Mutations affecting mRNA splicing define distinct clinical phenotypes and correlate with patient outcome in myelodysplastic syndromes

Abstract A cohort of MDS patients was examined for mutations affecting 4 splice genes (SF3B1, SRSF2, ZRSR2, and U2AF35) and evaluated in the context of clinical and molecular markers. Splice gene mutations were detected in 95 of 221 patients. These mutations were mutually exclusive and less likely to occur in patients with complex cytogenetics or TP53 mutations. SF3B1mut patients presented with lower hemoglobin levels, increased WBC and platelet counts, and were more likely to have DNMT3A mutations. SRSF2mut patients clustered in RAEB-1 and RAEB-2 subtypes and exhibited pronounced thrombocytopenias. ZRSR2mut patients clustered in International Prognostic Scoring System intermediate-1 and intermediate-2 risk groups, had higher percentages of bone marrow blasts, and more often displayed isolated neutropenias. SRSF2 and ZRSR2 mutations were more common in TET2mut patients. U2AF35mut patients had an increased prevalence of chromosome 20 deletions and ASXL1 mutations. Multivariate analysis revealed an inferior overall survival and a higher AML transformation rate for the genotype ZRSR2mut/TET2wt (overall survival: hazard ratio = 3.3; 95% CI, 1.4-7.7; P = .006; AML transformation: hazard ratio = 3.6; 95% CI, 2-4.2; P = .026). Our results demonstrate that splice gene mutations are among the most frequent molecular aberrations in myelodysplastic syndrome, define distinct clinical phenotypes, and show preferential associations with mutations targeting transcriptional regulation.

Download Full-text

Treatment Outcome of Patients with Myelodysplastic Syndromes (MDS) in Regular Care: Incidence of IPSS Risk Groups and Different Therapies in the German Outpatient MDS Registry

Blood ◽

10.1182/blood.v124.21.5601.5601 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5601-5601 ◽

Cited By ~ 1

Author(s):

H. Tilman Steinmetz ◽

Isolde Böttger ◽

Bernd Lathan ◽

Annette Sauer ◽

Enno Moorahrend ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Research Funding ◽

Risk Groups ◽

Outpatient Setting ◽

Observation Time ◽

Epigenetic Therapy ◽

International Prognostic Scoring System ◽

Course Of Disease ◽

Regular Care

Abstract The international prognostic scoring system (IPSS) for MDS patients (pts) receiving supportive care predicts a median overall survival of 68.4 months (mo), 42 mo, 14.4 mo and 4.8 mo according to the subgroups low, Int-1, Int-2, and high-risk, respectively. In July 2009, we established the German outpatient MDS registry with the aim to describe diagnostic procedures, treatment and course of disease of MDS pts in the community outpatient setting. In this analysis we evaluate the incidence of the IPSS subgroups, the frequencies of different therapies and the outcome, respectively. Methods: Newly diagnosed pts with MDS confirmed by bone marrow biopsy who gave informed consent were registered in an online database (IoStudy®). Baseline characteristics and diagnostics as well as a quarterly update of the course of disease were documented. Results: From July 2009 to March 2014 (56 mo) 1368 pts from 78 institutions were registered. Mean age was 73.5 years (y) (min-max 26.5 - 94.3 y, median 74.5 y) and 41% were women. 1,262 pts (92.3%) were evaluable for follow-up with a mean observation time (OT) of 21.7 mo (median: 19 mo). At diagnosis, IPSS risk classification was available in 898/1,262 (71%) pts. OT, overall survival (OS), number of pts (N) with epigenetic and iron-chelation therapy (ICT) over the entire term and the need of transfusions (tx) per quarter (Q) are given according to risk groups and treatment in the table. The figure shows the estimated Kaplan-Meyer-Plot for the IPSS risk groups. 180/1,315 pts (13.7%) received ICT, whereas 1,035 did not (86.3%). Median OS was 51 (95% confidential interval (CI) 44.7-57.3) and 49 mo (95% CI 43.7-54.3) (p = 0,281) for those with and without ICT, respectively. Conclusion: In the community outpatient setting in Germany, epigenetic therapy is used in a relative high proportion of pts with int-2 risk (57.1%) and high risk MDS (63.5%) at diagnosis, as well as in a substantial minority of patients with low-risk (6.7%) and int-1 risk (28.9%) MDS at progression. In the higher risk groups, transfusion need decreased more than 10% over time and overall survival was substantially longer than predicted by the IPSS. This may be considered as an empirical evidence for the efficacy of the new therapeutic options in regular care. Supported by Celgene, Munich, and Novartis, Erlangen, Germany Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Steinmetz: Novartis: Consultancy, Research Funding; Celgene: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Severin:Novartis: Research Funding; Celgene: Research Funding. Germing:Celgene: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau. Schmitz:Novartis: Consultancy, Research Funding; Celgene: Consultancy, Research Funding, Speakers Bureau. Gattermann:Celgene: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau.

