scholarly journals Characterizing the Relapse Potential in Different Luminal Subtypes of Breast Cancers with Functional Proteomics

2020 ◽  
Vol 21 (17) ◽  
pp. 6077
Author(s):  
Tung-Yi Lin ◽  
Pei-Wen Wang ◽  
Chun-Hsun Huang ◽  
Pei-Ming Yang ◽  
Tai-Long Pan
Keyword(s):  
Breast Cancer ◽  
Cathepsin D ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Term Survival ◽  
Luminal B ◽  
Functional Roles ◽  
The Matrix

Poor prognosis due to the high relapse and metastasis rates of breast cancer has been particularly linked to the luminal B subtype. The current study utilized MCF-7 and ZR-75-1 to investigate various luminal subtypes of breast cancers that have discrepant expressions in the estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Understanding of the differential protein profiles and the associated pathways could help alleviate the malignance and promote the long-term survival rate of breast cancer patients. Functional proteome tools were applied to comprehensively delineate the global protein alterations that reflect the varieties of biological features between the two subtypes. In this study, a total of 11 proteins with significant and meaningful changes were identified. These protein targets including PRX2, CK19, nucleophosmin and cathepsin D were mostly involved in cell differentiation or proliferation. Particularly, cathepsin D was highly expressed in the luminal B subtype. Moreover, the level of cathepsin-D was also upregulated in the clinical metastatic tissues. Accordingly, the RNA interference-mediated silencing of cathepsin D stimulated ER expression but suppressed the level of HER2. The knockdown of cathepsin D enhanced the level of ZO-1 and a remarkable decrease in N-cadherin was also detected. Again, the matrix metalloproteinases (MMP) activity was impaired under the cathepsin D abolishment. Collectively, this study represented a modality to explore novel relationships in a proteome complex and highlighted the functional roles of cathepsin D in treatment options for different subtypes of breast cancer.

HER-2-Amplified Breast Cancer

2018 ◽  
Author(s):  
Zahraa Al-Hilli ◽  
Judy C Boughey
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Breast Cancers ◽  
Aggressive Disease ◽  
Node Positive Disease ◽  
Her 2 ◽  
Epidermal Growth ◽  
Positive Breast Cancer

Amplification of the human epidermal growth factor receptor–2 (HER-2) gene is found in approximately 15 to 30% of breast cancers. Historically, HER-2 overexpression has been associated with aggressive disease and a poor prognosis. However, the use of targeted anti-HER2 therapy has revolutionized the treatment of HER-2-positive disease, and the use of the monoclonal antibody trastuzumab in combination with chemotherapy is now standard of care for tumors greater than 1 cm in size and in node-positive disease. More recently, the value of dual-agent anti-HER-2 therapy has been demonstrated in large clinical trials. This review provides an overview of HER-2-positive breast cancer, its molecular basis, methods of identification, and treatment options and strategies. This review contains 2 figures and 70 references Key words: anti-HER-2 therapy, breast cancer, HER-2-positive breast cancer, HER-2 resistance, lapatinib, neoadjuvant chemotherapy, pertuzumab, small HER-2-positive breast cancer, trastuzumab

scholarly journals ER, PR, HER2, Ki-67 and CK5 in Early and Late Relapsing Breast Cancer—Reduced CK5 Expression in Metastases

2013 ◽  
Vol 7 ◽  
pp. BCBCR.S10701 ◽  
Author(s):  
Kristiina Joensuu ◽  
Marjut Leidenius ◽  
Mia Kero ◽  
Leif C. Andersson ◽  
Kathryn B. Horwitz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative ◽  
Significant Risk ◽  
Growth Factor Receptor ◽  
Primary Therapy ◽  
Breast Cancers ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B

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.

scholarly journals Performing Data Mining to Explain the Correlation between the BIRC5 Gene and Prognosis in Breast Cancer Patients

2020 ◽  
Author(s):  
Hong Dongsheng ◽  
Zhang YanFang ◽  
Ye Ziqi ◽  
Chen Jing ◽  
Lu Xiaoyang
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Cancer Cell Line ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Luminal B ◽  
Kaplan Meier ◽  
Er Positive

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.

