Purpose: K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. Materials and Methods: Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). Results: In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. Conclusion The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Background: Single nucleotide polymorphisms (SNPs) are reportedly associated with repeated abortion. Thus, genetic analysis based on race is the key to developing accurate diagnostic tests. This study analyzed the genetic polymorphisms of recurrent pregnancy loss (RPL) patients among Korean women compared to the controls. Methods: In 53 women of RPL group and 50 controls, the genetic analysis was performed.The genotype distribution and allele frequency were analyzed statistically for the difference between the two groups. The association between each SNP marker and RPL risk was analyzed. Results: The genotypes of LEPR, endothelial nitric oxide synthase (eNOS), KDR, miR-27a, miR-449b, and tumor necrosis factor-alpha (TNF-α) were analyzed using odds ratio (OR) with 95% confidence intervals (CIs). Only the AG genotype of miR-449b (A>G) polymorphism showed significant association with the risk of RPL when compared to the AA genotype (OR, 2.39). The combination of GG/AG+GG/CA+AA genotypes for eNOS/ miR-449b/TNF-α was associated with 7.36-fold higher risk of RPL (OR, 7.36). The GG/ AG+GG combination for eNOS/miR-449b showed 2.43-fold higher risk for RPL (OR, 2.43). The combination of AG+GG/CA+AA genotypes for miR-449b/TNF-α showed a significant association with the risk of RPL (OR, 7.60). From the haplotype-based analysis, the G-G-A haplotype of eNOS/miR-449b/TNF-α and the G-A haplotype of miR-449b/TNF-α were associated with increased risk of RPL (OR, 19.31; OR, 22.08, respectively). Conclusion There is a significant association between the risk of RPL and miR-449b/TNF-αcombination, and therefore, genetic analysis for specific combined genotypes can be an important screening method for RPL in Korean women.

Purpose: Next-generation sequencing (NGS) can facilitate precision medicine approaches in metastatic colorectal cancer (mCRC) patients. We investigated the molecular profiling of Korean mCRC patients under the K-MASTER project which was initiated in June 2017 as a nationwide precision medicine oncology clinical trial platform which used NGS assay to screen actionable mutations. Materials and Methods: As of 22 January 2020, total of 994 mCRC patients were registered in K-MASTER project. Targeted sequencing was performed using three platforms which were composed of the K-MASTER cancer panel v1.1 and the SNUH FIRST Cancer Panel v3.01. If tumor tissue was not available, cell-free DNA was extracted and the targeted sequencing was performed by Axen Cancer Panel as a liquid biopsy. Results: In 994 mCRC patients, we found 1,564 clinically meaningful pathogenic variants which mutated in 71 genes. Anti-EGFR therapy candidates were 467 patients (47.0%) and BRAF V600E mutation (n=47, 4.7%), deficient mismatch repair/microsatellite instability–high (n=15, 1.5%), HER2 amplifications (n=10, 1.0%) could be incorporated with recently approved drugs. The patients with high tumor mutation burden (n=101, 12.7%) and DNA damaging response and repair defect pathway alteration (n=42, 4.2%) could be enrolled clinical trials with immune checkpoint inhibitors. There were more colorectal cancer molecular alterations such as PIK3CA, KRAS G12C, atypical BRAF, and HER2 mutations and even rarer but actionable genes that approved or ongoing clinical trials in other solid tumors. Conclusion K-MASTER project provides an intriguing background to investigate new clinical trials with biomarkers and give therapeutic opportunity for mCRC patients.

For patients at risk of premature ovarian failure with cancer treatment, it is an important option to re-implant the ovarian tissue (OT) after cryopreservation to preserve endocrine function and fertility. With this technique, about 30% of pregnancy success rate and about 90 live births have been reported to date. However, there has been no case report of successful in vitro fertilization (IVF) and embryo transfer (ET) with oocytes collected from transplanted cryopreserved OT in Korea. We report a 30-year old woman with rectal cancer who underwent IVF and ET after cryopreserved OT thawing and re-implantation. She has been diagnosed with stage IIIC rectal cancer after surgery, and right ovary was removed and cryopreserved between cycles of chemotherapy. After completion of chemotherapy and radiotherapy, the patient underwent orthotopic transplantation of cryopreserved OTs. Three months after transplantation, the serum follicle-stimulating hormone level decreased from 91.11 mIU/mL to 43.69 mIU/mL. Thereafter, the patient underwent 11 ovarian stimulation cycles, and in 7 cycles, follicle growth was observed at the OT graft site. In one of these cycles, the oocyte was successfully retrieved and one embryo was transplanted after IVF. The patient was not pregnant, but the cryopreservation of OT can save the fertility after anticancer chemotherapy.
Cryopreservation ; Drug Therapy ; Embryo Transfer* ; Embryonic Structures* ; Female ; Fertility ; Fertility Preservation ; Fertilization in Vitro* ; Follicle Stimulating Hormone ; Humans ; In Vitro Techniques* ; Korea ; Live Birth ; Oocytes ; Ovary ; Ovulation Induction ; Pregnancy ; Primary Ovarian Insufficiency ; Radiotherapy ; Rectal Neoplasms ; Transplantation ; Transplants

