scholarly journals Subtypes of Breast Cancer in Northern India- An Immunohistomolecular Subtypes of Invasive Breast Cancer

Author(s):  
Amit Kumar Sinha ◽  
Amrita Ghosh

Introduction: Breast cancer is a heterogeneous disease that may differ in therapeutic response and prognosis despite similarities in histopathologic types, grade and stage. Molecular studies have identified distinct subtypes of breast carcinoma each having unique recognisable phenotypes and clinical outcomes. Aim: To study the histomorphological features and Immunohistochemical (IHC) profile of breast cancer, to study the distribution of molecular subclass, and to study the morphological features of different molecular subclasses and to determine the association between the pathological features associated with adverse prognosis with the molecular subclass. Materials and Methods: Present study was a prospective cross-sectional observational study based on mastectomy specimens of 122 cases of consecutive cases of invasive breast cancer submitted from June 2012 to February 2014 in Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India. On IHC staining with Estrogen Receptors (ER), Progesterone Receptors (PR), Human Epidermal growth factor Receptor 2 (HER2), Cytokeratin (CK5/6) and Epidermal Growth Factor Receptor (EGFR) these cases were classified into Luminal A, Luminal B, HER2 overexpression, basal like and normal breast like molecular subclass. All statistical analysis were performed using Statistical Package for the Social Sciences (SPSS) version 16 (SPSS, Inc., Chicago, IL, USA). Results: The proportion of each subytpes detected in present study were: Luminal A-28.69% (35), Luminal B-17.21% (21), HER2 over expressing-25.41% (31), Basal Like Breast Carcinoma (BLBC)-26.23% (32) and the rest unclassified category (normal breast like)-2.46% (3). The following variables were significantly associated with molecular breast cancer subtypes. The tumours of BLBC and HER2 overexpressing were larger, poorly differentiated, higher mitotic index, more number of positive lymph nodes and with more geographic and central necrosis than Luminal A group. These features were statistically significant (p<0.05). Conclusion: Identification of molecular subtype of breast cancer is extremely important for predicting prognosis and therapeutic response of the breast cancers and thus has role in management of patients of breast cancers. BLBC is a molecular subtype of breast cancer known for its aggressive behaviour and poor prognosis is identified by expression of basal CKs.

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 837
Author(s):  
So-Woon Kim ◽  
Jinah Chu ◽  
Sung-Im Do ◽  
Kiyong Na

Background and Objectives: Kidney and brain protein (KIBRA) is a protein encoded by the WW and C2 domain containing 1 (WWC1) gene and is involved in the Hippo signaling pathway. Recent studies have revealed the prognostic value of KIBRA expression; however, its role in breast cancer remains unclear. The aim of this study was to examine KIBRA expression in relation to the clinical and pathological characteristics of patients with breast cancer and to disease outcomes. Materials and Methods: We analyzed the expression of KIBRA and its correlation with event-free survival (EFS) outcomes in resected samples from 486 patients with breast cancer. Results: KIBRA expression was significantly different among the molecular subgroups (low KIBRA expression: luminal A, 46.7% versus 50.0%, p = 0.641; luminal B, 32.7% versus 71.7%, p < 0.001; human epidermal growth factor receptor 2 (HER2)-enriched, 64.9% versus 45.5%. p = 0.001; triple-negative, 73.6% versus 43.8%, p < 0.001). Low KIBRA expression was also associated with high nuclear grade (60.4% versus 37.8%, p < 0.001), high histologic grade (58.7% versus 37.0%, p < 0.001), and estrogen receptor (ER) negativity (54.2% versus 23.6%, p < 0.001). Low KIBRA expression was significantly associated with poor EFS (p = 0.041; hazard ratio (HR) 1.658; 95% confidence interval (CI), 1.015–2.709). Low KIBRA expression was an independent indicator of poor prognosis (p = 0.001; HR = 3.952; 95% CI = 1.542–10.133) in triple-negative breast cancer (TNBC). Conclusion: Low KIBRA expression was associated with higher histological grade, ER negativity and poor EFS of breast cancer. In particular, our data highlight KIBRA expression status as a potential prognostic marker for TNBC.


