scholarly journals Bioinformatics-based analysis of TCGA to identify the prognostic biomarkers in HR-positive/HER2-negative tamoxifen-treated breast cancer

2019 ◽  
Author(s):  
Liyun Zeng ◽  
Dengjie Ouyang ◽  
Qiongyan Zou ◽  
Qitong Chen ◽  
Na Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histological Grade ◽  
Cumulative Risk ◽  
Disease Free Survival ◽  
Tamoxifen Therapy ◽  
Tamoxifen Treatment ◽  
Receptor Interaction ◽  
Breast Cancers ◽  
Clinical Factors ◽  
Disease Free

Abstract Background Patients with hormone receptor-positive (HR+) breast cancer, which accounts for approximately 70% of all breast cancers, receive tamoxifen therapy to inhibit recurrence and improve overall survival. However, the cumulative risk of distant recurrence in the past 20 years is still as high as 22 to 52% after 5 years of endotherapy. TNM stage, histological grade and age are important clinical factors related to recurrence. Differential gene analysis based on matching clinical factors will be helpful for understanding the molecular mechanism of recurrence; however, there have been no reports yet.Results In our study, we identified 647 DEGs in a TCGA dataset that included 20 patients, of which 10 patients had relapsed after tamoxifen treatment and 10 did not. Ten genes were found by the CytoHubba APP in Cytoscape. After analysis of the GO terms and KEGG pathways, we found that the genes were mainly enriched in the inflammatory response and cytokine-receptor interaction, and then these results were verified in the GEPIA2 and KM-plot websites. Finally, we identified CXCL1, CXCL2 and CX3CL1 as prognostic factors, and their overexpression in HR-positive/HER2-negative breast cancer predicted a longer disease-free survival.Conclusion In conclusion, the high expression of CXCL1, CXCL2, and CX3CL1 can predict longer disease-free survival in breast cancer after tamoxifen treatment and may be a biomarker for tamoxifen therapy.

Disease-free survival pattern in breast cancer patients in India treated in a single institution.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12030-e12030 ◽  
Author(s):  
Basavalinga S. Ajaikumar ◽  
Kodaganur Srinivasachar Gopinath ◽  
B S Srinath ◽  
Ramesh Bilimagga S ◽  
Nalini K Rao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Breast ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Distant Failure ◽  
Her 2 ◽  
Disease Free

e12030 Background: This study elucidates data from a 5 year retrospective study evaluating survival rates and prognostic factors in breast carcinoma patients in a private cancer set up in south India. Methods: 1046 patients who were treated between years 2003 to 2008 were analyzed. Clinical data including stage, histopathology type, age, node positivity, treatment plan, chemotherapy regimen, ER/ PR and Her2 Neu status, type of surgery etc were abstracted in a database. Five year disease free survival, local failure free survival and distant failure free survival was calculated using Kaplan Meier survival curves. Log rank mantel hazel tests were used to compare two survival curves. Results: Local recurrence was seen in 4% and distant metastases in 22% of the study sample. 62% of patients presented with early breast cancer (AJCC Stage I, II and IIIA). 85.6% of early and 73.1% of locally advanced breast cancers were disease free at 5 years (p<0.001).90.6% of early and 82.4% of locally advanced breast cancers had distant failure free survival at 5 years (p=0.001). Local failure free survival was 96.1% in both early and locally advanced breast disease at 5 years.94.9% of her 2 negative and 83.5% Her 2 positive were disease free at 5 years (p=0.001). 5 years progression free survival was 91.5% for breast conservation surgery vs 84.1% for mastectomy with axillary clearance (p=0.01). 75.4% with triple negative status and 80.8% non triple negative receptor status had 5 years DFS. Conclusion: This is a first report of survival patterns of breast cancer patients treated in a single centre in India. High early stage patient numbers and high median disease free survival times could be because of improvement in screening and treatment of breast cancer in a developing country like India.

Evaluation of a cytological scoring system for predicting histological grade and disease-free survival in primary breast cancer

Cytopathology ◽  
1994 ◽  
Vol 5 (5) ◽  
pp. 294-300 ◽  
Author(s):  
H. GRAAF ◽  
P. WILLEMSE ◽  
B. E. LADDÉ ◽  
H. A. BERGEN ◽  
M. KREBBER ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Scoring System ◽  
Histological Grade ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

scholarly journals Testing for HER2 in Breast Cancer: A Continuing Evolution

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Sejal Shah ◽  
Beiyun Chen
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Free Survival ◽  
Humanized Monoclonal Antibody ◽  
Epidermal Growth ◽  
Invasive Breast Carcinomas ◽  
Disease Free

Human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive factor in breast cancer. HER2 is overexpressed in approximately 15%–20% of invasive breast carcinomas and is associated with earlier recurrence, shortened disease free survival, and poor prognosis. Trastuzumab (Herceptin) a “humanized” monoclonal antibody targets the extracellular domain of HER2 and is widely used in the management of HER2 positive breast cancers. Accurate assessment of HER2 is thus critical in the management of breast cancer. The aim of this paper is to present a comprehensive review of HER2 with reference to its discovery and biology, clinical significance, prognostic value, targeted therapy, current and new testing modalities, and the interpretation guidelines and pitfalls.