Download Full-text

Evaluation of Ruxolitinib versus Best Available Therapy in Treating Primary Myelofibrosis

Sultan Qaboos University Medical Journal [SQUMJ] ◽

10.18295/squmj.8.2021.110 ◽

2021 ◽

Author(s):

Kawa M. Hasan ◽

Ahmed Y. Elmeshhadany ◽

Nazar P. Shabila

Keyword(s):

Overall Survival ◽

Kinase Inhibitor ◽

Laboratory Data ◽

Primary Myelofibrosis ◽

Risk Groups ◽

Janus Kinase ◽

Response To Treatment ◽

International Prognostic Scoring System ◽

Janus Kinase Inhibitor ◽

Treatment Groups

Objectives: Ruxolitinib is a Janus kinase inhibitor (JAK) that is approved for the treatment of myelofibrosis. The therapeutic protocol has changed after the introduction of Ruxolitinib. The aim of this study was to evaluate the effectiveness of Ruxolitinib and to compare it with best available therapy in patients with primary myelofibrosis. Methods: In this retrospective study, 72 patients with primary myelofibrosis were scrutinized in the period from 2012 to 2018 at Nanakali hemato-oncology teaching center, Erbil, Iraqi Kurdistan. The patients were divided into 2 cohorts, 26 of them were treated with Ruxolitinib and 46 others received best available therapy. The patients’ characteristics, their response to treatment, and the outcomes were evaluated. The efficacy of treatment in both arms was compared. Results: The majority our studied patients (46, 63.8%) were in the high and intermediate-2 risk groups according to international prognostic scoring system. At time of diagnosis, there were no noticeable differences in the clinical characteristics and laboratory data among the Ruxolitinib and best available treatment groups of patients. Ruxolitinib was found to be effective in reducing the size of spleen and improving the overall survival when compared to best available treatment group (p<0.001, p= 0.008 respectively). The patients’ performance state had a significant effect on the overall survival in both treatment groups (p=0.003). Conclusion: Ruxolitinib has a significant role in reduction of spleen size, and potentially affect the survival outcomes in patients with myelofibrosis. Keywords: Ruxolitinib, Myelofibrosis, Splenomegaly, Outcomes.

Download Full-text

Contribution of Inherited DNA-Repair Gene Mutations to Hormone-Sensitive and Castrate-Resistant Metastatic Prostate Cancer and Implications for Clinical Outcome

JCO Precision Oncology ◽

10.1200/po.19.00067 ◽

2019 ◽

pp. 1-12

Author(s):

Siddhartha Yadav ◽

Steven N. Hart ◽

Chunling Hu ◽

David Hillman ◽

Kun Y. Lee ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Metastatic Prostate Cancer ◽