2015 ◽  
Vol 33 (18) ◽  
pp. 2035-2040 ◽  
Author(s):  
Fei-Fei Liu ◽  
Wei Shi ◽  
Susan J. Done ◽  
Naomi Miller ◽  
Melania Pintilie ◽  
...  

Purpose To determine the prognostic and predictive value of intrinsic subtyping by using immunohistochemical (IHC) biomarkers for ipsilateral breast relapse (IBR) in participants in an early breast cancer randomized trial of tamoxifen with or without breast radiotherapy (RT). Patients and Methods IHC analysis of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6, epidermal growth factor receptor, and Ki-67 was conducted on 501 of 769 available blocks. Patients were classified as luminal A (n = 265), luminal B (n = 165), or high-risk subtype (luminal HER2, n = 22; HER2 enriched, n = 13; basal like, n = 30; or triple-negative nonbasal, n = 6). Median follow-up was 10 years. Results Classification by subtype was prognostic for IBR (10-year estimates: luminal A, 5.2%; luminal B, 10.5%; high-risk subtypes, 21.3%; P < .001). Luminal subtypes seemed to derive less benefit from RT (luminal A hazard ratio [HR], 0.40; luminal B HR, 0.51) than high-risk subtypes (HR, 0.13); however, the overall subtype-treatment interaction term was not significant (P = .26). In an exploratory analysis of women with clinical low-risk (age older than 60 years, T1, grade 1 or 2) luminal A tumors (n = 151), 10-year IBR was 3.1% versus 11.8% for the high-risk cohort (n = 341; P = .0063). Clinical low-risk luminal A patients had a 10-year IBR of 1.3% with tamoxifen versus 5.0% with tamoxifen plus RT (P = .42). Multivariable analysis showed that RT (HR, 0.31; P < .001), clinical risk group (HR, 2.2; P = .025), and luminal A subtype (HR, 0.25; P < .001) were significantly associated with IBR. Conclusion IHC subtyping was prognostic for IBR but was not predictive of benefit from RT. Further studies may validate the exploratory finding of a low-risk luminal A group who may be spared breast RT.


2013 ◽  
Vol 7 ◽  
pp. BCBCR.S10701 ◽  
Author(s):  
Kristiina Joensuu ◽  
Marjut Leidenius ◽  
Mia Kero ◽  
Leif C. Andersson ◽  
Kathryn B. Horwitz ◽  
...  

Breast cancer can recur even decades after the primary therapy. Markers are needed to predict cancer progression and the risk of late recurrence. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), proliferation marker Ki-67, and cytokeratin CK5 were studied to find out whether their expression or occurrence in subgroups of breast cancers correlated with the time of recurrence. The expression of HER2, ER, PR, Ki-67, and CK5 was studied by IHC in 72 primary breast cancers and their corresponding recurrent/metastatic lesions. The patients were divided into three groups according to the time of the recurrence/metastasis: before two years, after 5 years, and after 10 years. Based on their IHC profiles, the tumors were divided into surrogates of the genetically defined subgroups of breast cancers and the subtype definitions were as follows: luminal A (ER or PR+HER2–), luminal B (ER or PR+HER2+), HER2 overexpressing (ER–PR–HER2+), triple-negative (ER–PR–HER2–), basal-like (ER–PR–HER2–CK5+), non-classified (ER–PR–HER2–CK5–) and luminobasal (ER or PR+CK5+). In multivariate analysis, tumor size and HER2 positivity were a significant risk of early cancer relapse. The metastases showed a significantly lower CK5 expression. CK5 positivity distinguished triple negative tumors into rapidly and slowly recurring cancers. The IHC subtype ER or PR+HER2– luminal A presented a significantly lower risk of early tumor recurrence. Ki-67 expression denoted early-relapsing tumors and correlated linearly with tumor progression, since Ki-67 positivity declined gradually from early-relapsing toward late-recurring cancers.


