ESR1 gene amplification and protein expression in 946 patients with resected breast cancer: A Hellenic Cooperative Oncology Group (HeCOG) translational research study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 592-592
Author(s):  
George E. Pentheroudakis ◽  
Anna Batistatou ◽  
Urania Dafni ◽  
Mattheos Bobos ◽  
Eleftheria Tsolaki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Gene Amplification ◽  
Cox Regression ◽  
Phase Iii ◽  
Gene Gain ◽  
Clinicopathologic Characteristics ◽  
Cox Regression Analysis ◽  
Allred Score ◽  
Esr1 Gene

592 Background: Discrepant data have been reported on the incidence of ESR1 gene amplification in breast cancer, its correlation to clinicopathologic characteristics and its impact on prognosis. Methods: Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 946 patients participating in two adjuvant chemotherapy phase III trials (HE10/97 and HE10/00) were centrally assessed in tissue microarrays by immunohistochemistry (IHC) for estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2). FISH was also performed for HER2, TOP2A and ESR1 using commercially available dual (for ESR1) and triple (for HER2 and TOP2A) hybridization probes. Results: The majority of patients had >T2 (69%), node-positive, ER-positive (>1% stained cells, 73%) tumors managed with resection, chemotherapy and hormonotherapy (76%). Only 38 tumors (4.0%) had ESR1 gene amplification (ESR1/CEN6 ratio >2) and 514 (54.3%) ESR1 gene gain (1<ratio<2). The number of ESR1 gene copies was 3-4 in 251 (26.5%) and 5-10 in 42 (4.4%) of cases. HER2 and TOP2A gene amplification was seen in 234 (25.3%) and 101 (10.9%) of tumors, respectively. We studied the immunohistochemical expression of ER protein by evaluating the percentage of stained cells, the Allred score (0-2, 26.8%; 3-6, 62.5%; 7-8, 10.7% of tumors) and the semiquantitative H-Score (50-100, 13.8%; 101-200, 36.8%; 201-300, 15% of tumors). ESR1 gene amplification was significantly associated with taxane therapy, age >50, postmenopausal status, grade III-IV, absence of HER2 amplification and ER protein expression (p<0.05). At a median follow-up of 92 months, univariate Cox regression analysis showed that ER protein expression, but not ESR1 gene status, was a predictor of favorable outcome. In multivariate analysis, tumor size >5 cm, >4 involved nodes and negative/low ER protein expression by Allred score were independent adverse prognostic factors. Conclusions: Our data showed a rather low incidence of ESR1 gene amplification and failed to confirm its prognostic/predictive utility. ESR1 mRNA expression data will be presented at the meeting.

scholarly journals Randomized Phase III Trial of Ixabepilone Plus Capecitabine Versus Capecitabine in Patients With Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane

2010 ◽  
Vol 28 (20) ◽  
pp. 3256-3263 ◽  
Author(s):  
Joseph A. Sparano ◽  
Eduard Vrdoljak ◽  
Oliver Rixe ◽  
Binghe Xu ◽  
Alexey Manikhas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cox Regression ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Previously Treated

PurposeWe sought to determine whether the combination of ixabepilone plus capecitabine improved overall survival (OS) compared with capecitabine alone in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes.Patients and MethodsA total of 1,221 patients with MBC previously treated with anthracycline and taxanes were randomly assigned to ixabepilone (40 mg/m2intravenously on day 1) plus capecitabine (2,000 mg/m2orally on days 1 through 14) or capecitabine alone (2,500 mg/m2on the same schedule) given every 21 days. The trial was powered to detect a 20% reduction in the hazard ratio (HR) for death.ResultsThere was no significant difference in OS between the combination and capecitabine monotherapy arm, the primary end point (median, 16.4 v 15.6 months; HR = 0.9; 95% CI, 078 to 1.03; P = .1162). The arms were well balanced with the exception of a higher prevalence of impaired performance status (Karnofsky performance status 70% to 80%) in the combination arm (32% v 25%). In a secondary Cox regression analysis adjusted for performance status and other prognostic factors, OS was improved for the combination (HR = 0.85; 95% CI, 0.75 to 0.98; P = .0231). In 79% of patients with measurable disease, the combination significantly improved progression-free survival (PFS; median, 6.2 v 4.2 months; HR = 0.79; P = .0005) and response rate (43% v 29%; P < .0001). Grade 3 to 4 neuropathy occurred in 24% treated with the combination, but was reversible.ConclusionThis study confirmed a previous trial demonstrating improved PFS and response for the ixabepilone-capecitabine combination compared with capecitabine alone, although this did not result in improved survival.

