scholarly journals Mammographic tumour appearance is related to clinicopathological factors and surrogate molecular breast cancer subtype

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Li Sturesdotter ◽  
Malte Sandsveden ◽  
Kristin Johnson ◽  
Anna-Maria Larsson ◽  
Sophia Zackrisson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Subtype ◽  
Histological Grade ◽  
Breast Cancer Subtype ◽  
Growth Factor Receptor ◽  
Good Prognosis ◽  
Clinicopathological Factors ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Epidermal Growth

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.

scholarly journals Low KIBRA Expression Is Associated with Poor Prognosis in Patients with Triple-Negative Breast Cancer

Medicina ◽  
2021 ◽  
Vol 57 (8) ◽  
pp. 837
Author(s):  
So-Woon Kim ◽  
Jinah Chu ◽  
Sung-Im Do ◽  
Kiyong Na
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Histological Grade ◽  
Growth Factor Receptor ◽  
Hippo Signaling ◽  
Luminal A ◽  
Luminal B ◽  
Epidermal Growth

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.

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

2020 ◽  
Author(s):  
Amit Kumar Sinha ◽  
Amrita Ghosh
Keyword(s):  
Breast Cancer ◽  
Therapeutic Response ◽  
Molecular Subtype ◽  
Growth Factor Receptor ◽  
Normal Breast ◽  
Breast Cancers ◽  
Luminal A ◽  
Luminal B ◽  
Molecular Subclass ◽  
Epidermal Growth

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.

Recent progress in immunotherapy of breast cancer targeting the human epidermal growth factor receptor 2 (HER2)

2021 ◽  
pp. 107815522199163
Author(s):  
Homa Seyedmirzaei ◽  
Mahsa Keshavarz-Fathi ◽  
Sepideh Razi ◽  
Masoumeh Gity ◽  
Nima Rezaei
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
New Drugs ◽  
Breast Cancers ◽  
Cancer Subtypes ◽  
Drug Conjugates ◽  
Heavy Burden ◽  
Epidermal Growth

Objective Breast cancer is responsible for most of the cancer-induced deaths in women around the world. The current review will discuss different approaches of targeting HER2, an epidermal growth factor overexpressed in 30% of breast cancer cases. Data sources We conducted a search on Pubmed and Scopus databases to find studies relevant to HER2+ breast cancers and targeting HER2 as means of immunotherapy. Out of 1043 articles, 105 studies were included in this review. Data summary As well as the introduction of HER2 and breast cancer subtypes, we discussed various aspects of HER2-targeting immunotherapy including monoclonal antibodies, Antibody-drug conjugates (ADCs), Chimeric Antigen Receptor (CAR) T-cells and vaccines. Conclusions Despite several ways of controlling breast cancer, the need to investigate new drugs and approaches seems to be much significant as this cancer still has a heavy burden on people’s health and survival.

Breast Cancer Prognosis: A Genetic Code for Personalized Therapy

2021 ◽  
Author(s):  
Antonio Rulli ◽  
Laura Fortuna ◽  
Svitlana Zayik ◽  
Piero Covarelli ◽  
Fabrizio Stracci ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Subtype ◽  
Rna Extraction ◽  
Diagnostic Category ◽  
Good Prognosis ◽  
Personalized Therapy ◽  
Cancer Prognosis ◽  
Luminal A ◽  
Biological Behaviour ◽  
Disease Recovery

Abstract Background: Breast cancer is distinguished in three different subtypes, based on clinical and molecular parameters: Luminal - HER2 - Basal type. Luminal carcinomas (which represent about 65% of the total) are distinguished by a particular heterogeneity of biological behaviour with disease recovery in about 40-50% and death in about two-thirds of these patients at 5 years from diagnosis, despite initial anatomopathological pictures of apparent low aggressiveness. Precisely, more biomolecular parameters are desirable for this diagnostic category which starting from an estimated disease recovery can guide therapeutic choices in a more articulated way that is modelled on the actual needs.Method: The aim of this work is to build a panel of genes that can be used to personalize therapy and consequently reduce mortality. Our kit is patented and includes 33 genes that best characterize neoplastic heterogeneity and sensitivity to drugs. The study involved the total transcriptome (RNA) sequencing of 40 patient samples carried out in the two-year period 1994/1995 with the aim of identifying a group of genes expressed differentially among patients with good prognosis and those with poor prognosis. Results: Total RNA extraction from formalin-fixed, paraffin-embedded samples and then Library preparation for RNA-Seq was achieved. The study highlighted some genes: CXCL13 life gene, IFITM10 death gene always present regardless of molecular subtype, and DSCAM-AS1 gene, specific for Luminal A subtype, that if present, let the patient avoid standard PBI and neoadjuvant therapy. Conclusion: The goal is to implement a different surgical and adjuvant personalized therapy for every single patient.