Gene Mutations ◽

Germline Mutations ◽

Hazard Ratio ◽

Poor Overall Survival ◽

Mutation Status ◽

Hormone Sensitive ◽

Castrate Resistant

PURPOSE To compare the prevalence of germline mutations in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castrate-resistant prostate cancer (mCRPC) and assess the impact of mutations on progression to castration resistance and overall survival. METHODS Targeted sequencing of germline DNA from 704 men (221 at the time of mHSPC and 483 at the time of mCRPC) enrolled in two advanced prostate cancer registries at Mayo Clinic between 2003 and 2013 was performed for 21 predisposition genes. Frequencies of pathogenic mutations were compared in patients and reference controls to identify genes enriched in metastatic prostate cancer. Multivariable Cox proportional hazards regression was used to identify predictors of progression to mCRPC and overall survival. RESULTS Sixty-eight germline mutations in 12 genes were identified in 66 men (9.4%). Mutations in ATM, BRCA2, CHEK2, FANCM, and TP53 were significantly enriched (odds ratio greater than 2.0) in the metastatic cohorts compared with reference controls. The frequency of germline mutations was similar for patients with mHSPC and mCRPC (11.8% v 8.3%; P = .16). The median time to progression from mHSPC to mCRPC was 23.1 and 32.5 months for patients with and without mutations, respectively ( P = .96). Although older age at diagnosis, Gleason score greater than 7, elevated alkaline phosphatase level, and high volume of disease were associated with shorter duration of progression to mCRPC and poor overall survival, mutation status was not (progression to mCRPC hazard ratio, 0.81; 95% CI, 0.61 to 1.09; P = .17; overall survival hazard ratio, 1.00; 95% CI, 0.75 to 1.34; P = .98). CONCLUSION Similarly elevated rates of germline predisposition gene mutations in mHSPC and mCRPC suggest that germline genetic testing may help to guide medical management for all patients with advanced metastatic prostate cancer. Mutation status was not associated with shorter progression to mCRPC or poor overall survival.

Download Full-text

Development and validation of an individualized immune prognostic model in stage I–III lung squamous cell carcinoma

Scientific Reports ◽

10.1038/s41598-021-92115-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Qi-Fan Yang ◽

Di Wu ◽

Jian Wang ◽

Li Ba ◽

Chen Tian ◽

...

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Prognostic Model ◽

Lung Squamous Cell Carcinoma ◽

Risk Groups ◽

Stage I ◽

Tissue Samples ◽

Mutation Burden

AbstractLung squamous cell carcinoma (LUSC) possesses a poor prognosis even for stages I–III resected patients. Reliable prognostic biomarkers that can stratify and predict clinical outcomes for stage I–III resected LUSC patients are urgently needed. Based on gene expression of LUSC tissue samples from five public datasets, consisting of 687 cases, we developed an immune-related prognostic model (IPM) according to immune genes from ImmPort database. Then, we comprehensively analyzed the immune microenvironment and mutation burden that are significantly associated with this model. According to the IPM, patients were stratified into high- and low-risk groups with markedly distinct survival benefits. We found that patients with high immune risk possessed a higher proportion of immunosuppressive cells such as macrophages M0, and presented higher expression of CD47, CD73, SIRPA, and TIM-3. Moreover, When further stratified based on the tumor mutation burden (TMB) and risk score, patients with high TMB and low immune risk had a remarkable prolonged overall survival compared to patients with low TMB and high immune risk. Finally, a nomogram combing the IPM with clinical factors was established to provide a more precise evaluation of prognosis. The proposed immune relevant model is a promising biomarker for predicting overall survival in stage I–III LUSC. Thus, it may shed light on identifying patient subset at high risk of adverse prognosis from an immunological perspective.

