scholarly journals Prognostic Significance of Focal Adhesion Kinase in Node-Negative Breast Cancer

Breast Care ◽  
2017 ◽  
Vol 12 (5) ◽  
pp. 329-333 ◽  
Author(s):  
Katrin Almstedt ◽  
Isabel Sicking ◽  
Marco J. Battista ◽  
Shangou Huangfu ◽  
Anne-Sophie Heimes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Cox Regression ◽  
Prognostic Impact ◽  
Free Survival ◽  
Node Negative ◽  
Cox Regression Analysis ◽  
Luminal B ◽  
Prognostic Relevance

Background: Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays an important role as a mediator of cell migration, invasion, proliferation and survival. Conflicting results for the prognostic role of FAK in breast cancer (BC) prompted us to determine its impact. Methods: Patients with node-negative BC entered this retrospective study. FAK expression was determined by immunohistochemistry (n = 335). The prognostic impact of FAK was examined with Cox regression analyses and Kaplan-Meier estimation in the whole cohort as well as in different molecular subtypes. Results: 151 (45.1%) had a FAK-positive BC. In univariate analyses, FAK expression showed a significant impact for shorter disease-free survival (DFS) (hazard ratio (HR) 1.54, 95% confidence interval (CI) 1.04-2.28, p = 0.030) but not for metastasis-free survival and overall survival. Significant prognostic relevance for DFS (HR 1.76, 95% CI 1.05-2.97, p = 0.033) was observed in particular in estrogen receptor-positive HER2-negative BC patients, most notably in luminal B-like tumors (HR 2.32, CI 1.20-4.48, p = 0.012). However, FAK lost its prognostic impact in multivariate Cox regression analysis. Conclusion: FAK was associated with impaired DFS in univariate analysis. Prognostic relevance for DFS was most pronounced in luminal B-like BC. However, FAK expression was not associated with an independent impact on survival for BC in multivariate analysis.

Prognostic Impact of Cytogenetics and Early Response and Efficacy of Sequential High-Dose AraC and Idarubicin (S-HAI) in Patients with Refractory and Relapsed Acute Myeloid Leukemia (AML): Results of a Prospective Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 871-871
Author(s):  
Wolfgang Kern ◽  
Hubert Serve ◽  
Peter Staib ◽  
Christa Kerschgens ◽  
Anett Matylis ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Prospective Study ◽  
Cox Regression ◽  
High Dose ◽  
Prognostic Impact ◽  
Prognostic Parameters ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
A Prospective Study ◽  
Refractory Aml

Abstract Management of patients with refractory and relapsed AML needs optimization. We performed a prospective study in these patients aiming at 1) the definition of the anti-leukemic efficacy of the S-HAI regimen; and 2) the evaluation of the prognostic impact of cytogenetic aberrations at relapse in the context of other prognostic parameters. Treatment consisted of AraC 1 g/sqm q 12 h days 1, 2, 8, and 9 and idarubicin 10 mg/sqm days 3, 4, 10, and 11. AraC was given at 3 g/sqm in patients under age 60 with refractory AML or relapse after CR1 <6 months. Fludarabine was given according to randomization at 15 mg/sqm 4 h before each dose of AraC. Between May 1996 and February 2004 306 patients were randomized, 261 are fully evaluable. The patients′ characteristics were median age 55 years (range, 18-83); refractory AML/relapse with CR1<6 months/relapse with CR1 >6 months 13%/25%/62%; cytogenetics at relapse favorable/intermediate/unfavorable/not available 7%/44%/24%/25%; secondary AML 7%. Median duration of neutropenia <1000/μl was 37 days. Non-hematologic side effects III°/IV° included diarrhea (21%), mucositis (19%), nausea/vomiting (17%), hyperbilirubinemia (12%), and bleeding (8%). Encontered infections were pneumonia 51%, FUO 41%, bacteremia 28%, abdominal 23%, and catheter-related 16%. Response rates were CR 39%, partial remission 7%, persistent leukemia 36%, early death 18%. Median event-free survival (EFS) was 2.4 months, meidan relapse-free survival was 5.9 months, and median overall survival was 6.2 months. In 38% of patients a change of karyotype between diagnosis and relapse occurred. In general, cytogenetics (CG) at relapse had a higher prognostic impact as compared to CG at diagnosis and therefore was included in the following analyses of prognostic parameters. CR rate was significantly related to duration of CR1 (CR1 0 months 29%; CR1 <6 months 14%; CR1 >6<18 months 52%; CR1 >18 months 56%; p<0.0001) and CG at relapse (favorable CG 85%; intermediate CG 44%; unfavorable CG 21%; p<0.0001) but not to age < vs. >60 years (40% vs. 39%). EFS and OS were significantly related to duration of CR1 (p=0.0001 and p=0.0004) and CG at relapse (p=0.0002 and p=0.0009). Logistic regression analysis revealed CG at relapse (p=0.006) as well as duration of CR1 (p=0.004) being independently related to CR rate. Cox regression analysis revealed CG at relapse (p=0.001) and duration of CR1 (p=0.014) being independently related to EFS. CG at relapse was the only parameter independently related to OS (p=0.001). The inclusion of the therapy-dependent parameter, residual bone marrow blasts at day 18 (day 18 blasts), revealed day 18 blasts being independently related to CR rate, EFS, and OS. These data indicate that 1) the S-HAI regimen confers a significant anti-leukemic efficacy in patients with relapsed and refractory AML unless unfavorable CG are present; and 2) CG at relapse is the most important prognostic parameter in these patients and day 18 blasts may be used to early identify treatment failure and guide the decision about alternative treatment approaches.