scholarly journals Identification and development of an independent immune-related genes prognostic model for breast cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lin Chen ◽  
Yuxiang Dong ◽  
Yitong Pan ◽  
Yuhan Zhang ◽  
Ping Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
Risk Scores ◽  
Validation Dataset ◽  
Immune Gene ◽  
Cox Regression Analysis ◽  
Immune Genes ◽  
Immune Related Genes

Abstract Background Breast cancer is one of the main malignant tumors that threaten the lives of women, which has received more and more clinical attention worldwide. There are increasing evidences showing that the immune micro-environment of breast cancer (BC) seriously affects the clinical outcome. This study aims to explore the role of tumor immune genes in the prognosis of BC patients and construct an immune-related genes prognostic index. Methods The list of 2498 immune genes was obtained from ImmPort database. In addition, gene expression data and clinical characteristics data of BC patients were also obtained from the TCGA database. The prognostic correlation of the differential genes was analyzed through Survival package. Cox regression analysis was performed to analyze the prognostic effect of immune genes. According to the regression coefficients of prognostic immune genes in regression analysis, an immune risk scores model was established. Gene set enrichment analysis (GSEA) was performed to probe the biological correlation of immune gene scores. P < 0.05 was considered to be statistically significant. Results In total, 556 immune genes were differentially expressed between normal tissues and BC tissues (p < 0. 05). According to the univariate cox regression analysis, a total of 66 immune genes were statistically significant for survival risk, of which 30 were associated with overall survival (P < 0.05). Finally, a 15 immune genes risk scores model was established. All patients were divided into high- and low-groups. KM survival analysis revealed that high immune risk scores represented worse survival (p < 0.001). ROC curve indicated that the immune genes risk scores model had a good reliability in predicting prognosis (5-year OS, AUC = 0.752). The established risk model showed splendid AUC value in the validation dataset (3-year over survival (OS) AUC = 0.685, 5-year OS AUC = 0.717, P = 0.00048). Moreover, the immune risk signature was proved to be an independent prognostic factor for BC patients. Finally, it was found that 15 immune genes and risk scores had significant clinical correlations, and were involved in a variety of carcinogenic pathways. Conclusion In conclusion, our study provides a new perspective for the expression of immune genes in BC. The constructed model has potential value for the prognostic prediction of BC patients and may provide some references for the clinical precision immunotherapy of patients.

scholarly journals The Investigation of Associations between TP53 rs1042522, BBC3 rs2032809, CCND1 rs9344, EGFR rs2227983 Polymorphisms and Breast Cancer Phenotype and Prognosis

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1419
Author(s):  
Justina Bekampytė ◽  
Agnė Bartnykaitė ◽  
Aistė Savukaitytė ◽  
Rasa Ugenskienė ◽  
Erika Korobeinikova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Cox Regression ◽  
Cancer Prognosis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Cox Regression Analysis ◽  
Pcr Rflp ◽  
Oncological Diseases ◽  
Cancer Phenotype

Breast cancer is one of the most common oncological diseases among women worldwide. Cell cycle and apoptosis—related genes TP53, BBC3, CCND1 and EGFR play an important role in the pathogenesis of breast cancer. However, the roles of single nucleotide polymorphisms (SNPs) in these genes have not been fully defined. Therefore, this study aimed to analyze the association between TP53 rs1042522, BBC3 rs2032809, CCND1 rs9344 and EGFR rs2227983 polymorphisms and breast cancer phenotype and prognosis. For the purpose of the analysis, 171 Lithuanian women were enrolled. Genomic DNA was extracted from peripheral blood; PCR-RFLP was used for SNPs analysis. The results showed that BBC3 rs2032809 was associated with age at the time of diagnosis, disease progression, metastasis and death. CCND1 rs9344 was associated with tumor size, however an association resulted in loss of significance after Bonferroni correction. In survival analysis, significant associations were observed between BBC3 rs2032809 and OS, PFS and MFS. EGFR rs2227983 also showed some associations with OS and PFS (univariate Cox regression analysis). However, the results were in loss of significance (multivariate Cox regression analysis). In conclusion, BBC3 rs2032809 polymorphism was associated with breast cancer phenotype and prognosis. Therefore, it could be applied as potential markers for breast cancer prognosis.