Download Full-text

The development and validation of prognostic models for overall survival in the presence of missing data in the training dataset: a strategy with a detailed example

Diagnostic and Prognostic Research ◽

10.1186/s41512-021-00103-9 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Kara-Louise Royle ◽

David A. Cairns

Keyword(s):

Overall Survival ◽

Missing Data ◽

Prognostic Model ◽

Prognostic Index ◽

Risk Groups ◽

Prognostic Models ◽

Training Dataset ◽

Validation Process ◽

Test Dataset ◽

Development And Validation

Abstract Background The United Kingdom Myeloma Research Alliance (UK-MRA) Myeloma Risk Profile is a prognostic model for overall survival. It was trained and tested on clinical trial data, aiming to improve the stratification of transplant ineligible (TNE) patients with newly diagnosed multiple myeloma. Missing data is a common problem which affects the development and validation of prognostic models, where decisions on how to address missingness have implications on the choice of methodology. Methods Model building The training and test datasets were the TNE pathways from two large randomised multicentre, phase III clinical trials. Potential prognostic factors were identified by expert opinion. Missing data in the training dataset was imputed using multiple imputation by chained equations. Univariate analysis fitted Cox proportional hazards models in each imputed dataset with the estimates combined by Rubin’s rules. Multivariable analysis applied penalised Cox regression models, with a fixed penalty term across the imputed datasets. The estimates from each imputed dataset and bootstrap standard errors were combined by Rubin’s rules to define the prognostic model. Model assessment Calibration was assessed by visualising the observed and predicted probabilities across the imputed datasets. Discrimination was assessed by combining the prognostic separation D-statistic from each imputed dataset by Rubin’s rules. Model validation The D-statistic was applied in a bootstrap internal validation process in the training dataset and an external validation process in the test dataset, where acceptable performance was pre-specified. Development of risk groups Risk groups were defined using the tertiles of the combined prognostic index, obtained by combining the prognostic index from each imputed dataset by Rubin’s rules. Results The training dataset included 1852 patients, 1268 (68.47%) with complete case data. Ten imputed datasets were generated. Five hundred twenty patients were included in the test dataset. The D-statistic for the prognostic model was 0.840 (95% CI 0.716–0.964) in the training dataset and 0.654 (95% CI 0.497–0.811) in the test dataset and the corrected D-Statistic was 0.801. Conclusion The decision to impute missing covariate data in the training dataset influenced the methods implemented to train and test the model. To extend current literature and aid future researchers, we have presented a detailed example of one approach. Whilst our example is not without limitations, a benefit is that all of the patient information available in the training dataset was utilised to develop the model. Trial registration Both trials were registered; Myeloma IX-ISRCTN68454111, registered 21 September 2000. Myeloma XI-ISRCTN49407852, registered 24 June 2009.

Download Full-text

A prognostic model based on seven immune-related genes predicts the overall survival of patients with hepatocellular carcinoma

BioData Mining ◽

10.1186/s13040-021-00261-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Qian Yan ◽