scholarly journals Histopathological and Genomic Grading Provide Complementary Prognostic Information in Breast Cancer: A Study on Publicly Available Datasets

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Nilotpal Chowdhury
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Prognostic Indicator ◽  
Rank Test ◽  
Prognostic Impact ◽  
Prognostic Information ◽  
Free Survival ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Significant Prognostic Indicator

The genomic grade (GG) for breast cancer is thought to be the genomic counterpart of histopathological grade (HG). The motivation behind this study was to see whether HG retains its prognostic impact even when adjusted for GG, or whether it can be replaced by the latter. Four publicly available gene expression datasets were analyzed. Kaplan-Meier curves, log rank test, and Cox regression were used to study recurrence-free survival (RFS) and distant metastasis-free survival (DMFS). HG remained a significant prognostic indicator in low GG tumors (P = 0.003 for DMFS, P< 0.001 for RFS) but not in high GG tumors. HG grade 2 tumors differed significantly from HG grade 1 tumors, underlining the prognostic role of intermediate HG tumors. Additionally, GG could stratify HG 1 as well as HG 2 tumors into distinct prognostic groups. HG and GG add independent prognostic information to each other. However, the prognostic effects of both HG and GG are time varying, with the hazard ratios of high HG and GG tumors being markedly attenuated over time.

Ki-67 is a Luminal B marker that identifies a high-risk subgroup in hormone receptor positive and node negative breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10521-10521
Author(s):  
M. Cheang ◽  
D. Voduc ◽  
S. Leung ◽  
D. Turbin ◽  
P. S. Bernard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Breast Cancers ◽  
Ki 67 ◽  
Node Negative ◽  
Luminal B ◽  
Poor Outcome ◽  
Hormone Receptor Positive