Her-2/neu Gene Amplification and Protein Expression in Primary Male Breast Cancer

2004 ◽  
Vol 84 (3) ◽  
pp. 215-223 ◽  
Author(s):  
Christian Rudlowski ◽  
Nicolaus Friedrichs ◽  
Andree Faridi ◽  
Lazlo Füzesi ◽  
Roland Moll ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Gene Amplification ◽  
Male Breast Cancer ◽  
Male Breast ◽  
Her 2 ◽  
Primary Male

Expression of BCL2L12, a new member of apoptosis-related genes, in breast tumors

2003 ◽  
Vol 89 (06) ◽  
pp. 1081-1088 ◽  
Author(s):  
Maroulio Talieri ◽  
Eleftherios Diamandis ◽  
Nikos Katsaros ◽  
Dimitrios Gourgiotis ◽  
Andreas Scorilas
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Cox Regression ◽  
Breast Tumors ◽  
Cell Types ◽  
Research Society ◽  
Genetic Alterations ◽  
Cox Regression Analysis ◽  
Reverse Transcription Pcr ◽  
Lower Stage

SummaryApoptosis, a normal physiological form of cell death, is critically involved in the regulation of cellular homeostasis. If the delicate balance between cell death and cell proliferation is altered by a defect in the normal regulation of apoptosis signaling, a cell population is able to survive and accumulate, thereby favoring the acquisition of further genetic alterations and promoting tumorigenesis. Dysregulation of programmed cell death mechanisms plays an important role in the pathogenesis and progression of breast cancer, as well as in the responses of tumors to therapeutic intervention. Overexpression of anti-apoptotic members of the Bcl-2 family such as Bcl-2 and Bcl-XL has been implicated in cancer chemoresistance, whereas high levels of pro-apoptotic proteins such as Bax promote apoptosis and sensitize tumor cells to various anticancer therapies. Recently, a new member of the Bcl-2 family, BCL2L12, was cloned. The BCL2L12 gene is constitutively expressed in many tissues, suggesting that the encoded protein serves an important function in different cell types. In the present study, the expression of BCL2L12 gene was analyzed by reverse transcription-PCR (PT-PCR) in 70 breast cancer tissues. Our results indicate that BCL2L12 positive breast tumors are mainly of lower stage (I/II) or grade (I/II) (p=0.02 or p=0.04 respectively). Cox regression analysis revealed that BCL2L12 expression is positively related to disease-free (DFS) and overall survival (OS) at both univariate and multivariate analysis (p=0.021, p=0.029, p=0.032, p=0.044 respectively). Kaplan-Meier survival curves also demonstrated that patients with BCL2L12-positive tumors have significantly longer DFS and OS (p=0.002 and p<0.001 respectively). BCL2L12 expression may be regarded as a new independent favorable prognostic marker for breast cancer.Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

Factors Predictive of Distant Metastases in Patients With Breast Cancer Who Have a Pathologic Complete Response After Neoadjuvant Chemotherapy

2005 ◽  
Vol 23 (28) ◽  
pp. 7098-7104 ◽  
Author(s):  
Ana M. Gonzalez-Angulo ◽  
Sean E. McGuire ◽  
Thomas A. Buchholz ◽  
Susan L. Tucker ◽  
Henry M. Kuerer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Distant Metastases ◽  
Complete Response ◽  
Cox Regression Analysis

Purpose To identify clinicopathological factors predictive of distant metastasis in patients who had a pathologic complete response (pCR) after neoadjuvant chemotherapy (NC). Methods Retrospective review of 226 patients at our institution identified as having a pCR was performed. Clinical stage at diagnosis was I (2%), II (36%), IIIA (27%), IIIB (23%), and IIIC (12%). Eleven percent of all patients were inflammatory breast cancers (IBC). Ninety-five percent received anthracycline-based chemotherapy; 42% also received taxane-based therapy. The relationship of distant metastasis with clinicopathologic factors was evaluated, and Cox regression analysis was performed to identify independent predictors of development of distant metastasis. Results Median follow-up was 63 months. There were 31 distant metastases. Ten-year distant metastasis-free rate was 82%. Multivariate Cox regression analysis using combined stage revealed that clinical stages IIIB, IIIC, and IBC (hazard ratio [HR], 4.24; 95% CI, 1.96 to 9.18; P < .0001), identification of ≤ 10 lymph nodes (HR, 2.94; 95% CI, 1.40 to 6.15; P = .004), and premenopausal status (HR, 3.08; 95% CI, 1.25 to 7.59; P = .015) predicted for distant metastasis. Freedom from distant metastasis at 10 years was 97% for no factors, 88% for one factor, 77% for two factors, and 31% for three factors (P < .0001). Conclusion A small percentage of breast cancer patients with pCR experience recurrence. We identified factors that independently predicted for distant metastasis development. Our data suggest that premenopausal patients with advanced local disease and suboptimal axillary node evaluation may be candidates for clinical trials to determine whether more aggressive or investigational adjuvant therapy will be of benefit.

