scholarly journals Comprehensive Association Analysis of 21-Gene Recurrence Score and Obesity in Chinese Breast Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Yiwei Tong ◽  
Weiqi Gao ◽  
Jiayi Wu ◽  
Siji Zhu ◽  
Ou Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Single Gene ◽  
Menopausal Status ◽  
Recurrence Score ◽  
Risk Category ◽  
Obese Patients ◽  
Breast Cancer Patients

PurposeA center-specific 21-gene recurrence score (RS) assay has been validated in Luminal-like, HER2-, pN0-1 Chinese breast cancer patients with both predictive and prognostic value. The association between RS and host factors such as obesity remains unclear. The objectives of the current study are to comprehensively analyze the distribution, single gene expression, and prognostic value of RS among non-overweight, overweight and obese patients.Patients and methodsLuminal-like patients between January 2009 and December 2018 were retrospectively reviewed. Association and subgroup analysis between BMI and RS were conducted. Single-gene expression in RS panel was compared according to BMI status. Disease-free survival (DFS) and overall survival (OS) were calculated according to risk category and BMI status.ResultsAmong 1876 patients included, 124 (6.6%), 896 (47.8%) and 856 (45.6%) had RS < 11, RS 11-25, and RS ≥ 26, respectively. Risk category was significantly differently distributed by BMI status (P=0.033). Obese patients were more likely to have RS < 11 (OR 2.45, 95% CI 1.38-4.35, P=0.002) compared with non-overweight patients. The effect of BMI on RS significantly varied according to menstruation (P<0.05). Compared to non-overweight patients, obese ones presented significantly higher ER, PR, CEGP1, Ki67, CCNB1 and GSTM1 (all P<0.05) mRNA expression, and such difference was mainly observed in postmenopausal population. After a median follow-up of 39.40 months (range 1.67-119.53), RS could significantly predict DFS in whole population (P=0.001). RS was associated with DFS in non-overweight (P=0.046), but not in overweight (P=0.558) or obese (P=0.114) population.ConclusionsRS was differently distributed among different BMI status, which interacted with menopausal status. Estrogen receptor and proliferation group genes were more expressed in obese patients, especially in postmenopausal population.

scholarly journals Oncotype DX Breast Cancer recurrence score resists inter-assay reproducibility with RT2-Profiler Multiplex RT-PCR

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Verena Schildgen ◽  
Mathias Warm ◽  
Michael Brockmann ◽  
Oliver Schildgen
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Single Gene ◽  
Cancer Recurrence ◽  
Recurrence Score ◽  
Oncotype Dx ◽  
Breast Cancer Patients ◽  
Predictive Values ◽  
Individual Gene

AbstractThe Oncotype Dx assay is frequently used to test if breast cancer patients can be spared from chemotherapy without negative effects for their future clinical course. However, due to conflicting data on the assay utility, in the recent past its reimbursement situation in Germany was revised; due to continued requests by clinicians for predictive values, our group decided to implement an Oncotype Dx like alternative assay with the objective of obtaining quality and cost optimization. Customized RT2-Profiler assays covering the 21 gene panel of the Oncotype Dx assay were applied to a pilot cohort of breast cancer patients with known Oncotype Dx Recurrence Score (RS). The Ct values obtained with RT2-Profiler-assays were used to calculate the unscaled Recurrence Score (RSu) values and the thereon based RS according to the Oncotype DX assay rules if available. Despite consistent assay performance it was impossible to establish correlations between RT2-Profiler recurrence scores with the respective Oncotype DX values not to mention exact matches. By following the Oncotype DX assay and its interpretation as close as possible we faced several obstructions such as lack of information on RNA amount used, missing units in the single gene expression report, missing references cited in the original study that should explain the determination of the recurrence score formula, and vague information on the normalization of the gene expression impeding the reproduction of Oncotype Dx results in other laboratories. Unfortunately, the Oncotype Dx assay cannot be confirmed by the customized RT2-profiler assay, not least because of the fact that the individual gene measurements are not provided in the medical report, although these are mandatory for the RS calculation. In fact, the “single gene report” only contains unscaled scores of the ER, PR, and Her2 genes without any internationally accepted unit used to describe a transcript quantity. Therefore a direct comparison with the in-house measurement to evaluate its performance is impossible. With regard to our findings and the fact that the Oncotype RS represents a likelihood of the risk of relapse it thus remains impossible to assess the clinical necessity of this assay.

