scholarly journals Molecular Subtypes of Breast Cancer Patients According to St Gallen Classification

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

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.


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.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13000-e13000
Author(s):  
Ivonne Nel ◽  
Laura Weydandt ◽  
Annekathrin Höhn ◽  
Bahriye Aktas

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.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22165-e22165
Author(s):  
Joseph A. Pinto ◽  
Claudio J. Flores ◽  
Priscila I. Valdiviezo ◽  
Rodolfo Velazco ◽  
MIguel Garay ◽  
...  

e22165 Background: To evaluate toll-like receptors (TLRs1-9) and IRAK 1,3 and 4 expression in a breast cancer patients dataset that were treated with NAC as prognostic factors in terms of recurrence-free survival (RFS). Methods: Weretrieved normalized gene expression data from a public database (GEO: GSE25066) that includes 253 samples of breast cancer patients treated with NAC (antracyclines/taxanes) profiled with the U133A microarray. The median of RFS was 3.2 years (52 relapses observed). Distribution of molecular subtypes was: Luminal A (31.2%), Luminal B (17.4%), HER2 (7.1%), Basal (36.4%) and Normal (7.9%). We build a ratio of target gene/reference gen (ATCB) with to obtain replicable cut-points in other datasets. Levels of Gene expression were divided in three cut-points (Q1, Q2, and Q3). A cox-model was used to select gene expression cut-points with significant effects in the RFS. Results: According to molecular subtypes, there were significant differences in expression of TLR5 (higher in basal and Luminal A), TLR6 and IRAK1 (higher in basal and HER2). There were not differences of expression according to the pathologic response. The multivariate analysis shown that genes associated with the RFS were: TLR5 (HR=2.1 for the lower quartile), TLR6 (HR=2.4 for upper Q2), IRAK1 (HR=2.0 for upper quartile) and IRAK 3 (HR=2.2 for upper Q2). A TLR-Score was constructed (1 point added for each unfavorable gene-group). Cases were grouped in two categories (score 0-1 as good prognostic and score ≥ 2 as poor prognostic). There were and overall significant differences in both score-groups (poor prognostic: HR=4.9). In Basal and luminal B tumors there were significant differences (logrank test: P<0.001 and P=0.014, respectively), in HER2 tumors there were differences although not significant (P=0.143). There were not differences in Luminal A tumors. Conclusions: These data support the exploration of a TLR expression-based score to predict for RFS in breast cancer treated with NAC.


2020 ◽  
Author(s):  
Yuan Tian ◽  
Jennifer L Guida ◽  
Hela Koka ◽  
Er-Ni Li ◽  
Bin Zhu ◽  
...  

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.


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.


2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 24-24
Author(s):  
Joaquina Martínez-Galán ◽  
Cynthia S. González Rivas ◽  
Julia Ruiz Vozmediano ◽  
Lucia Portellano ◽  
Juan Ramón Delgado

24 Background: Estrogen receptor (ER)-positive breast cancers are considered prognostically more favorable than ER-negative tumors and are often responsive to anti-estrogen therapy. Whereas tumors overexpressing HER2 are endocrine resistant and they require the blockage of the HER2 pathway in addition to estrogen deprivation. To evaluate epigenetics differences in tumor-related genes to ESR1 and HER2/neu status in primary breast cancer is the objective of this study. Methods: We quantified methylation levels of promoter of ERS1 which are to confer growth adventage to cells in 107 women with breast cancer. Real Time QMS-PCR SYBR green (methylation-specific PCR) was used to analyze the hypermethylation. Tumours were classified as phenotype basal, luminal A, Luminal B, and phenotype HER2+. Results: Presence of methylated ESR1 in serum of breast cancer patients was associated with ER-negative phenotype (p=0.0179). Of the available cases, 60 pts (56%) were Luminal A, 10 pts (9.3%) Luminal B, 13 pts (12%) Basal like, and 9 pts (8.4%) HER2+. We observed that methylated ERS1 was preferably associated with phenotype Basal Like and worse interval progression free and survival global though p > 0.05 and the amplification HER2+ was correlation with significant more frequent methylation gene (p<0.05). Thet hypermethylation of normal ERS1 and 14-3-3σ combined differentiated between breast cancer patients and healthy controls (p = 0.0001) with a sensitivity of 81% (95% CI: 72–88%) and specificity of 88% (95% CI: 78–94%). Conclusions: This study identifies the presence of variations in global levels of methylation promoters genes in healthy controls and breast cancer with different phenotype classes and shows that these differences have clinical significance. These showed that frequent methylation had a strong association with molecular phenotype of breast cancer and perhaps in the future can explain therapy resistance related to RE and HER2/neu status and this may be of significance in the assessment of targeted therapy resistance related to ER and HER2/neu status in breast cancer patients.