2010 ◽  
Vol 28 (10) ◽  
pp. 1684-1691 ◽  
Author(s):  
K. David Voduc ◽  
Maggie C.U. Cheang ◽  
Scott Tyldesley ◽  
Karen Gelmon ◽  
Torsten O. Nielsen ◽  
...  

Purpose The risk of local and regional relapse associated with each breast cancer molecular subtype was determined in a large cohort of patients with breast cancer. Subtype assignment was accomplished using a validated six-marker immunohistochemical panel applied to tissue microarrays. Patients and Methods Semiquantitative analysis of estrogen receptor (ER), progesterone receptor (PR), Ki-67, human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratin (CK) 5/6 was performed on tissue microarrays constructed from 2,985 patients with early invasive breast cancer. Patients were classified into the following categories: luminal A, luminal B, luminal-HER2, HER2 enriched, basal-like, or triple-negative phenotype–nonbasal. Multivariable Cox analysis was used to determine the risk of local or regional relapse associated the intrinsic subtypes, adjusting for standard clinicopathologic factors. Results The intrinsic molecular subtype was successfully determined in 2,985 tumors. The median follow-up time was 12 years, and there have been a total of 325 local recurrences and 227 regional lymph node recurrences. Luminal A tumors (ER or PR positive, HER2 negative, Ki-67 < 1%) had the best prognosis and the lowest rate of local or regional relapse. For patients undergoing breast conservation, HER2-enriched and basal subtypes demonstrated an increased risk of regional recurrence, and this was statistically significant on multivariable analysis. After mastectomy, luminal B, luminal-HER2, HER2-enriched, and basal subtypes were all associated with an increased risk of local and regional relapse on multivariable analysis. Conclusion Luminal A tumors are associated with a low risk of local or regional recurrence. Molecular subtyping of breast tumors using a six-marker immunohistochemical panel can identify patients at increased risk of local and regional recurrence.


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 ◽  
Author(s):  
Yen-Jen Chen ◽  
Ching-Shui Huang ◽  
Nam-Nhut Phan ◽  
Tzu-Pin Lu ◽  
Chih-Yi Liu ◽  
...  

Breast cancer intrinsic subtypes have been identified based on the transcription of a predefined gene expression (GE) profiles and algorithm (PAM50). This study compared molecular subtyping with oligonucleotide microarray and NanoString nCounter assay. A total of 109 Taiwanese breast cancers (24 with adjacent normal breast tissues) were assayed with Affymetrix Human Genome U133 plus 2.0 microarrays and 144 were assayed with the NanoString nCounter while 64 patients were assayed for both platforms. Subtyping with the nearest centroid (single sample prediction) was performed, and 16 out of 24 (67%) matched normal breasts were categorized as the normal breast-like subtype. For 64 breast cancers assayed for both platforms, 41 (65%, one unclassified by microarray) were predicted with an identical subtype, resulting in a fair Kappa statistic of 0.60. Taking nCounter subtyping as the gold standard, prediction accuracy was 43% (3/7), 81% (13/16), 25% (5/20), and 100% (20/20) for basal-like, HER2-enriched, luminal A and luminal B subtype predicted from microarray GE profiles. Microarray identified more luminal B cases from luminal A subtype predicted by nCounter. It’s not uncommon to use microarray for breast cancer molecular subtyping for research. Our study showed that fundamental discrepancy existed between distinct GE assays, and cross platform equivalence should be carefully appraised when molecular subtyping was conducted with oligonucleotide microarray.


2016 ◽  
Vol 3 (2) ◽  
pp. 47-54
Author(s):  
Wissal Mahir ◽  
Lamiaa Rouas ◽  
Driss Ferhati ◽  
Brahim Rhrab ◽  
Zaitouna Alhamany ◽  
...  