Comprehensive Analysis of the Expression and Prognostic Significance of THBSs in Breast Cancer

2021 ◽  
Author(s):  
Jun Wang ◽  
Xuebing Zhan ◽  
Qian Luo ◽  
Yunshu Kuang ◽  
Xiao Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Protein Expression ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Expression Levels ◽  
Cancer Tissues ◽  
Mrna Expression Levels

Abstract Background: Breast cancer is one of the most common tumors for women worldwide. Thrombospondins (THBSs) are reported to play important roles in various cellular processes and are involved in the occurrence and development of human cancers. However, the expression and prognostic value of THBSs family in breast cancer remain unclear.Methods: In this study, we examined the genes and protein expression levels of THBSs and their prognostic value by synthesizing several mainstream databases, including Oncomine, Human Protein Atlas (HPA), UALCAN, and KM Plotter. We also analyzed THBS interaction networks, genetic alterations, functional enrichment, and drug sensitivity with several publicly accessible databases, including GEPIA, GeneMANIA, STRING, cBioPortal, Metascape and NCI-60 database.Results: The results showed that the mRNA expression levels of THBS1, THBS2, THBS3, and THBS5 in breast cancer tissues were significantly higher than in normal tissues. The mRNA expression levels of THBS4 were different in different subtypes of breast cancer, and the protein expression levels of THBS1, THBS2, and THBS4 in breast cancer tissues were higher than in normal breast tissues. Survival analysis showed that breast cancer patients with high THBS1 gene expression showed worse overall survival (OS), relapse-free survival (RFS), and post-progression survival (PPS), and breast cancer patients with high THBS2 gene expression also showed worse RFS. Conversely, lower THBS3 levels predicted worse RFS, and lower THBS4 levels predicted worse OS, RFS, and distant metastasis-free survival (DMFS). Conclusions: These results suggest that THBSs may be potential biomarkers for breast cancer.

scholarly journals Body Mass Index and Clinical Outcomes in Egyptian Women with Breast Cancer: A Multi-institutional Study

2020 ◽  
pp. 10-17
Author(s):  
Amrou Mamdouh Abdeen Shaaban ◽  
Ahmed Hassan Abd Aziz ◽  
Nada Sholkamy ◽  
Hoda Mokhtar ◽  
Shimaa Anwer Emam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Body Mass ◽  
Menopausal Status ◽  
Tumor Stage ◽  
Primary Objective ◽  
Obese Patients ◽  
Breast Cancer Patients

Purpose: The aim of this work was to evaluate the association between body mass index (BMI) and clinical outcomes among Egyptian female breast cancer patients. Methods: We reviewed the file registry of 629 patients with operable breast cancer regarding age, sex, height, weight, menopausal status, family history of breast cancer, tumor features, TNM arrangement and treatment during the period from January 2006 to December 2012. In our studies, obesity was defined as a BMI of ≥30 kg/m2. The primary objective was to estimate the effect of body mass index on the clinical outcomes of breast cancer patients including DFS and OAS. Results: A total of 629 patients with a mean age of 51.1 years. Stage III and Stage II presented 52% and 46.6% respectively. Overweight and obese patients represent 60.5% of all patient population. There was no association between tumor stage, grade or menopausal status and BMI. Patients with normal BMI showed a median survival of 95.3 months [CI: 54.6,136.06]. This was significantly higher than overweight and obese patients (p = 0.001). Nearly one-third of patients (29.1%) with normal BMI experienced disease relapse compared to 32.8% for overweight and obese patients, however, this was statistically not significant (0.097). Conclusion: According to the results of this retrospective study, increased BMI may be associated with less favorable prognosis of breast cancer patients.

scholarly journals Impact of Obesity on Clinicopathologic Characteristics and Disease Prognosis in Pre- and Postmenopausal Breast Cancer Patients: A Retrospective Institutional Study

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Nehad M. Ayoub ◽  
Rami J. Yaghan ◽  
Nour M. Abdo ◽  
Ismail I. Matalka ◽  
Laila M. Akhu-Zaheya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Molecular Subtypes ◽  
Menopausal Status ◽  
Cancer Recurrence ◽  
Age At Diagnosis ◽  
Prognostic Scores ◽  
Obese Patients ◽  
Breast Cancer Patients ◽  
Clinicopathologic Characteristics