α-basic-crystallin expression in basal-like breast cancer and its association with brain metastasis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1025-1025
Author(s):  
H. F. Kennecke ◽  
D. Voduc ◽  
S. Leung ◽  
V. L. Cryns ◽  
C. M. Perou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastasis ◽  
Metastatic Disease ◽  
Distant Metastasis ◽  
Growth Factor Receptor ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Chi Square ◽  
Ki 67 ◽  
Cancer Subtypes

1025 Background: Basal-like breast cancers are high grade tumors with poor prognosis, having propensity for brain and lung metastasis (Perou et al. Nature 406:747–52, 2000, Cheang et al. Clin Cancer Res 14:1368–76, 2008, Luck et al. Clin Oncol (R Coll Radiol) 20:40–5, 2008). α-basic-crystallin (αBC), a small heat shock protein with anti-apoptotic and oncogenic activity, is expressed in about half of basal-like breast cancers but only 6% of other types (Moyano et al. J Clin Invest 116:261–70, 2006). Here we investigate the association of αBC with sites of distant metastasis in a large cohort of breast cancer patients. Methods: Our cohort consists of 4046 early invasive breast cancers referred to the British Columbia Cancer Agency from 1986 to 1992. Archival paraffin tissue blocks were used to construct tissue microarrays. Breast cancer subtypes were defined using a surrogate of six immunohistochemical markers: ER, PR, HER2, Ki-67, epidermal growth factor receptor and cytokeratin 5/6. αBC immunostaining was scored by pre-established, published criteria. All documented sites of distant metastasis were abstracted by chart review according to predefined categories. The null hypothesis was tested using chi-square and Fisher's Exact tests; all tests were two-sided. Results: Among 3,248 cases with interpretable αBC data, 11% were αBC +. Among patients who developed distant metastatic disease, the 10-yr BCSS survival in αBC+ and - tumors was 12% and 29%. Sites of metastatic disease included: brain (15%), lung (35%), liver (35%) and bone (65%). Brain metastasis was significantly more common among αBC positive tumors (Fisher's Exact test p<10e-8). Basal-like tumors with brain metastasis commonly co-expressed αBC (Chi-square p=0.006). Conclusion: αBC is significantly associated with brain metastasis, particularly among basal breast cancers. These findings suggested that αBC may be involved in tumor cell metastasis and may allow early identification of a subset of patients at particularly high risk of brain metastasis. [Table: see text] No significant financial relationships to disclose.

scholarly journals 8p11.23 Amplification in Breast Cancer: Molecular Characteristics, Prognosis and Targeted Therapy

2020 ◽  
Vol 9 (10) ◽  
pp. 3079 ◽  
Author(s):  
Ioannis A. Voutsadakis
Keyword(s):  
Breast Cancer ◽  
Transcription Initiation ◽  
Zinc Finger Protein ◽  
Growth Factor Receptor ◽  
Initiation Factor ◽  
Molecular Characteristics ◽  
Breast Cancers ◽  
Free Survival ◽  
Luminal B ◽  
Over Expression

Background: Amplification of the locus 8p11.23 has been observed in cancer and genes of this locus, including ZNF703 (Zinc finger protein 703), NSD3 (Nuclear receptor binding SET domain protein 3) and FGFR1 (Fibroblast growth factor receptor 1), have been put forward as dominant oncogenes conferring pathophysiologic benefit in cancers with amplifications. However, there is no consensus on the importance of each of them or any other genes of the amplicon or even a consensus on which genes are part of the amplicon. Methods: Publicly available data were used to characterize the locus amplified at 8p11.23 and derive information on each of the genes and roles as oncogenes. The frequency of the amplifications in the locus was examined in the cBioportal platform, and expression levels of the amplicon genes in amplified cases were derived from genomic studies reported in the platform. Examination of the influence of mRNA expressions of each gene of the locus for Recurrence-free survival in breast cancer was performed using K-M plotter. Results: The 8p11.23 amplicon is present in higher frequency in squamous cell lung carcinomas, breast cancers and bladder carcinomas and is only rarely observed in other cancers. The most frequently amplified genes within the amplicon vary between different types of cancers. In breast cancer, amplified cases are most commonly of the luminal B type. Amplified genes are not always over-expressed and there is a low correlation of amplification with over-expression in amplicon genes with variation between genes. The presence of the amplicon does not influence the aneuploidy score or the tumor mutation burden of breast cancers. Regarding prognosis, the two genes of the amplicon whose mRNA hyper-expression portends adverse relapse-free survival in breast cancer are EIF4EBP1 (Eukaryotic transcription initiation factor 4E binding protein 1) and LSM1 (LSM1 homolog, mRNA degradation associated). Conclusion: Besides the previously proposed genes to play a role as dominant oncogenes in the 8p11.23 cancer amplified locus, other genes may also be important in breast cancer based on the high correlation of their amplification and mRNA expression and adverse prognosis conferred by over-expression, consistent with an oncogenic role.