TP53 Germline Mutations are Associated with HR+/HER2+ in BRCA1/2-Negative Early-Onset Breast Cancer in China

2022 ◽  
Author(s):  
Lili Chen ◽  
Meng Huang ◽  
Minyan Chen ◽  
Yuxiang Lin ◽  
Jing Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Onset ◽  
Tp53 Mutation ◽  
Sporadic Breast Cancer ◽  
Molecular Subtype ◽  
Growth Factor Receptor ◽  
Early Onset Breast Cancer ◽  
Her 2 ◽  
Epidermal Growth ◽  
The Relationship

Abstract Background: Except for BRCA1/2, there is no data on the relationship between genetic counseling for the range of mutations and early-onset breast cancer populations. We looked for a link between inherited genes and the molecular subtype of early-onset breast cancer.Methods: We genotyped 1214 individuals with early-onset sporadic breast cancer (age≤40 years) who were BRCA1/2-negative in 3 genes: TP53, PALB2, and RECQL. We focus on the immunohistochemistry characteristics that are unique to each patient. Results: The mutation rates of TP53, PALB2, and RECQL in 1214 BRCA-negative young individuals were 4/1214(0.33%), 8/1214(0.66%), 2/1214(0.16%), respectively. The fact that the TP53 mutation rate was 3.49% among estrogen receptor-and/or progesterone receptor-positive, human epidermal growth factor receptor 2 (HER-2) amplification patients under the age of 35 (P<0.001) was particularly noteworthy. Conclusion: According to the findings, TP53 genetic testing should focus on women under 35 with HR-positive and HER2-positve IDC patients.

scholarly journals Response to Radiotherapy After Breast-Conserving Surgery in Different Breast Cancer Subtypes in the Swedish Breast Cancer Group 91 Radiotherapy Randomized Clinical Trial

2017 ◽  
Vol 35 (28) ◽  
pp. 3222-3229 ◽  
Author(s):  
Martin Sjöström ◽  
Dan Lundstedt ◽  
Linda Hartman ◽  
Erik Holmberg ◽  
Fredrika Killander ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Breast Conservation ◽  
Growth Factor Receptor ◽  
Low Risk ◽  
Breast Conservation Surgery ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Cancer Group ◽  
Breast Cancer Group

Purpose To evaluate the effect of adjuvant radiotherapy (RT) after breast conservation surgery in different breast cancer subtypes in a large, randomized clinical trial with long-term follow-up. Patients and Methods Tumor tissue was collected from 1,003 patients with node-negative, stage I and II breast cancer who were randomly assigned in the Swedish Breast Cancer Group 91 Radiotherapy trial between 1991 and 1997 to breast conservation surgery with or without RT. Systemic adjuvant treatment was sparsely used (8%). Subtyping was performed with immunohistochemistry and in situ hybridization on tissue microarrays for 958 tumors. Results RT reduced the cumulative incidence of ipsilateral breast tumor recurrence (IBTR) as a first event within 10 years for luminal A–like tumors (19% v 9%; P = .001), luminal B–like tumors (24% v 8%; P < .001), and triple-negative tumors (21% v 6%; P = .08), but not for human epidermal growth factor receptor 2–positive (luminal and nonluminal) tumors (15% v 19%; P = .6); however, evidence of an overall difference in RT effect between subtypes was weak ( P = .21). RT reduced the rate of death from breast cancer (BCD) for triple-negative tumors (hazard ratio, 0.35; P = .06), but not for other subtypes. Death from any cause was not improved by RT in any subtype. A hypothesized clinical low-risk group did not have a low risk of IBTR without RT, and RT reduced the rate of IBTR as a first event after 10 years (20% v 6%; P = .008), but had no effect on BCD or death from any cause. Conclusion Subtype was not predictive of response to RT, although, in our study, human epidermal growth factor receptor 2–positive tumors seemed to be most radioresistant, whereas triple-negative tumors had the largest effect on BCD. The effect of RT in the presumed low-risk luminal A–like tumors was excellent.