Purpose. To investigate the association between obesity and breast cancer clinicopathologic characteristics at presentation along with prognostic impact among Jordanian breast cancer patients. Such data are lacking in Arabian countries. Methods. In this retrospective study, 348 breast cancer patients were included. Analyses were conducted for associations between body mass index (BMI) and age at diagnosis, tumor clinicopathologic characteristics, and molecular subtypes. Eight prognostic factors were considered, and total prognostic scores were calculated. The analysis was stratified by menopausal status. Multivariate logistic stepwise regression analysis was conducted to identify predictors for breast cancer recurrence and death. Results. Mean age at diagnosis was 50.98 ± 10.96 years. Mean BMI at diagnosis was 29.52 ± 5.32 kg/m2. Mean age at diagnosis was significantly higher for overweight and obese patients compared to underweight/normal patients (P<0.001). A significant positive correlation was observed between patient age and BMI at diagnosis (r = 0.251, P<0.001). Grade of carcinoma was significantly correlated with BMI in the whole population examined (P=0.003). Obese breast cancer patients had significantly higher prognostic scores compared to nonobese cases, indicating worse prognostic features at presentation (P=0.034). Stratification of data analysis based on menopausal status revealed significant associations between obesity and each of tumor stage and grade among postmenopausal but not premenopausal patients (P=0.019 and P=0.031, respectively). Similarly, postmenopausal obese patients had significantly higher prognostic scores compared to nonobese counterparts (P=0.007), indicating worse prognosis, a finding which was also absent among premenopausal breast cancer patients. No significant association between BMI with expression status of hormone receptors, HER2, lymphovascular invasion, and molecular subtypes was found among patients. BMI was a significant predictor for disease recurrence in which obese breast cancer patients had greater odds (2-fold) to develop locoregional and distant recurrence compared to nonobese cases (P=0.011). Conclusions. Obesity was associated with advanced stage and grade of breast carcinoma at diagnosis. The impact of BMI on clinicopathologic characteristics and prognosis was confined to postmenopausal cases. Jordanian obese breast cancer patients are at greater risk of breast cancer recurrence and reduced survival compared to their nonobese counterparts.

scholarly journals Incidence of febrile neutropenia with commonly used chemotherapy regimen in localized breast cancer

2020 ◽  
Vol 09 (01) ◽  
pp. 04-06 ◽  
Author(s):  
Nageswara Reddy Palukuri ◽  
Rajani Priya Yedla ◽  
Stalin Chowdary Bala ◽  
Siva Prasad Kuruva ◽  
Rachana Chennamaneni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Febrile Neutropenia ◽  
Cancer Patients ◽  
Chemotherapy Regimen ◽  
Performance Status ◽  
Menopausal Status ◽  
Significant Risk ◽  
Primary Prophylaxis ◽  
Risk Category ◽  
Breast Cancer Patients

Abstract Introduction: Breast cancer is the most frequently diagnosed cancer among the women. Most commonly used chemotherapy regimen is Doxorubicin and Cyclophosphamide (AC) which carries significant risk of febrile neutropenia. The aim of the study is to identify the incidence of febrile neutropenia and its effects on the delivery of chemotherapy in patients receiving following AC chemoregimen without primary prophylaxis. Materials and Methods: We retrospectively analyzed the case records of the localized breast cancer patients who were treated with AC chemoregimen without primary prophylaxis for febrile neutropenia. Results: Between 2013 and 2017, a total of 231 cases received AC chemoregimen. A total of 14 (6.1%) patients were found to have febrile neutropenia. All patients were recovered by day 19 and no deaths were observed. Except for ECOG performance status (P = 0.001) no significant association was found with age, co-morbidities, menopausal status, body surface area and stage of the cancer. There were no treatment delays or dose reductions because of febrile neutropenia. Conclusion: The incidence of FN with AC chemotherapy in breast cancer patients is relatively less in the present study. Routine primary prophylaxis is not recommended as this chemotherapy falls in to low risk category for FN but can be considered for patients with ECOG PS > 1. If the diagnosis of febrile neutropenia and institution of appropriate measures are prompt, FN did not affect the delivery of chemotherapy and thus compromise survival.