10521 Background: Gene expression profiling studies have revealed prognostically significant intrinsic breast cancer subtypes, designated Luminal A, Luminal B, Basal and Her2. Expression of ER and associated genes characterizes the luminal breast cancers. The Lum B subgroup is associated with poor outcome, but we lack immunohistochemical (IHC) markers to distinguish Lum A and Lum B subgroups. MKI67 is one gene known to be highly expressed in Lum B tumors, encoding the Ki-67 protein, a robust marker of cell proliferation. In this study, we perform IHC analysis of Ki-67 in a large breast cancer tissue microarray. Methods: Our patient cohort consists of 2222 consecutive cases of invasive breast cancer referred to the BC Cancer Agency from 1986 to 1992. Archival paraffin tissue blocks were used to construct a tissue microarray that was then stained for Ki-67 using a commercially available mouse monoclonal antibody. Ki-67 staining was scored quantitatively by automated image analysis and a tumor was positive if the percent positive nuclei was >30%’ Results: Of the 2,222 patients, there are 1,437 Luminal tumors as defined by IHC (ER or PR positive). As Her2 positive status is an established marker of poor prognosis, we excluded these tumors from our analysis. Of the remaining tumors, 9% were Ki-67 positive when using a ki-67 cut off of 30% positive nuclei. In survival analysis of patients ER/PR positive and Her2 negative, we found that Ki-67 identifies a population with poor prognosis (10-yr BCSS 60% vs. 80%). In a multivariate Cox regression we found that Ki-67 is independently prognostic. We repeated Cox regression analysis including only node negative patients and again found that Ki-67 is an independent predictor of poor outcome. Conclusions: Ki-67 has prognostic significance on multivariate survival analysis. Hormone receptor positive and node negative status is typically associated with a favorable outcome for breast cancer. However, Ki-67 is able to identify a small, but clinically significant subgroup with a particularly poor outcome. Defining the Luminal B subtype as (ER or PR) positive and (HER2 or Ki-67) positive, results in a subgroup that contains 18% of hormone receptor positive breast cancers with 10-yr BCSS of 61%. No significant financial relationships to disclose.

Prognostic significance of Focal Adhesion Kinase (FAK) in node-negative breast cancer.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 552-552
Author(s):  
Marcus Schmidt ◽  
Leonie van de Sandt ◽  
Katrin Almstedt ◽  
Marco Johannes Battista ◽  
Anne-Sophie Heimes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Prognostic Significance ◽  
Node Negative ◽  
Node Negative Breast Cancer

Prognostic impact of LDH and HCG levels in marker-positive seminomas.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 392-392 ◽  
Author(s):  
Christoph Alexander Seidel ◽  
Gedske Daugaard ◽  
Tim Nestler ◽  
Alexey Tryakin ◽  
Christian Daniel Fankhauser ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Cox Regression ◽  
Serum Levels ◽  
Rank Test ◽  
Prognostic Impact ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Oncological Outcomes ◽  
Log Rank Test

392 Background: The prognostic impact of LDH and HCG serum levels in marker positive metastatic seminoma patients is uncertain. This analysis evaluated the association between LDH and HCG levels with oncological outcomes in this patient population. Methods: Seminoma patients with elevated HCG levels were retrospectively analyzed. After stratification according to tumor marker levels pre- and post-orchiectomy, outcomes of subgroups were compared using log-rank test and cox-regression analysis. Study endpoints were cancer specific- (CSS) and recurrence-free survival (RFS). Results: In total, 429 HCG-positive metastatic seminoma patients (stage II n=291; stage III n=138) diagnosed between 1981 and 2018 were included. LDH + HCG levels ranged from 124 U/l to 8833 U/l (median: 619; IQR: 955) + 2 IU/l to 283,782 IU/l (median: 20; IQR: 63) pre- and from 107 U/l to 8650 U/l (median: 324; IQR: 481) + 0 IU/l to 36700 IU/l post-orchiectomy (median: 30; IQR: 121), respectively. Five-year CSS and RFS rates were 90% and 79%, respectively. Patients with LDH levels pre-orchiectomy <1.5 UNL (n=142) had a 5-year CSS (RFS) rate of 97% (88%), compared to 86% (81%) for ≥1.5 to 3 UNL (n=40), 83% (77%) for >3 to 5 UNL (n=44) and 83% (72%) for >5 UNL (n=44) (CSS p <0.001; RFS p=0.142). Concerning LDH levels post-orchiectomy this stratification was not significant but patients with LDH levels ≥3 UNL (n=77) displayed an impaired prognosis associated with a 5-year CSS (RFS) rate of 85% (79%) compared to 94% (82%) for levels <3 UNL (n=186) (CSS p=0.025; RFS p=0.447). Patients with HCG levels ≥2000 IU/l (n=17) pre- but not post-orchiectomy had a 5-year CSS (RFS) rate of 73% (60%) compared to 94% (79%) for patients with HCG levels <2000 IU/l (n=855) (CSS p=0.09; RFS p=0.04). In cox-regression analysis LDH ≥1.5 UNL (p=0.037; HR 3.32, CI95%1.08-10.26) and HCG levels ≥2000 IU/l (p=0.044; HR 3.69, 95%CI1.04-13.13) pre-orchiectomy were confirmed as prognostic factors for CSS. Conclusions: LDH levels inversely correlate with survival outcomes, suggesting ≥1.5 UNL pre- and ≥3 UNL post-orchiectomy as potential cut-off values for further risk assessment. Patients with extensive HCG elevations may represent an unfavorable subgroup concerning RFS and CSS, but only few patients were affected.

