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 ◽  
...  

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 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


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.


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.


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 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.


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 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.


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