Gene expression profiles of circulating tumor cells in metastatic breast cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10504-10504
Author(s):  
Bianca Mostert ◽  
Anieta M Sieuwerts ◽  
Jaco Kraan ◽  
Joan Bolt-de Vries ◽  
Dieter Peeters ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Gene Profile

10504 Background: A circulating tumor cell (CTC) count is an established prognostic factor in metastatic breast cancer. Besides enumeration, CTC characterization promises to further improve outcome prediction and treatment guidance. We have previously shown the feasibility of measuring the expression of a panel of 96 clinically relevant genes in CTCs in a leukocyte background, and in the current study, we determined the prognostic value of CTC gene expression profiling in metastatic breast cancer. Methods: CTCs were isolated and enumerated from blood of 130 metastatic breast cancer patients prior to start of first-line systemic, endocrine or chemotherapeutic, therapy. Of these, 103 were evaluable for mRNA gene expression levels measured by quantitative RT-PCR in relation to time to treatment switch (TTS). Separate prognostic CTC gene profiles were generated by leave-one-out cross validation for all patients and for patients with ≥5 CTCs per 7.5 mL blood, and cut-offs were chosen to ensure optimal prediction of patients who might benefit from an early therapy switch. Results: In the total cohort, of whom 56% received chemotherapeutic and 44% endocrine therapy, baseline CTC count (≥5 versus <5 CTCs/7.5 mL blood) predicted for TTS (Hazard Ratio (HR) 2.92 [95% Confidence Interval (CI) 1.71 – 4.95] P <0.0001). A 16-gene CTC profile for all patients and a separate 9-gene CTC profile applicable for patients with ≥5 CTCs were identified, which distinguished those patients with TTS or death within 9 months from those with a more favorable outcome. Test performance for both profiles was favorable; the 16-gene profile had 90% sensitivity, 38% specificity, 50% positive predictive value (PPV) and 85% negative predictive value (NPV), and the 9-gene profile performed slightly better at 92% sensitivity, 52% specificity, 66% PPV and 87% NPV. In multivariate Cox regression analysis, the 16-gene profile was the only factor independently associated with TTS (HR 3.15 [95%CI 1.35 – 7.33] P 0.008). Conclusions: Two CTC gene expression profiles were discovered, which provide prognostic value in metastatic breast cancer patients. This study further underscores the potential of molecular characterization of CTCs.

Distribution and Short‐term Prognostic Value of the 21‐gene recurrence score in African American compared to White American breast cancer patients

2019 ◽  
Vol 25 (4) ◽  
pp. 667-671
Author(s):  
Ali Amro ◽  
Yalei Chen ◽  
Renee Barry ◽  
Laura Susick ◽  
Jessica Bensenhaver ◽  
...  
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Recurrence Score ◽  
Breast Cancer Patients ◽  
Short Term ◽  
White American

scholarly journals Intratumor Heterogeneity and Precision of Microarray-Based Predictors of Breast Cancer Biology and Clinical Outcome

2010 ◽  
Vol 28 (13) ◽  
pp. 2198-2206 ◽  
Author(s):  
William T. Barry ◽  
Dawn N. Kernagis ◽  
Holly K. Dressman ◽  
Ryan J. Griffis ◽  
J'Vonne D. Hunter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Cancer Biology ◽  
Single Gene ◽  
Intraclass Correlation ◽  
Intratumor Heterogeneity ◽  
Breast Cancer Patients ◽  
Clustering Methods

Purpose Identifying sources of variation in expression microarray data and the effect of variance in gene expression measurements on complex predictive and diagnostic models is essential when translating microarray-based experimental approaches into clinical assays. The technical reproducibility of microarray platforms is well established. Here, we investigate the additional impact of intratumor heterogeneity, a largely unstudied component of variance, on the performance of several microarray-based assays in breast cancer. Patients and Methods Genome-wide expression profiling was performed on 50 core needle biopsies from 18 breast cancer patients using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Global profiles of expression were characterized using unsupervised clustering methods and variance components models. Array-based measures of estrogen receptor (ER) and progesterone receptor (PR) status were compared with immunohistochemistry. The precision of genomic predictors of ER pathway status, recurrence risk, and sensitivity to chemotherapeutics was evaluated by interclass correlation. Results Global patterns of gene expression demonstrated that intratumor variation was substantially less than the total variation observed across the patient population. Nevertheless, a fraction of genes exhibited significant intratumor heterogeneity in expression. A high degree of reproducibility was observed in single-gene predictors of ER (intraclass correlation coefficient [ICC] = 0.94) and PR expression (ICC = 0.90), and in a multigene predictor of ER pathway activation (ICC = 0.98) with high concordance with immunohistochemistry. Substantial agreement was also observed for multigene signatures of cancer recurrence (ICC = 0.71) and chemotherapeutic sensitivity (ICC = 0.72 and 0.64). Conclusion Intratumor heterogeneity, although present at the level of individual gene expression, does not preclude precise microarray-based predictions of tumor behavior or clinical outcome in breast cancer patients.

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