Serum CA 15.3, CEA and ESR Patterns in Breast Cancer

1997 ◽  
Vol 12 (4) ◽  
pp. 168-173 ◽  
Author(s):  
M. Rubach ◽  
J.J. Szymendera ◽  
J. Kamińska ◽  
M. Kowalska
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Peak Level ◽  
Serum Markers ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Ca 15.3

Serum CA 15.3, CEA and ESR were longitudinally determined in 298 patients with breast cancer during postsurgical follow-up and/or therapy. Observation lasted until the death of the patient or at least for three years. With regard to longitudinal serum markers and ESR curves, four different patterns have been identified: pattern I: the markers and ESR stayed at normal levels; pattern II: the markers and ESR decreased from a peak level; pattern III: the markers and ESR fluctuated widely; pattern IV: the markers and ESR increased steadily. We have looked at overall survival (OS) and relapse-free survival (RFS) versus longitudinal CA 15.3, CEA and ESR patterns. Univariate Cox regression analysis showed that OS and RFS were significantly associated with all four patterns.

scholarly journals Significant Effect of Polymorphisms inCYP2D6andABCC2on Clinical Outcomes of Adjuvant Tamoxifen Therapy for Breast Cancer Patients

2010 ◽  
Vol 28 (8) ◽  
pp. 1287-1293 ◽  
Author(s):  
Kazuma Kiyotani ◽  
Taisei Mushiroda ◽  
Chiyo K. Imamura ◽  
Naoya Hosono ◽  
Tatsuhiko Tsunoda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Plasma Concentrations ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Tag Snps ◽  
Risk Alleles ◽  
Significant Difference ◽  
Variant Alleles

PurposeThe clinical efficacy of tamoxifen is suspected to be influenced by the activity of drug-metabolizing enzymes and transporters involved in the formation, metabolism, and elimination of its active forms. We investigated relationships of polymorphisms in transporter genes and CYP2D6 to clinical outcome of patients receiving tamoxifen.Patients and MethodsWe studied 282 patients with hormone receptor–positive, invasive breast cancer receiving tamoxifen monotherapy, including 67 patients who have been previously reported. We investigated the effects of allelic variants of CYP2D6 and haplotype-tagging single nucleotide polymorphisms (tag-SNPs) of ABCB1, ABCC2, and ABCG2 on recurrence-free survival using the Kaplan-Meier method and Cox regression analysis. Plasma concentrations of tamoxifen metabolites were measured in 98 patients receiving tamoxifen 20 mg/d.ResultsCYP2D6 variants were significantly associated with shorter recurrence-free survival (P = .000036; hazard ratio [HR] = 9.52; 95% CI, 2.79 to 32.45 in patients with two variant alleles v patients without variant alleles). Among 51 tag-SNPs in transporter genes, a significant association was found at rs3740065 in ABCC2 (P = .00017; HR = 10.64; 95% CI, 1.44 to 78.88 in patients with AA v GG genotypes). The number of risk alleles of CYP2D6 and ABCC2 showed cumulative effects on recurrence-free survival (P = .000000055). Patients carrying four risk alleles had 45.25-fold higher risk compared with patients with ≤ one risk allele. CYP2D6 variants were associated with lower plasma levels of endoxifen and 4-hydroxytamoxifen (P = .0000043 and .00052), whereas no significant difference was found among ABCC2 genotype groups.ConclusionOur results suggest that polymorphisms in CYP2D6 and ABCC2 are important predictors for the prognosis of patients with breast cancer treated with tamoxifen.

