Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Cancer is a disease which has the huge burden in worldwide, and cancer is the number one cause of death in Korea. At this point, the new framework for cancer monitoring index is required for regional cancer monitoring. Especially, cancer survivors are the important target which is rapidly increasing recently, also cancer survivor’s quality of care should be considered in the cancer monitoring index framework. To develop the Multidimensional Cancer Monitoring Index considering cancer survivor’s quality of care, we took into account cancer continuum which including prevention, detection, diagnosis, treatment, survivorship, assessment of quality of care and monitoring cancer patient, and end-of life care for stage. For target, components of health care delivery system such as patient, family, provider, payer, and policy maker are included. Also, Donabedian model which is a framework for examining health services and evaluating quality of health care such as structure, process, and outcome is applied to contents. This new cancer monitoring framework which includes multidimensional components could help to develop regional cancer monitoring index, and to make national cancer management and prevention policy in the future.

OBJECTIVES: Albuminuria has emerged as a biomarker for several medical conditions, and vitamin D has received attention due to its associations with various disorders. We evaluated the association between low serum vitamin D levels and prevalent albuminuria by sex in the Korean general population. METHODS: We analyzed 9823 participants (4401 males, 5422 females) from the Korea National Health and Nutrition Examination Survey 2011-2012 (KNHANES V-2), and categorized them as having a normal range of vitamin D levels, vitamin D insufficiency, or vitamin D deficiency. A multivariable logistic regression model was used to compare the risk of albuminuria across these groups. Stratified analyses were conducted by smoking status, obesity, and renal function. RESULTS: Albuminuria was found in 325 of the 4401 male participants (7.4%) and in 455 of the 5422 female participants (8.4%). Among the males, vitamin D deficiency was associated with an odds ratio (OR) for albuminuria of 1.78 (95% confidence interval [CI], 1.07 to 2.97, p < 0.05). However, such an association was not found in females. The association was stronger in male current smokers (OR, 3.54; 95% CI, 1.47 to 8.50; p=0.005). CONCLUSIONS: The findings of this study suggest that sex differences exist in the association between serum vitamin D deficiency and albuminuria. Additionally, we observed that the association was stronger in current smokers than in the overall male population, but was not seen in non-smokers. Therefore, different approaches by sex and smoking status might be needed when considering using vitamin D as a biomarker for renal function.
Albuminuria* ; Cross-Sectional Studies* ; Female ; Humans ; Korea* ; Logistic Models ; Male ; Nutrition Surveys* ; Obesity ; Odds Ratio ; Reference Values ; Sex Characteristics ; Sex Factors ; Smoke ; Smoking ; Vitamin D Deficiency* ; Vitamin D* ; Vitamins*

BACKGROUND/AIMS: A number of genome-wide and candidate gene association studies have identified polymorphisms associated with telomere length in Caucasian populations. This study was conducted to determine the impacts of 17 polymorphisms identified in Caucasians on telomere length in a Korean population. METHODS: Ninety-four healthy individuals were enrolled in this study. Relative telomere length of chromosomes from peripheral blood samples was measured using quantitative polymerase chain reaction. RESULTS: Two polymorphisms, rs10936599 of MYNN and rs412658 of ZNF676, were found to be associated w ith telomere length (under dominant model, p = 0.04; under recessive model, p = 0.001). Three polymorphisms, rs2853669, rs7705526, and rs2736108, at the TERT locus were also associated with telomere length (under recessive model, p = 0.01, p = 0.02, and p = 0.01, respectively). The genotypes of the five polymorphisms associated with short telomere length were considered bad genotypes; telomere length was significantly decreased with increasing number of bad genotypes (p= 1.7 x 10(-5)). CONCLUSIONS: We have identified polymorphisms associated with telomere length in a Korean population.
Adult ; Aged ; Asian Continental Ancestry Group/*genetics ; Case-Control Studies ; DNA-Binding Proteins/genetics ; Female ; Genome-Wide Association Study ; Genotype ; Humans ; Kruppel-Like Transcription Factors/genetics ; Male ; Middle Aged ; Phenotype ; *Polymorphism, Single Nucleotide ; Republic of Korea ; Telomerase/genetics ; Telomere/*genetics/metabolism ; *Telomere Homeostasis ; Zinc Fingers