Wenjiang Zheng ◽

Boqing Wang ◽

Baoqian Ye ◽

Huiyan Luo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

High Risk ◽

Risk Score ◽

Immune Cells ◽

Prognostic Model ◽

Risk Groups ◽

Low Risk ◽

Prognostic Performance ◽

Immune Related Genes

Abstract Background Hepatocellular carcinoma (HCC) is a disease with a high incidence and a poor prognosis. Growing amounts of evidence have shown that the immune system plays a critical role in the biological processes of HCC such as progression, recurrence, and metastasis, and some have discussed using it as a weapon against a variety of cancers. However, the impact of immune-related genes (IRGs) on the prognosis of HCC remains unclear. Methods Based on The Cancer Gene Atlas (TCGA) and Immunology Database and Analysis Portal (ImmPort) datasets, we integrated the ribonucleic acid (RNA) sequencing profiles of 424 HCC patients with IRGs to calculate immune-related differentially expressed genes (DEGs). Survival analysis was used to establish a prognostic model of survival- and immune-related DEGs. Based on genomic and clinicopathological data, we constructed a nomogram to predict the prognosis of HCC patients. Gene set enrichment analysis further clarified the signalling pathways of the high-risk and low-risk groups constructed based on the IRGs in HCC. Next, we evaluated the correlation between the risk score and the infiltration of immune cells, and finally, we validated the prognostic performance of this model in the GSE14520 dataset. Results A total of 100 immune-related DEGs were significantly associated with the clinical outcomes of patients with HCC. We performed univariate and multivariate least absolute shrinkage and selection operator (Lasso) regression analyses on these genes to construct a prognostic model of seven IRGs (Fatty Acid Binding Protein 6 (FABP6), Microtubule-Associated Protein Tau (MAPT), Baculoviral IAP Repeat Containing 5 (BIRC5), Plexin-A1 (PLXNA1), Secreted Phosphoprotein 1 (SPP1), Stanniocalcin 2 (STC2) and Chondroitin Sulfate Proteoglycan 5 (CSPG5)), which showed better prognostic performance than the tumour/node/metastasis (TNM) staging system. Moreover, we constructed a regulatory network related to transcription factors (TFs) that further unravelled the regulatory mechanisms of these genes. According to the median value of the risk score, the entire TCGA cohort was divided into high-risk and low-risk groups, and the low-risk group had a better overall survival (OS) rate. To predict the OS rate of HCC, we established a gene- and clinical factor-related nomogram. The receiver operating characteristic (ROC) curve, concordance index (C-index) and calibration curve showed that this model had moderate accuracy. The correlation analysis between the risk score and the infiltration of six common types of immune cells showed that the model could reflect the state of the immune microenvironment in HCC tumours. Conclusion Our IRG prognostic model was shown to have value in the monitoring, treatment, and prognostic assessment of HCC patients and could be used as a survival prediction tool in the near future.

Download Full-text

Mortality due to cancer treatment delay: systematic review and meta-analysis

BMJ ◽

10.1136/bmj.m4087 ◽

2020 ◽

pp. m4087 ◽

Cited By ~ 5

Author(s):

Timothy P Hanna ◽

Will D King ◽

Stephane Thibodeau ◽

Matthew Jalink ◽

Gregory A Paulin ◽

...

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Confidence Interval ◽

Cancer Treatment ◽

Head And Neck ◽

Adjuvant Radiotherapy ◽

Systemic Treatment ◽

Meta Analysis ◽

Treatment Delay ◽

Hazard Ratio

Abstract Objective To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways. Design Systematic review and meta-analysis. Data sources Published studies in Medline from 1 January 2000 to 10 April 2020. Eligibility criteria for selecting studies Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models. Results The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings. Conclusions Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.

Download Full-text

Abstract P319: Association of Heart Rate Reserve with Incidence of Hypertension in Men

Circulation ◽

10.1161/circ.127.suppl_12.ap319 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Vivek K Prasad ◽

Gregory A Hand ◽

Mei Sui ◽

Duck C Lee ◽

Deepika Shrestha ◽

...

Keyword(s):