scholarly journals Prognostic value of metabolic activity of the psoas muscle evaluated by preoperative 18F-FDG PET-CT in breast cancer: a retrospective cross-sectional study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Keunyoung Kim ◽  
In-Joo Kim ◽  
Kyoungjune Pak ◽  
Taewoo Kang ◽  
Young Mi Seol ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metabolic Activity ◽  
Cox Regression ◽  
Surrogate Marker ◽  
Disease Free Survival ◽  
Psoas Muscle ◽  
Cox Regression Analysis ◽  
Standardized Uptake Values ◽  
The Mean ◽  
Receptor Negativity

Abstract Background This study aimed to evaluate the potential of metabolic activity of the psoas muscle measured by 18F-fluorodeoxyglucose positron emission tomography-computed tomography to predict treatment outcomes in patients with resectable breast cancer. Methods The medical records of 288 patients who had undergone surgical resection for stages I–III invasive ductal carcinoma of the breast between January 2014 and December 2014 in Pusan National University Hospital were reviewed. The standardized uptake values (SUVs) of the bilateral psoas muscle were normalized using the mean SUV of the liver. SUVRmax was calculated as the ratio of the maximum SUV of the average bilateral psoas muscle to the mean SUV of the liver. SUVRmean was calculated as the ratio of the mean SUV of the bilateral psoas muscle to the mean SUV of the liver. Results Univariate analyses identified a higher T stage, higher N stage, estrogen receptor negativity, progesterone receptor negativity, human epidermal growth factor receptor 2 positivity, triple-negative breast cancer, mastectomy (rather than breast-conserving surgery), SUVRmean > 0.464, and SUVRmax > 0.565 as significant adverse factors for disease-free survival (DFS). Multivariate Cox regression analysis revealed that N3 stage (hazard ratio [HR] = 5.347, P = 0.031) was an independent factor for recurrence. An SUVRmax > 0.565 (HR = 4.987, P = 0.050) seemed to have a correlation with shorter DFS. Conclusions A higher SUVRmax of the psoas muscle, which could be a surrogate marker of insulin resistance, showed strong potential as an independent prognostic factor for recurrence in patients with resectable breast cancer.

scholarly journals Identification of a prognostic long non-coding RNA signature in breast cancer

2020 ◽  
Author(s):  
Gaochen Lan ◽  
Xiaoling Yu ◽  
Yanna Zhao ◽  
Jinjian Lan ◽  
Wan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Cox Regression Analysis

Abstract Background: Breast cancer is the most common malignant disease among women. At present, more and more attention has been paid to long non-coding RNAs (lncRNAs) in the field of breast cancer research. We aimed to investigate the expression profiles of lncRNAs and construct a prognostic lncRNA for predicting the overall survival (OS) of breast cancer.Methods: The expression profiles of lncRNAs and clinical data with breast cancer were obtained from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were screened out by R package (limma). The survival probability was estimated by the Kaplan‑Meier Test. The Cox Regression Model was performed for univariate and multivariate analysis. The risk score (RS) was established on the basis of the lncRNAs’ expression level (exp) multiplied regression coefficient (β) from the multivariate cox regression analysis with the following formula: RS=exp a1 * β a1 + exp a2 * β a2 +……+ exp an * β an. Functional enrichment analysis was performed by Metascape.Results: A total of 3404 differentially expressed lncRNAs were identified. Among them, CYTOR, MIR4458HG and MAPT-AS1 were significantly associated with the survival of breast cancer. Finally, The RS could predict OS of breast cancer (RS=exp CYTOR * β CYTOR + exp MIR4458HG * β MIR4458HG + exp MAPT-AS1 * β MAPT-AS1). Moreover, it was confirmed that the three-lncRNA signature could be an independent prognostic biomarker for breast cancer (HR=3.040, P=0.000).Conclusions: This study established a three-lncRNA signature, which might be a novel prognostic biomarker for breast cancer.

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