scholarly journals Relationship of Histopathology Grading with Molecular Subtypes of Breast Cancer Patients in Haji Adam Malik General Hospital 2016-2018

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

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.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13065-e13065
Author(s):  
Qian Dong ◽  
Mi Zhang ◽  
Da Jiang

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.


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 ◽  
Vol 42 (1) ◽  
pp. 75
Author(s):  
Suzita Hirachan ◽  
Yogendra P Singh

Introduction Breast cancer is the second most common malignancy in Nepalese women. It represents a group of heterogenous disease with diverse biologic, clinical and molecular characteristics requiring personalized treatment. Based on Immunohistochemical markers, breast cancer is classified into distinct molecular subtypes. The aim of the study was to analyze the incidence of molecular subtypes of all breast cancer patients treated at University Hospital of Nepal in the period over 3 years. MethodsA retrospective observational study was carried out in Breast Unit of Tribhuvan University Teaching Hospital, Kathmandu. Electronic medical records of all breast cancer patients treated between January 2017 to December 2019 were retrieved from the hospital database. Patient’s characteristic, histological features and molecular subtypes were collected and analyzed. ResultsA total of 156 surgically treated breast carcinoma patients were studied. The median age of study population was 55 years (range 28–82years). Among these, 69 (44%) were of ≤45 years and 87 (56%) were over 45 years. The mean tumor size was 29 mm (range 50-140 mm). The most common histology was invasive ductal carcinoma (93.5%). Luminal type A was positive in 68 (43%) patients while luminal type B was present in 12 (7.6%) patients. Triple negative subtype was observed in 50 (32%) patients while HER2 rich subtype was seen in 25(16%). Incidence of Triple negative subtype was highest in patients less than 45 years (42%). Luminal A subtype was correlated with low tumor grade and less positive lymph nodes metastasis. ConclusionThe most common molecular subtype of breast cancer in Nepal is Luminal A having favorable features. The incidence of triple negative breast cancer is higher in Nepal, having an aggressive and clinically distinct subtype and is important for personalized treatment plan.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 565-565
Author(s):  
Naoki Niikura ◽  
Shinobu Masuda ◽  
Mizuho Terada ◽  
Mayako Terao ◽  
Nobue Kumaki ◽  
...  

565 Background: Immunohistochemical (IHC) Ki67 has described it as a prognostic and predictive marker for breast cancer. The St. Gallen Consensus Meeting determined that Ki67 labeling index is chiefly important for distinguishing between “Luminal A” and “Luminal B (HER2 negative)” subtypes and is a predictive marker for chemotherapeutic efficacy. However, the high and low cutoff points remain controversial. Our objective is to compare survival in patients with low, intermediate, and high Ki67 levels in each subgroup. Methods: We retrospectively identified all the patients in the Tokai University breast cancer database for whom IHC Ki67 data were available between January 1, 2000, and December 31, 2010. Ki67 was defined as low if <10% Ki67 was detected, as Intermediate if 10–20% Ki67 was detected, and as high if >20% Ki67 was detected. To assess Ki67 levels and survival outcomes, survival curves were calculated using the Kaplan–Meier method and compared using the log-rank test. Results: We identified 1331 primary breast cancer patients without metastasis, of whom 686 received neoadjuvant or adjuvant chemotherapy. Patients with high Ki67 had poorer relapse-free survival (RFS) than patients with intermediate (p = 0.009) and low Ki67 (p < 0.001). Patients with intermediate Ki67 had poorer RFS than patients with low Ki67 (p < 0.001). In ER-positive cases (n = 1059), patients with high and intermediate Ki67 had poorer RFS than patients with low Ki67 (p < 0.001 and p = 0.002, respectively). In HER2-positive and ER-negative cases (n = 103), patients with high Ki67 had poorer RFS than patients with low Ki67 (p = 0.002). In triple-negative cases (n = 164), patients with high Ki67 tended to have poorer RFS than patients with low Ki67 (p = 0.064). Conclusions: Our data demonstrated that low, intermediate, and high Ki67 levels may be used to differentiate prognosis in ER-positive cancer patients as well as HER2-positive and triple-negative cancer patients.


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


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.


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.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11559-e11559
Author(s):  
Muhammet Ali Kaplan ◽  
Ülkü Yalçintas Arslan ◽  
Abdurrahman Isikdogan ◽  
Berna Oksuzoglu ◽  
Mevlude Inanc ◽  
...  

e11559 Background: Relapse is one of the most important risk factors in overall survival, and distant recurrence is related to a complex biologic interaction of seed and soil factors. The aim of the study was to investigate the association between the molecular subtypes and patterns of relapse in patients with curative surgery performed breast cancer. Methods: We retrospectively evaluated clinical data from 1126 breast cancer patients with relapses after their curative surgery between 1998 and 2012 from referral centers of Turkey. Study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression.Patients were divided into four biological subtypes according to IHC: triple negative (ER negative, PR negative, and HER2 negative), HER2 overexpressing (ER negative, PR negative, and HER2 positive), luminal B (ER and/or PR positive, HER2 positive), and luminal A (ER and/or PR positive, HER2 negative). Results: The proportion of patients with luminal A, Luminal B, HER2-overexpressing, and triple negative breast cancer was 42.0% (n=473), 23.0% (n=259), 13.3% (n=150), and 21,7% (n=244), respectively. Median time to relapse was 26.6 months. 22.5% of the patients (n=253) had multiple relapse sites. The incidence of first distant recurrence site was significantly different among the subtypes. Liver (31.8% vs. 22.4%, p=0.008), bone (42.2% vs 37.0%, p<0.001), and lung metastases (30.9% vs. 22.2%, p=0.019) were increased in HER2 overexpressing, luminal A and triple negative group as first relapse site compared with other groups, respectively. Brain metastasis was increased in HER2 overexpressing and triple negative groups (17.7%), compared with Luminal A and B groups (8.0%, 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 may be considered.


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