scholarly journals Impact of Multifocality on the Recurrence of Papillary Thyroid Carcinoma

2021 ◽  
Vol 10 (21) ◽  
pp. 5144
Author(s):  
Joohyun Woo ◽  
Hyeonkyeong Kim ◽  
Hyungju Kwon
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Cox Regression ◽  
Medical Center ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Papillary Thyroid ◽  
Free Survival ◽  
Cox Regression Analysis

The incidence of thyroid cancer has dramatically increased over the last few decades, and up to 60% of patients have multifocal tumors. However, the prognostic impact of multifocality in patients with papillary thyroid carcinoma (PTC) remains unestablished and controversial. We evaluate whether multifocality can predict the recurrence of PTC. A total of 1249 patients who underwent total thyroidectomy for PTC at the Ewha Medical Center between March 2012 and December 2019 were reviewed. In this study, multifocality was found in 487 patients (39.0%) and the mean follow-up period was 5.5 ± 2.7 years. Multifocality was associated with high-risk features for recurrence, including extrathyroidal extension, lymph node metastasis, and margin involvement. After adjustment of those clinicopathological features, 10-year disease-free survival was 93.3% in patients with multifocal tumors, whereas those with unifocal disease showed 97.6% (p = 0.011). Multivariate Cox regression analysis indicated that male sex (HR 2.185, 95% CI 1.047–4.559), tumor size (HR 1.806, 95% CI 1.337–2.441), N1b LN metastasis (HR 3.603, 95% CI 1.207–10.757), and multifocality (HR 1.986, 95% CI 1.015–3.888) were independent predictors of recurrence. In conclusion, multifocality increased the risk of recurrence in patients with PTC. Patients with multifocal PTCs may need judicious treatment and follow-up approaches.

scholarly journals Tumor microenvironmental prognosis analysis and molecular labeling of immune-related genes in Luminal B type breast cancer

2019 ◽  
Author(s):  
Fengjiao Gan ◽  
Kang Hu ◽  
Xiaomei Li ◽  
Ni Jiang ◽  
Qiaoyuan Wu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Cox Regression ◽  
Molecular Subtype ◽  
Clinical Results ◽  
Genomic Variation ◽  
Immune Gene ◽  
Cox Regression Analysis ◽  
Luminal B ◽  
The Relationship

Abstract Background: Tumor microenvironment (TME) cells is one of the important elements, constitute the tumor tissues and in predicting tumor clinical results and treatment effect has the important significance of clinical pathology. However, a detailed map for prognostic landscape of TME in Luminal B breast cancer is still lacking. Methods: ownloaded the expression profile and clinical follow-up information of luminal B breast cancer from TCGA and GEO, and used CIBERSORT to evaluate the infiltration mode of TME in 209 patients, and constructed the molecular subtype of luminal B breast cancer based on TME, further evaluated the relationship between molecular subtype and prognosis. DESeq2 was used to analyze the differentially expressed genes among molecular subtypes of luminal B breast cancer, and cox multivariate regression analysis was used for feature selection to construct TME signature. Results: ased on the median value of TMEscore, the samples were divided into High TMEscore and Low TMEscroe, and the relationship with prognosis, clinical features, immune gene expression and genomic variation was further evaluated. Different TME cells have significant correlation in luminal B breast cancer. These TME cells stratified different clinical results of luminal B breast cancer, and further TMEscore was established by Cox regression analysis. High TME score is associated with poor prognosis. Meanwhile, this study showed that CXCL10, CXCL9, GZMB and other immune activation genes and PDCD1LG2 and other immune checkpoint genes have higher expression levels in high TME score, and the mutation frequency of TP53 gene was lower in risk-H than that in risk-L. Conclusion: In this study, we systematically evaluated the TME infiltration patterns of 209 TCGA luminal B breast cancer patients and developed the TME score approach. It was found that TME score is a powerful prognostic biomarker and predictor of response to immunocheckpoint inhibitors and provides a new strategy for luminal B breast cancer immunotherapy.

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