Introduction: Breast cancer remains despite the therapeutic progress, the leading cause of death by cancer among women. It represents a group of very heterogeneous clinical, histopathological and molecular diseases. Molecular heterogeneity has been demonstrated by genomic analysis, even for similar histology cancers. Four subgroups of breast carcinomas are distinguished: Luminal A, Luminal B, HER2 over expression and Basal - like. The Immuno-histo-chemical analysis useip (estrogen receptors) RE, the PR (progesterone receptors), the ((Human Epidermal Growth Factor Receptor-2), the Ki67 (proliferation marker) HER2, CK5/6) has shown a subdivision into subgroups similar to those found by genomic analysis. These subgroups are different from the point of view of clinical course and response to adjuvant treatment. Objectives: The aim of this work is to study the molecular profile of the breast cancers by immunostaining on Moroccan series to a classification with a prognostic value allowing a treatment tailored to each group of patients. Furthermore, the molecular subgroups were correlated to other clinical and histological factors. Material and methods: It is a prospective study of the laboratory of Anatomy and Pathologic cytology of the children's Hospital, the service I of the maternity hospital in Rabat and in cooperation with the United Nations Centre of pathological anatomy. To do this, 88 cases of breast cancer together were diagnosed between January 1, 2010 and December 31, 2014, taking a period of five years. All tissue samples made subject study of Immuno-histo-chemistry with the following markers: RE, PR, HER2 and Ki67. Only negative triple cases (HR and HER2 negative) benefited from an additional marking with CK5/6 and EGFR to set the basal profile. Results: Series of 88 cases of mammary carcinomas observed on operating parts, ranged in age between 28 and 84 years old, with an average of 51 ± 12, 8. Carcinoma infiltrating non-specific (DOCTORS) was the most frequent (87.5%). Ranks histo-prognostic Scarff Bloom and Richardson (SBR) 2 and 3 respectively accounted for 45.5 and 51.1% of cases and only 2, 3% of the DOCTORS were grade 1. The Luminal B (53.4%) was under the most common molecular group, followed by Luminal A (23.9%), HER2 + (15.9%) and triple negative (6.8%). The correlation of molecular type of tumors with different prognostic factors showed only one significant connection with the SBR grade.


2015 ◽  
Vol 33 (20) ◽  
pp. 2254-2261 ◽  
Author(s):  
Erica T. Warner ◽  
Rulla M. Tamimi ◽  
Melissa E. Hughes ◽  
Rebecca A. Ottesen ◽  
Yu-Ning Wong ◽  
...  

Purpose To evaluate the relationship between race/ethnicity and breast cancer–specific survival according to subtype and explore mediating factors. Patients and Methods Participants were women presenting with stage I to III breast cancer between January 2000 and December 2007 at National Comprehensive Cancer Network centers with survival follow-up through December 2009. Cox proportional hazards regression was used to compare breast cancer–specific survival among Asians (n = 533), Hispanics (n = 1,122), and blacks (n = 1,345) with that among whites (n = 14,268), overall and stratified by subtype (luminal A like, luminal B like, human epidermal growth factor receptor 2 type, and triple negative). Model estimates were used to derive mediation proportion and 95% CI for selected risk factors. Results In multivariable adjusted models, overall, blacks had 21% higher risk of breast cancer–specific death (hazard ratio [HR], 1.21; 95% CI, 1.00 to 1.45). For estrogen receptor–positive tumors, black and white survival differences were greatest within 2 years of diagnosis (years 0 to 2: HR, 2.65; 95% CI, 1.34 to 5.24; year 2 to end of follow-up: HR, 1.50; 95% CI, 1.12 to 2.00). Blacks were 76% and 56% more likely to die as a result of luminal A–like and luminal B–like tumors, respectively. No disparities were observed for triple-negative or human epidermal growth factor receptor 2–type tumors. Asians and Hispanics were less likely to die as a result of breast cancer compared with whites (Asians: HR, 0.56; 95% CI, 0.37 to 0.85; Hispanics: HR, 0.74; 95% CI, 0.58 to 0.95). For blacks, tumor characteristics and stage at diagnosis were significant disparity mediators. Body mass index was an important mediator for blacks and Asians. Conclusion Racial disparities in breast cancer survival vary by tumor subtype. Interventions are needed to reduce disparities, particularly in the first 2 years after diagnosis among black women with estrogen receptor–positive tumors.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 20-20
Author(s):  
Sandeep K. Reddy ◽  
Tara Elisabeth Seery ◽  
Christopher Szeto