Significance of chromosome 17 polysomy in breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12002-e12002
Author(s):  
Robert W. Galamaga ◽  
Rachel Mariani ◽  
Imad Almanaseer ◽  
Jacob D. Bitran
Keyword(s):  
Breast Cancer ◽  
Survival Data ◽  
Copy Number ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Chromosome 17 ◽  
Gene Copy ◽  
Breast Cancers ◽  
Her 2 ◽  
Disease Free

e12002 Background: Human epidermal growth factor receptor 2 (HER-2) overexpression occurs in up to 30% of breast cancers and has been associated with poor clinical outcomes that have improved with advances in HER-2 directed therapy. The HER-2 gene resides on the long arm of chromosome 17 and amplification is typically assessed via immunohistochemistry or fluorescence in situ hybridization (FISH); HER-2 is interpreted as amplified, non-amplified, or equivocal. The effect and clinical impact of chromosome 17 polysomy in specimens interpreted as HER-2 non-amplified has not been well-established in breast cancer patients. This subgroup may represent a unique set of patients who may benefit from HER-2 directed therapy given the increase in HER-2 gene copy number. If tumors with polysomy 17 share biologic similarities with those positive for HER-2 amplification this may significantly influence the approach to treating these patients. In a single institution study we reviewed all breast cancer cases diagnosed in 2008 which were reported as HER-2 equivocal or non-amplified via FISH and with chromosome 17 polysomy in order to extrapolate disease-free and overall survival data within this subset. Methods: HER-2 expression via FISH from patients diagnosed with breast cancer in 2008 was reviewed. In those patients with equivocal or non-amplified HER-2 expression we selected those with chromosome 17 polysomy defined as a chromosome 17 centromere copy number of > 3 per tumor cell. A total of 9 patients were identified. Results: The median age was 74 (36-88). Median tumor size was 1.6 cm (0.7-4.9) and 8 patients (88%) had both estrogen and progesterone positive tumors. Stage distribution was as follows: stage IA: 4 (44%); stage IIA: 2 (22%); stage IIB: 2 (22%) and stage IIIA: 1 (11%). The actuarial 3 year disease free survival was 67%. Conclusions: Breast cancers with equivocal or non-amplified HER-2 expression with chromosome 17 polysomy represent a unique subset of tumors with a biology that is not well-understood. Previously published studies have yielded conflicting results regarding the prognostic significance of this genotype. Our study reflects a three year survival of 67% which suggests that these patients represent an aggressive subset.

scholarly journals Expression of Bcl-2 in Breast Cancer: Correlation with Clinicopathological Characteristics and Survival

2008 ◽  
Vol 51 (2) ◽  
pp. 107-112 ◽  
Author(s):  
Filip Čečka ◽  
Helena Hornychová ◽  
Bohuslav Melichar ◽  
Aleš Ryška ◽  
Pavel Jandík ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histological Grade ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Clinical Development ◽  
Free Survival ◽  
Broad Variety ◽  
Disease Free ◽  
Common Malignancy

Breast cancer is the most common malignancy in women. It is an immensely heterogeneous disease, characterised by a broad variety of clinical development. The research in recent years has focused on finding new markers of prognosis. This study investigates the role of expression of the bcl-2 protein in breast cancer. We analysed bcl-2 expression in 57 women with primary breast carcinoma who were treated with neoadjuvant (primary) chemotherapy, followed by a surgical procedure. The bcl-2 expression was correlated with other clinicopathological characteristics of the tumour – histological grade, stage, expression of hormonal receptors, proliferation rate, and with the survival of the patients. No significant association of bcl-2 expression with either overall survival or disease free survival was found.