Heart Rate ◽

Exercise Test ◽

Heavy Drinking ◽

Risk Groups ◽

Hazard Ratio ◽

Maximal Heart Rate ◽

Heart Rate Reserve ◽

Incident Hypertension ◽

The Difference ◽

Design And Methods

Abstract Objectives— We examined the association between heart rate reserve (HRR) and incident hypertension in men in the Aerobics Center Longitudinal Study. Research design and Methods— A total of 10418 healthy normotensive men, who did not have an abnormal electrocardiogram or a history of heart attack, stroke, cancer, or diabetes, performed a maximal treadmill exercise test and were followed for the incidence of hypertension. HRR was defined as the difference between maximal heart rate during exercise test and resting heart rate. Results— During a mean follow-up of 6 years, there were 2831 cases of incident hypertension. Compared with men in the reference category (the lowest quartile of HRR), the risk of incident hypertension was significantly lower in the highest quartile of HRR with a hazard ratio 0.67 (95% CI: 0.60-0.75) when adjusted for age and baseline examination year. Further adjustment for smoking, heavy drinking, body mass index (BMI), resting systolic and diastolic blood pressure, cholesterol, blood glucose and cardio respiratory fitness, resulted a hazard ratio of 0.84 (95% CI:0.74-0.95). This result was almost similar when we stratified them into younger and older men with hazard ratio of 0.77(95% CI: 0.62-0.98) and 0.78 (95% CI: 0.66-0.90) respectively. We also found a significant lower hypertension risk associated with higher HRR among high risk groups such as overweight, low fitness, or prehypertension with hazard ratio of 0.82(95% CI:0.70-0.97), 0.80(95% CI:0.67-0.96), 0.76(95% CI:0.64-0.88) respectively. Conclusion— Risk of Incident hypertension was significantly lower in men with higher HRR. High HRR was also associated with lower risk of developing hypertension irrespective of age and status of risk factors such as high BMI, low fitness and prehypertension. Therefore, HRR may be considered as a reliable exercise parameter for predicting the risk of incident hypertension.

Download Full-text

Comparative Efficacy and Safety of Adjuvant Letrozole Versus Anastrozole in Postmenopausal Patients With Hormone Receptor–Positive, Node-Positive Early Breast Cancer: Final Results of the Randomized Phase III Femara Versus Anastrozole Clinical Evaluation (FACE) Trial

Journal of Clinical Oncology ◽

10.1200/jco.2016.69.2871 ◽

2017 ◽

Vol 35 (10) ◽

pp. 1041-1048 ◽

Cited By ~ 34

Author(s):

Ian Smith ◽

Denise Yardley ◽

Howard A. Burris ◽

Richard De Boer ◽

Dino Amadori ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Adverse Events ◽

Early Breast Cancer ◽

Clinical Evaluation ◽

Hormone Receptor ◽

Hazard Ratio ◽

Efficacy And Safety ◽

Node Positive ◽

To Receive

Purpose The Letrozole (Femara) Versus Anastrozole Clinical Evaluation (FACE) study compared the efficacy and safety of adjuvant letrozole versus anastrozole in postmenopausal patients with hormone receptor (HR) –positive and node-positive early breast cancer (eBC). Methods Postmenopausal women with HR-positive and node-positive eBC were randomly assigned to receive adjuvant therapy with either letrozole (2.5 mg) or anastrozole (1 mg) once per day for 5 years or until recurrence of disease. Patients were stratified on the basis of the number of lymph nodes and human epidermal growth factor receptor 2 status. The primary end point was 5-year disease-free survival (DFS), and the key secondary end points were overall survival and safety. Results A total of 4,136 patients were randomly assigned to receive either letrozole (n = 2,061) or anastrozole (n = 2,075). The final analysis was done at 709 DFS events (letrozole, 341 [16.5%]; anastrozole, 368 [17.7%]). The 5-year estimated DFS rate was 84.9% for letrozole versus 82.9% for anastrozole arm (hazard ratio, 0.93; 95% CI, 0.80 to 1.07; P = .3150). Exploratory analysis showed similar DFS with letrozole and anastrozole in all evaluated subgroups. The 5-year estimated overall survival rate was 89.9% for letrozole versus 89.2% for anastrozole arm (hazard ratio, 0.98; 95% CI, 0.82 to 1.17; P = .7916). Most common grade 3 to 4 adverse events (> 5% of patients) reported for letrozole versus anastrozole were arthralgia (3.9% v 3.3%, and 48.2% v 47.9% for all adverse events), hypertension (1.2% v 1.0%), hot flushes (0.8% v 0.4%), myalgia (0.8% v 0.7%), dyspnea (0.8% v 0.5%), and depression (0.8% v 0.6%). Conclusion Letrozole did not demonstrate significantly superior efficacy or safety compared with anastrozole in postmenopausal patients with HR-positive, node-positive eBC.

Download Full-text