Blot (QDB) method in 143 Luminal-like FFPE breast cancer specimens. An optimized cutoff at 0.71 μmole/g was identified and used to separate these specimens into cyclin D1 high and low groups alone, or in combination with Ki67, for overall survival (OS) analyses of these patients.ResultsCyclin D1 was found to be an independent prognostic factor from Ki67 in univariate and multivariate analysis. When both biomarkers were used to separate these Luminal-like specimens, the group with low expression of both biomarkers (n=52) had significantly improved 10 year survival probability at 94%, while the one with high expression of both markers (n=34) were at 41% based on Kaplan-Meier survival analysis of OS (Log rank test p<0.0001).ConclusionWe demonstrated cyclin D1 as an independent prognostic protein biomarker from Ki67 for Luminal-like breast cancers. The combined usage of cyclin D1 and Ki67 significantly improved the prognosis over current prevailing surrogate assay. We propose to incorporate cyclin D1 in surrogate assay to improve prognosis for Luminal-like breast cancer patients in future clinical practice.

Analysis of disseminated tumor cells (DTCs) in primary breast cancer patients with various molecular subtypes.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13000-e13000
Author(s):  
Ivonne Nel ◽  
Laura Weydandt ◽  
Annekathrin Höhn ◽  
Bahriye Aktas
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Primary Breast Cancer ◽  
Molecular Subtypes ◽  
Immunocytochemical Staining ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Primary Tumors ◽  
Luminal B

e13000 Background: Despite successful treatment of the primary tumor, recurrence occurs in about 30% of breast cancer patients. One reason might be hematogenous spread during early disease stages. Disseminated breast cancer cells (DTCs) preferentially migrate into the bone marrow (BM) at early stages of the disease. Due to low proliferation, DTCs are persistent against systemic chemotherapy and might cause metastatic relapse at a later stage. Methods: BM aspirates were collected from the anterior iliac crest of patients with primary mamma carcinoma during surgery. After density gradient centrifugation cell suspensions were transferred onto glass slides and subjected to immunocytochemical staining against pan-cytokeratin. DTCs were visualized in pink using alkaline phosphatase and short counterstaining with hematoxylin which colored the nuclei light blue. DTCs were semi-automatically detected and enumerated using the Aperio Versa microscope based scanning system with a rare events algorithm that was trained to identify DTC candidates according to color, shape, intensity and size. As a positive control with each run, we used reference slides with a mix of bone marrow cells and a defined number of HCT116 cells. Results: Between February 2019 and December 2020 BM aspirates from 158 primary breast cancer patients were collected. Per patient about 4 million BM cells were analyzed. DTC detection revealed a positivity rate of 29% (46 patients). Molecular subtype analysis of DTC positive patients showed that 37% of the primary tumors (17 patients) were luminal A and 37% (17 patients) luminal B. In 9% of the cases (4 patients), tumors were HER2 enriched and 15% (8 patients) were triple negative. DTC count indicated that the majority of luminal B patients had 11-20 DTCs whereas luminal A patients tended to have lower DTC quantities varying between 1 and 10 DTCs. Conclusions: DTCs may serve as independent prognostic markers. Follow-Up data might reveal whether DTC quantification and molecular subtypes at primary diagnosis can be used to stratify patients at elevated risk for recurrence.

The effect of molecular subtype on survival in a racially diverse cohort of patients with high-risk breast cancer receiving trimodality therapy.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 156-156
Author(s):  
J. L. Wright ◽  
C. Takita ◽  
J. E. Panoff ◽  
I. M. Reis ◽  
W. Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Black Women ◽  
Cancer Patients ◽  
Racial Differences ◽  
Molecular Subtype ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Trimodality Therapy ◽  
Black Patients ◽  
Post Menopausal

156 Background: To understand the origins of racial disparities in breast cancer outcomes, the relative importance of race must be examined in the context of molecular subtype. We assessed racial differences in progression-free survival (PFS) and overall survival (OS) in relation to subtype in a cohort of uniformly treated stage II-III breast cancer patients. Methods: We reviewed records of 582 consecutive patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 and evaluated the effect of demographic, tumor, and treatment characteristics on PFS and OS. Results: Median follow-up 44.7 months. Patients: 24% black, 76% white, 55% pre/peri-menopausal. Disease: stage II 30%, stage III 70%. Treatment: all had mastectomy and PMRT; 98% had chemotherapy. All ER+ patients received endocrine therapy. Black and non-black patients were similar in age, menopause status, stage, and completion of trimodality therapy. Black patients were more likely to be ER- (56% vs 38%, p=0.0001), PR- (69% vs 54%, p=0.002), and triple negative (TN) (46% vs 24%, p<.0001). Among ER+, there were no differences in menopause or PR status by race. Black patients had worse PFS (60.6% vs 78.3%, p=.001) and OS (72.8% vs 87.7%, p<.0001). There was no racial difference in PFS (p=0.229 and 0.273 respectively) or OS (p=0.113 and 0.097 respectively) among ER- or TN. Among ER+, black patients had worse PFS (55% vs 81%, p<.001) and OS (73% vs 91%, p<.0001). The difference in PFS was seen in the ER+/PR+/HER2- (“luminal A”) subgroup (p=.002) but not ER+/PR-/HER2- (“luminal B”) (p=0.129), and in the post-menopausal ER+/HER2- subgroup (p=.004) but not pre/perimenopausal ER+/HER2- (p=.150). On multivariate analysis, racial differences in PFS (p=.055) and OS (p=.052) were maintained in the luminal A postmenopausal subgroup. Conclusions: In a cohort of breast cancer patients black women had worse survival. This disparity was driven by (1) a higher proportion of ER- and TN tumors in the black women and (2) worse outcome of similarly treated post-menopausal black women with luminal A breast cancer. The efficacy of various types of endocrine therapy must be examined in the setting of racial diversity.

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