PURPOSE: This study examines the effects of a rehabilitation program on quality of life (QoL), cardiopulmonary function, and fatigue in breast cancer patients. The program included aerobic exercises as well as stretching and strengthening exercises. METHODS: Breast cancer patients (n=62) who had completed chemotherapy were randomly assigned to an early exercise group (EEG; n=32) or a delayed exercise group (DEG; n=30). The EEG underwent 4 weeks of a multimodal rehabilitation program for 80 min/day, 5 times/wk for 4 weeks. The DEG completed the same program during the next 4 weeks. The European Organization for Research and Treatment of Cancer-Core Quality of Life Questionnaire (EORTC QLQ-C30), EORTC Breast Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23), predicted maximal volume of oxygen consumption (VO2max), and fatigue severity scale (FSS) were used for assessment at baseline, and at 2, 4, 6, and 8 weeks. RESULTS: After 8 weeks, statistically significant differences were apparent in global health, physical, role, and emotional functions, and cancer-related symptoms such as fatigue and pain, nausea, and dyspnea on the EORTC QLQ-C30; cancer-related symptoms involving the arm and breast on the EORTC QLQ-BR23; the predicted VO2max; muscular strength; and FSS (p<0.050), according to time, between the two groups. CONCLUSION: The results of our study suggest that a supervised multimodal rehabilitation program may improve the physical symptoms, QoL, and fatigue in patients with breast cancer.
Arm ; Breast ; Breast Neoplasms* ; Drug Therapy ; Dyspnea ; Electroencephalography ; Exercise ; Fatigue* ; Humans ; Nausea ; Oxygen Consumption ; Quality of Life* ; Rehabilitation* ; Surveys and Questionnaires

Recently, rearranged during transfection (RET) fusions have been identified in approximately 1% of non-small cell lung cancer (NSCLC). To know the prevalence of RET fusion genes in Korean NSCLCs, we examined the RET fusion genes in 156 surgically resected NSCLCs using a reverse transcriptase polymerase chain reaction. Two KIF5B-RET fusions and one CCDC6-RET fusion were identified. All three patients were females and never smokers with adenocarcinomas. RET fusion genes were mutually exclusive from EGFR, KRAS mutations and EML4-ALK fusion. RET fusion genes occur 1.9% (3 of 156) of surgically treated NSCLC patients in Koreans.
Asian Continental Ancestry Group/*genetics ; Carcinoma, Non-Small-Cell Lung/epidemiology/*genetics/surgery ; Cytoskeletal Proteins/genetics ; Female ; Humans ; Kinesin/genetics ; Lung Neoplasms/epidemiology/*genetics/surgery ; Middle Aged ; Oncogene Proteins, Fusion/*genetics ; Proto-Oncogene Proteins c-ret/*genetics ; Republic of Korea/epidemiology ; Sequence Analysis, DNA

A genome-wide association study has identified the 15q25 region as being associated with the risk of chronic obstructive pulmonary disease (COPD) in Caucasians. This study intended as a confirmatory assessment of this association in a Korean population. The rs6495309C > T polymorphism in the promoter of nicotinic acetylcholine receptor alpha subunit 3 (CHRNA3) gene was investigated in a case-control study that consisted of 406 patients with COPD and 394 healthy control subjects. The rs6495309 CT or TT genotype was associated with a significantly decreased risk of COPD when compared to the rs6495309 CC genotype (adjusted odds ratio = 0.69, 95% confidence interval = 0.50-0.95, P = 0.023). The effect of the rs6495309C > T on the risk of COPD was more evident in moderate to very severe COPD than in mild COPD under a dominant model for the variant T allele (P = 0.024 for homogeneity). The CHRNA3 rs6495309C > T polymorphism on chromosome 15q25 is associated with the risk of COPD in a Korean population.
Adult ; Aged ; Alleles ; Asian Continental Ancestry Group/*genetics ; Case-Control Studies ; Female ; Forced Expiratory Volume ; Genotype ; Humans ; Male ; Middle Aged ; Odds Ratio ; *Polymorphism, Single Nucleotide ; Pulmonary Disease, Chronic Obstructive/*genetics/physiopathology ; Receptors, Nicotinic/*genetics ; Republic of Korea ; Risk Factors ; Smoking

A fusion gene between echinoderm microtubule-associated protein-like 4 (EML4) and the anaplastic lymphoma kinase (ALK) has been identified in non-small cell lung cancers (NSCLCs). Although a few studies have evaluated EML4-ALK fusion genes in Korean NSCLCs, the prevalence of different EML4-ALK fusion variants has yet to be clearly assessed. Herein, we have examined the profiles of EML4-ALK fusion gene variants in Korean patients of NSCLCs. EML4-ALK fusion genes have been detected in 10 (6.0%) of 167 patients of NSCLCs and in 9 (7.4%) of 121 patients of adenocarcinoma. Of the 10 patients with fusion genes identified, 8 (80%) were E13;A20 (variant 1) and 2 (20%) were E6;A20, with an additional 33-bp sequence derived from intron 6 of EML4 (variant 3b). These results indicate that the profiles of EML4-ALK fusion gene variants in Korean patients of NSCLC may differ from those in other ethnic populations. Herein, we describe for the first time the profiles of EML4-ALK fusion variants of Korean patients with NSCLCs.
Adenocarcinoma/diagnosis/genetics ; Aged ; Asian Continental Ancestry Group/*genetics ; Base Sequence ; Carcinoma, Non-Small-Cell Lung/diagnosis/*genetics ; Exons ; Female ; Humans ; Introns ; Lung Neoplasms/diagnosis/*genetics ; Male ; Middle Aged ; Oncogene Proteins, Fusion/chemistry/*genetics ; Republic of Korea ; Sequence Analysis, RNA ; Smoking