2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 219s-219s
Author(s):  
M. Caleffi ◽  
S. Simon ◽  
J. Bines ◽  
G. Werutsky ◽  
J. Soares Nunes ◽  
...  

Background: Breast cancer is the most common cancer in women in Brazil and worldwide. There is large variation in survival among patients and molecular subtypes are important prognostic factors. However, most of the data comes from developed countries such as the United States and in Europe. Aim: Our goal was to describe breast cancer patients' demographic and pathologic characteristics, as well as their survival according to estimated molecular subtypes, assessed by common immunohistochemistry stains. Methods: AMAZONA study is a retrospective cohort conducted from June 2008 to January 2009 including women of at least 18 years old, with histologically proven breast cancer diagnosed in the period between 1 January 2001 and 31 December 2001 and between 1 January 2006 and 31 December. Estimated molecular subtypes by local immunohistochemical stains were luminal A, luminal B, HER-2 positive and triple-negative. Data were obtained from medical records and public databases. Kaplan-Meier method was used for data description and log-rank test for comparison between the subgroups. Results: 2296 patients were included in this analysis. Mean age was 54 years. Most subjects included came from hospitals located in the southeast region of the country, treated in the public health system and had stage II invasive ductal carcinoma of breast. Regarding subtype, 71.3% had hormonal receptor positive disease, 15.7% were HER-2 positive and 21.1% had triple-negative breast cancer. Overall survival (OS) was significantly different among molecular subtypes and was independent of pathologic stage for stages II and III patients. For stage III patients 5-years OS for luminal A subtype was 75.8% and for triple-negative was 56.1% ( P .0002). Conclusion: Classification of breast cancer patients in predicted molecular subtypes using immunohistochemistry is currently available in most underdeveloped countries and is a useful prognostic tool that goes beyond clinical or pathologic stage.


2020 ◽  
Vol 2 (1) ◽  
pp. 28-37
Author(s):  
Muhammad Furqan ◽  
Pimpin Utama Pohan