Epigenetic aspects of triple-negative in patients with breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1041-1041
Author(s):  
Joaquina Martínez-Galan ◽  
Sandra Rios ◽  
Juan Ramon Delgado ◽  
Blanca Torres-Torres ◽  
Jesus Lopez-Peñalver ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Dna Methylation ◽  
Triple Negative ◽  
Breast Cancer Subtype ◽  
Regulation Of Gene Expression ◽  
Breast Cancer Subtypes ◽  
Luminal A ◽  
Cancer Subtypes ◽  
Luminal B

1041 Background: Identification of gene expression-based breast cancer subtypes is considered a critical means of prognostication. Genetic mutations along with epigenetic alterations contribute to gene-expression changes occurring in breast cancer. However, the reproducibility of differential DNA methylation discoveries for cancer and the relationship between DNA methylation and aberrant gene expression have not been systematically analysed. The present study was undertaken to dissect the breast cancer methylome and to deliver specific epigenotypes associated with particular breast cancer subtypes. Methods: By using Real Time QMSPCR SYBR green we analyzed DNA methylation in regulatory regions of 107 pts with breast cancer and analyzed association with prognostics factor in triple negative breast cancer and methylation promoter ESR1, APC, E-Cadherin, Rar B and 14-3-3 sigma. Results: We identified novel subtype-specific epigenotypes that clearly demonstrate the differences in the methylation profiles of basal-like and human epidermal growth factor 2 (HER2)-overexpressing tumors. Of the cases, 37pts (40%) were Luminal A (LA), 32pts (33%) Luminal B (LB), 14pts (15%) Triple-negative (TN), and 9pts (10%) HER2+. DNA hypermethylation was highly inversely correlated with the down-regulation of gene expression. Methylation of this panel of promoter was found more frequently in triple negative and HER2 phenotype. ESR1 was preferably associated with TN(80%) and HER2+(60%) subtype. With a median follow up of 6 years, we found worse overall survival (OS) with more frequent ESR1 methylation gene(p>0.05), Luminal A;ESR1 Methylation OS at 5 years 81% vs 93% when was ESR1 Unmethylation. Luminal B;ESR1 Methylation 86% SG at 5 years vs 92% in Unmethylation ESR1. Triple negative;ESR1 Methylation SG at 5 years 75% vs 80% in unmethylation ESR1. HER2;ESR1 Methylation SG at 5 years was 66.7% vs 75% in unmethylation ESR1. Conclusions: Our results provide evidence that well-defined DNA methylation profiles enable breast cancer subtype prediction and support the utilization of this biomarker for prognostication and therapeutic stratification of patients with breast cancer.

Management of early-stage breast cancer: Are we headed in the right direction?

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 284-284
Author(s):  
U. Zurawska ◽  
D. A. Baribeau ◽  
C. Victor ◽  
S. Giilck ◽  
A. Florescu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Histological Grade ◽  
Growth Factor Receptor ◽  
Early Stage Breast Cancer ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Excellent Outcome ◽  
Hormone Receptor Positive ◽  
The Right

284 Background: The understanding of breast cancer (BC) as a heterogeneous disease consisting of distinct subtypes based on variation in expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) has led to more personalized treatment. We postulated that with increased adoption of chemotherapy and targeted therapy for HER2 positive patients, the outcomes of ER/PR+, HER2- and of HER2+ subtypes of breast cancer would be similar. Methods: A chart review was performed of female patients >18 years old seen by a medical oncologist at an academic cancer centre in Toronto, Canada, between January 1, 2005 and December 31, 2006, for stage I-III invasive breast cancer. Clinical features, 5-year overall (OS) and relapse-free survival (RFS) of three BC subtypes were compared: ER/PR+, HER2- (hormone receptor positive, HR), HER2+ (HER2), and ER/PR-, HER2- (triple negative, TN). Results: Of 870 patient charts reviewed, 525 were analysed. There were 341 HR, 101 HER2 and 83 TN patients. TN patients were younger (p<0.001), and had higher stage (p<0.001) and higher histological grade tumors (p<0.001). The 5-year RFS and OS were: HR: 88.2% and 96.6%, HER2: 76.7% and 92%, TN: 79.8% and 83.9%. Chemotherapy was used in 41.1%, 84.2% and 83.1% of HR, HER2 and TN patients. Anthracycline plus taxane regimens were used in 48.6%, 52.9% and 68.1% of HR, HER2 and TN patients, respectively. Among HER2 patients, only 74.3% received trastuzumab. The 5-year RFS and OS for HER2 patients who received trastuzumab were 79.9% and 91.8%, and for those who did not: 69% and 91.6%. Conclusions: HR+ patients have an excellent outcome. Despite significant improvement in outcomes of HER2+ patients with early stage breast cancer, they still remain at higher risk of recurrence along with TN patients. Trastuzumab was underutilized among HER2+ patients in this cohort, which may have contributed to decreased 5 year RFS. Ongoing prospective follow up of early BC outcomes by breast cancer subtypes is important.

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