20 Background: ERBB2 (HER2) is thought to be a target in <10% of CRC patients versus 20% of breast cancers, 15% of gastroesophageal cancers, and 10% of biliary cancers, based on FISH or IHC. Intrinsic molecular subtype is used to classify cancers into distinct biologic subtypes (eg. CMS 1-4 in CRC). A 50-gene qPCR assay (PAM50) identifies 5 intrinsic biological subtypes: luminal A, luminal B, HER2-enriched, basal-like, and normal-like in breast cancer. The HERACLES trial (trastuzumab plus lapatinib) resulted a 32% ORR and median TTP of 5.5 months in heavily pre-pretreated HER2+ CRC patients. We determined molecular subtypes using the 50-gene breast cancer classifier to identify an expanded CRC patient population eligible for HER2 therapy. Methods: Retrospective analysis on Whole exome (WES) DNA tumor and paired germline and matched deep whole transcriptomic sequencing (RNA-Seq) (∼200x106 reads per tumor) data from NantHealth was performed. Breast Cancer Intrinsic Subtypes based on RNAseq was used to classify CRC into 5 BC subtypes. Results: 167 CRC patients were classified using the Nant50 Breast Cancer classifier: 15.0% as Luminal B, 13.1% as Luminal A, and 1.8% as Basal-like. Surprisingly, 117/167 (70%) classified as HER2-enriched (HER-E). 15/167 (9.0%) had over-expression of ERBB2 by RNAseq or CN gain, which is consistent with published data of HER2+ CRC. ERBB2 is very significantly differentially expressed in HER2-E subtyped CRC (p=<0.001), more than ERBB2 CN gain, suggesting that HER2-E may be more HER2 driven. Across subtypes APC and TP53 were the most commonly mutated genes at 65.3% and 52.6% respectively, however both were more enriched in HER2-E CRC (APC OR=3.3, p=0.001, TP53 OR=2.6, p=0.007). Other known drivers of CRC such as PIK3CA, KRAS, and BRAF, were not differentially mutated in HER2-E CRC, however NRAS mutants were significantly more enriched in non-HER2-E CRC (OR=4.6, p=0.02). Conclusions: Even after excluding known HER2 over-expression and CN gain, PAM50-like gene classifier identifies a far higher than expected percentage of HER-E subtype CRC (99/167 = 59%) which may represent an under appreciated population for HER2 directed therapy and clinical trials.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Li Sturesdotter ◽  
Malte Sandsveden ◽  
Kristin Johnson ◽  
Anna-Maria Larsson ◽  
Sophia Zackrisson ◽  
...  

AbstractMammographic tumour appearance may provide prognostic useful information. For example, spiculation indicates invasiveness, but also better survival compared to tumours with other appearances. We aimed to study the relationship between mammographic tumour appearance and established clinicopathological factors, including surrogate molecular breast cancer subtypes, in the large Malmö Diet and Cancer Study. A total of 1116 women with invasive breast cancer, diagnosed between 1991 and 2014, were included. Mammographic tumour appearance in relation to status for oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2, histological grade, Ki67 and molecular subtype was analysed using various regression models. All models were adjusted for relevant confounders, including breast density, which can affect mammographic appearance. The results consistently showed that spiculated tumours are indicative of favourable characteristics, as they are more likely to be ER and PR positive, and more often exhibit lower histological grade and lower Ki67 expression. Furthermore, spiculated tumours tend to be of luminal A-like subtype, which is associated with a good prognosis. The establishment of associations between mammographic tumour appearance and clinico­pathological factors may aid in characterizing breast cancer at an earlier stage. This could contribute to more individualized breast cancer treatment in the future.


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