Background: Breast cancer symptoms are often not felt clearly by patients, as a result many patients who come in an advanced stage. This will affect the prognosis and cure rate of the patient. There are several factors that influence the prognosis of breast cancer, including histopathological grade, and classic immunohistochemical markers such as estrogen receptors, progesterone receptors, and HER2. In addition, breast cancer can be 4 main molecular subtypes, namely Luminal A, Luminal B, HER2-Overexpression, and Triple Negative / Basal-Like. Objectives: This study aims to determine the relationship between histopathological grade with the molecular subtypes of breast cancer patients in Haji Adam Malik General Hospital in 2016-2018. Methods: This is analytical cross-sectional research using a consecutive-sampling technique. Data were obtained secondary from the medical records of breast cancer patients at Haji Adam Malik General Hospital in 2016-2018 and then analyzed with the chi-square test. From 1005 cases of breast cancer during the 2016-2018 period, 131 samples were taken in this study. Results: Of the 131 samples, the highest histopathological grade was grade 2 with 53 people  (40.5%), followed by 41 people (31.3%) with grade 3, and 37 people (28.2%) with grade 1. The most molecular subtypes were Luminal A with 38 people (29%), followed by 33 people (25.2%) with Luminal B, 31 people (23.7%) with HER-2 Overexpression, and 29 people (22.1%) with Triple Negative / Basal-like. From the analysis of the chi-square test obtained p value of 0.045. Conclusion: There is a relationship between histopathological grade with molecular subtypes of breast cancer patients. Keywords: breast cancer, histopathological grade, immunohistochemistry, molecular subtypes     Latar Belakang: Gejala-gejala kanker payudara sering tidak dirasakan dengan jelas oleh pasien, akibatnya banyak pasien yang datang dalam keadaan stadium lanjut. Hal ini akan mempengaruhi prognosis dan tingkat kesembuhan pasien. Terdapat beberapa faktor yang mempengaruhi prognosis dari kanker payudara, antara lain grading histopatologi, dan marker imunohistokimia klasik seperti reseptor estrogen, reseptor progesteron, dan HER2. Selain itu, kanker payudara dapat diklasifikasikan menjadi 4 subtipe molekuler utama, yaitu Luminal A, Luminal B, HER2-Overexpression, dan Triple Negative/Basal-Like. Tujuan: Penelitian ini bertujuan untuk mengetahui hubungan antara grading histopatologi dengan subtipe molekuler pasien kanker payudara di RSUP Haji Adam Malik Tahun 2016-2018. Metode: Penelitian ini merupakan penelitian analitik menggunakan desain cross-sectional dengan teknik pengambilan sampel consecutive-sampling. Data diperoleh secara sekunder dari rekam medis pasien kanker payudara di RSUP Haji Adam Malik pada tahun 2016-2018 dan kemudian dianalisis dengan uji chi-square. Dari 1005 kasus kanker payudara selama periode 2016-2018, diambil sampel pada penelitian ini sebanyak 131 buah rekam medis. Hasil: Dari 131 sampel, grading histopatologi terbanyak terdapat pada grade 2 dengan 53 orang (40,5%) , diikuti 41 orang (31,3%) dengan grade 3, dan 37 orang (28,2%) dengan grade 1. Subtipe molekuler terbanyak yaitu Luminal A dengan 38 orang (29%), diikuti 33 orang (25,2%) dengan Luminal B, 31 orang (23,7%) dengan HER-2 Overexpression, dan 29 orang (22,1%) dengan Triple Negative/Basal-like. Dari hasil uji chi-square diperoleh nilai p sebesar 0,045. Kesimpulan: Terdapat hubungan antara grading histopatologi dengan subtipe molekuler pasien kanker payudara. Kata kunci: grading histopatologi, imunohistokimia, kanker payudara, subtipe molekuler


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 583-583
Author(s):  
George Stathopoulos ◽  
Nikolaos Malamos ◽  
Christos Markopoulos ◽  
Athanasios Polychronis ◽  
Sotirios Rigatos ◽  
...  

583 Background: The Ki-67 antigen was identified the involvement in early steps of polymerase I-dependent ribosomal RNA synthesis. Although it seems that the protein has an important function in cell division, its exact role is still obscure and there is little published work on its overall function. The aim of the present study is to evaluate the contribution of Ki-67 level in respect of tumor recurrence in molecular classified groups of breast cancer patients. Methods: Breast cancer tumor samples were examined for histological confirmation and for estrogen and progesterone receptors, c-erb-B2 expression, proliferation with Grade and Ki-67. Ki-67 was divided in percentage levels, up to 20 and higher than 20%. Immunohistochemistry and Fluorescence in situ hybridization is described for the results of ER, PR, c-erb-B2, Ki-67 biomarkers. Formaldehyde – fixed breast samples were paraffin wax embedded and processed for paraffin sections. The primary antibodies used were: The monoclinal antibody ID5 (M7047, Dakocytomation, Carpinteria, CA) for the detection of ER, the monoclonal anti-PR antibody 636 was used. For the detection of Ki-67 we used monoclonal mouse anti-human Ki-67 MIB-1. The patients molecular classification was Luminal A, Luminal B, Her-2 subtype and basal cell (triple negative). Results: 847 breast cancer patients were recruited. 291 were group as Luminal A, 228 as Luminal B, 221 Her-2 subtype and 107 triple negative. Follow-up was from 3 years to 15 years since diagnosis. It was found that in Luminal A patients, none had Ki-67 higher than 20% and the recurrence was in 10.65%. In Luminal B, the Ki-67 was higher than 20% in 61% of the patients and recurrence 23.68%. In Her-2 subtype >20% Ki-67 was 78.94%, recurrence 17.19%. In triple negative > 20% Ki-67 was in 68.75% and recurrence in 29.90% of the patients. Conclusions: The data presented here indicate that Ki-67 level may be considered as one of valuable biomarkers in breast cancer patients process and recurrence.


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