scholarly journals Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer

2013 ◽  
Vol 20 (3) ◽  
pp. 339-348 ◽  
Author(s):  
Sewha Kim ◽  
Do Hee Kim ◽  
Woo-Hee Jung ◽  
Ja Seung Koo
Keyword(s):  
Breast Cancer ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Glutamine Metabolism ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Luminal B ◽  
Related Proteins ◽  
Glutaminase 1

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.

scholarly journals Disease-free Probability and Triple-Negative Breast Cancer

2012 ◽  
Vol 35 (1) ◽  
pp. 5-13
Author(s):  
Prakasit Chirappapha ◽  
Thongchai Sukarayothin ◽  
Yodying Wasuthit ◽  
Ronnarat Suvikapalornkul ◽  
Panuwat Lertsithichai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Local Recurrence ◽  
Triple Negative Breast Cancer ◽  
Distant Metastasis ◽  
Triple Negative ◽  
Free Probability ◽  
Growth Factor Receptor ◽  
Tumor Stage ◽  
Breast Cancers ◽  
Breast Cancer Patients

Objective: To compare the probabilities of local recurrence and distant metastasis between women with triple-negative and non- triple negative breast cancers. Methods: Medical and pathological records of breast cancer patients treated between the years 2002 and 2006 were reviewed. Results: There were 256 patients with complete data on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) expression determinations. There were 54 patients (21%) with triple-negative (ER-, PR-, HER2 -) cancers. Triple-negative patients were more likely to have larger tumors with higher histologic grade. The median fallow-up time was 4 years. The probabilities of local and distant recurrence were similar between the two groups of patients. Only two factors were independently and significantly associated with overall recurrence: tumor stage and tumor size. Conclusion: Triple-negative breast cancer did not have a higher risk for both local recurrence and distant metastasis when compared with non-triple negative cancer.

scholarly journals Long-term Survival of Patients with Breast Cancer and Brain Metastases: ‘The experience of the 2nd Oncology Department of Metropolitan Hospital and a brief review of the literature’

2015 ◽  
Vol 6 (1) ◽  
pp. 18-26
Author(s):  
Aravantinou-Fatorou E ◽  
Skarlos D ◽  
Klouvas G ◽  
Galani E ◽  
Christodoulou C.
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Cancer Patients ◽  
Median Time ◽  
Metastatic Disease ◽  
Cancer Type ◽  
Breast Cancer Patients ◽  
Cns Metastases ◽  
Term Survival ◽  
Luminal B

Abstract Background: Novel therapeutic approaches and new compounds during the last decade have prolonged survival of breast cancer patients with metastatic disease, resulting in higher incidence of central nervous system (CNS) metastases. Many of these patients live longer than expected. Patients and methods: We reviewed breast cancer patients with brain metastases from our department, living longer than 1 year. Our purposes were to present patient and treatment characteristics and correlate them with disease outcome. Moreover, we aimed at reviewing the current literature. Results: We detected 20 women with brain metastases from breast cancer, living longer than 1 year. The mean age was 41 years (range 22-61 years). One (5%) woman had luminal A breast cancer type, four (20%) patients had luminal B and HER2 negative, nine (45%) patients luminal B and HER2 positive, four (20%) patients HER2 enriched and two (10%) patients had triple-negative breast cancer. Most of them (70%) had infiltrating ductal histological type and grade 3. Moreover, the majority had known metastatic disease when brain metastases appeared. The most common sites of disease were lung, liver and bone. Median time from breast cancer diagnosis until the presence of CNS metastases was 44 months (range 6-204 months). The progression free survival (PFS) of the most chemotherapeutic schedules was according to the literature. However, PFS of some compounds exceeded all expectations. Median time of survival was 25 months (range 13-116 months). Ten patients are still alive, having achieved a median survival rate of 35 months (range 17-78 months). Conclusion: The combination of surgery, radiotherapy, chemotherapy and anti HER2 treatments is at present the best way to extend the OS and improve the quality of life of breast cancer patients with brain metastases. Prognostic markers for assessing brain metastases are required. Application of prophylactic treatment for these patients is under consideration.

scholarly journals Breast Cancer Molecular Subtypes Among Moroccan Women

2016 ◽  
Vol 3 (2) ◽  
pp. 47-54
Author(s):  
Wissal Mahir ◽  
Lamiaa Rouas ◽  
Driss Ferhati ◽  
Brahim Rhrab ◽  
Zaitouna Alhamany ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Genomic Analysis ◽  
Molecular Profile ◽  
Molecular Heterogeneity ◽  
Breast Cancers ◽  
Luminal A ◽  
Tissue Samples ◽  
Luminal B ◽  
Molecular Group

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.

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