Prediction of long-term survival using expression of FOXA1, a determinant of estrogen response domains in breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 539-539
Author(s):  
S. Badve ◽  
D. Turbin ◽  
A. Morimiya ◽  
T. Nielsen ◽  
C. Perou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Nodal Status ◽  
Breast Cancers ◽  
Luminal A ◽  
Term Survival ◽  
Free Survival ◽  
Disease Free ◽  
Foxa1 Expression

539 Background: Recent studies have demonstrated cofactor dependency of estrogen receptor alpha (ERα) in defining specific pattern of estrogen (E2) response in breast cancer. FOXA1, also called HNF3α, a forkhead family transcription factor, has emerged as a major cofactor that is essential for optimum transcription of ∼50% of ERα:E2 responsive genes. FOXA1 is expressed in breast cancer cells and in cDNA microarray cluster analysis segregates with genes that characterize the luminal A subtype such as ERα, GATA3, and XBP-1. Detailed expression analysis of FOXA1 in human breast tumors has not been previously performed and it is not known whether it is an independent prognostic factor in breast cancer. Methods: A tissue microarray comprising tumors from 438 patients with 20 years follow-up was analyzed for FOXA1 expression using goat-anti-human FOXA1 antibody by immunohistochemistry. Percentage (P) and intensity (I) of expression was analyzed to generate numerical score (S= P × I). FOXA1 expression was correlated with tumor grade, nodal status, disease free survival, and expression of ER, PR, GATA3, HER2, p27kip1, phospho-AKT, and luminal A subtype (defined as ER &/or PR+, bcl-2+ and Her-2-neg). Results: FOXA1 expression (score greater than 100) was seen in 187 of 438 breast cancers and correlated with greater likelihood of survival at 20 year (p=0.0114). A significant positive correlation was observed between FOXA1 expression and expression of ERα (p= 0.000001), GATA3 (p= 0.000001), PR (p= 0.00001), phospho-AKT (p= 0.00001). Similarly, a significant correlation was noted with luminal A subtype. An inverse correlation was noted with tumor grade and mdm-2 expression (p=0.00001). HER2 or p27kip1 expression and nodal status showed no correlation with FOXA1. Conclusions: FOXA1 is good prognostic marker predicting disease free survival in patients with breast cancer. Since its expression correlates well with breast cancer of luminal A subtype, it can also be used to identify these good prognosis tumors from the rest of the ER positive breast cancers in archival paraffin embedded breast tissues. No significant financial relationships to disclose.

scholarly journals Expression of ER-α36, a Novel Variant of Estrogen Receptor α, and Resistance to Tamoxifen Treatment in Breast Cancer

2009 ◽  
Vol 27 (21) ◽  
pp. 3423-3429 ◽  
Author(s):  
Liang Shi ◽  
Bin Dong ◽  
Zhongwu Li ◽  
Yunwei Lu ◽  
Tao Ouyang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Tamoxifen Resistance ◽  
Disease Free Survival ◽  
Estrogen Receptor Α ◽  
Tamoxifen Treatment ◽  
Free Survival ◽  
Novel Variant ◽  
Disease Free ◽  
Disease Specific

Purpose Recently, a 36-kDa variant of estrogen receptor α (ER-α66), ER-α36, has been identified and cloned. ER-α36 predominantly localizes on the plasma membrane and in the cytoplasm and mediates a membrane-initiated “nongenomic” signaling pathway. Here, we investigate the association between ER-α36 expression and tamoxifen resistance in patients with breast cancer. Patients and Methods ER-α36 protein expression in tumors from 896 women (two independent cohorts, 1 and 2) with operable primary breast cancer was assessed using an immunohistochemistry assay. Results In the first cohort of 710 consecutive patients, overexpression of ER-α36 was associated with poorer disease-free survival (DFS) and disease-specific survival (DSS) in patients with ER-α66–positive tumors who received tamoxifen treatment (chemotherapy plus tamoxifen or tamoxifen alone, n = 307). In contrast, ER-α36 was not associated with survival in patients with ER-α66–positive tumors who did not receive tamoxifen (chemotherapy alone, n = 129) and in patients with ER-α66–negative tumors whether they received tamoxifen (n = 73) or not (n = 149). In the second cohort of 186 patients who only received tamoxifen as adjuvant therapy, overexpression of ER-α36 was significantly associated with poorer DFS and DSS in 156 ER-α66–positive patients from this cohort, and ER-α36 remained an independent unfavorable factor for both DFS and DSS in these 156 patients by a multivariate analysis (DFS: hazard ratio [HR] = 5.47; 95% CI, 1.81 to 16.51; P =. 003; DSS: HR = 13.97; 95% CI, 1.58 to 123.53; P = .018). Conclusion Women with ER-α66–positive tumors that also express high levels of ER-α36 are less likely to benefit from tamoxifen treatment.

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