PURPOSE: The purpose of this study was to find factors affecting hospital nurses' cancer prevention health promoting behavior METHODS: The subjects were 308 nurses working in general hospitals with over 300 beds. Knowledge of cancer was assessed with 36 question items for six major cancers, and the attitude toward cancer was assessed with 10 items for cancer prevention and early detection. Cancer prevention health promotion behavior was assessed by 21 questions about diet, health life, and exercise. The collected data were analyzed using frequency and percentage, t-tests, one-way ANOVA, Pearson correlation coefficients, and stepwise multiple regression analysis. RESULTS: The score for knowledge of cancer was 25.12±3.33. The average score for attitude towards cancer was 30.41±4.08. The score of cancer prevention health promoting behaviors on cancer was 70.60±10.90. Cancer prevention health promoting behaviors were not correlated with cancer knowledge, and were positively correlated with cancer attitude (r=0.44, p < .001). There was a positive correlation with the cancer prevention attitude (r=0.49, p < .001) among the sub-areas of cancer attitude. CONCLUSION: The nurses' knowledge, attitude, and preventive health promotion behaviors of cancer were important for the health of individuals, patients and the general public, I think it is necessary to search for ways to actively promote cancer prevention health promoting behaviors in various directions and to confirm their effects.
Diet ; Health Promotion ; Hospitals, General* ; Humans

PURPOSE: The roles of circulating tumor cells (CTCs) as predictive and prognostic factors, as well as key mediators in the metastatic cascade, have been investigated. This study aimed to validate a method to quantify CTCs in peripheral blood using a real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay for cytokeratin (CK)-19 and to evaluate the utility of this assay in detecting CTCs in breast cancer patients. MATERIALS AND METHODS: Real-time monitoring PCR of fluorescently labeled specific hybridization probes for CK-19 mRNA was established. Peripheral blood samples from 30 healthy donors, 69 patients with early breast cancer, 47 patients with locally advanced breast cancer, and 126 patients with metastatic breast cancer were prospectively obtained and analyzed for CTC detection. RESULTS: CK-19 mRNA was not detectable in healthy subjects using the real-time RT-PCR method. The detection rates of CK-19 mRNA in breast cancer patients were 47.8% for early breast cancer (33/69), 46.8% for locally advanced breast cancer (22/47), and 61.1% for metastatic breast cancer (77/129). The detection rate of CK-19-positive CTCs in metastatic disease was slightly higher than early or locally advanced breast cancer; however, the detection rate according to disease burden was not statistically different (p=0.097). The detection rate was higher in patients with pleural metastasis (p=0.045). CTC detection was associated with poor survival (p=0.014). CONCLUSION: A highly specific and sensitive CK-19 mRNA-based method to detect CTCs in peripheral blood in breast cancer patients can be used in further prospective studies to evaluate the predictive and prognostic importance of CTCs.
Biomarkers, Tumor/*blood ; Breast Neoplasms/blood/*pathology ; Female ; Humans ; Keratin-19/*blood/genetics ; *Neoplastic Cells, Circulating ; Prognosis ; Prospective Studies ; RNA, Messenger/*blood ; Real-Time Polymerase Chain Reaction ; *Reverse Transcriptase Polymerase Chain Reaction/methods

PURPOSE: The purpose of this study is to investigate the prognostic value of lymph node (LN) ratio (LNR) in patients with breast cancer after neoadjuvant chemotherapy. MATERIALS AND METHODS: This retrospective analysis is based on the data of 814 patientswith stage II/III breast cancer treated with four cycles of doxorubicin/cyclophosphamide followed by four cycles of docetaxel before surgery. We evaluated the clinical significance of LNR (3 categories: low 0-0.20 vs. intermediate 0.21-0.65 vs. high 0.66-1.00) using a Cox proportional regression model. RESULTS: A total of 799 patients underwent breast surgery. Pathologic complete response (pCR, ypT0/isN0) was achieved in 129 patients (16.1%) (hormone receptor [HR] +/human epidermal growth factor receptor 2 [HER2] –, 34/373 [9.1%]; HER2+, 45/210 [21.4%]; triple negative breast cancer, 50/216 [23.1%]). The mean numbers of involved LN and retrieved LN were 2.70 (range, 0 to 42) and 13.98 (range, 1 to 64), respectively. The mean LNR was 0.17 (low, 574 [71.8%]; intermediate, 170 [21.3%]; high, 55 [6.9%]). In univariate analysis, LNR showed significant association with a worse relapse-free survival (3-year relapse-free survival rate 84.8% in low vs. 66.2% in intermediate vs. 54.3% in high; p < 0.001, log-rank test). In multivariate analysis, LNR did not show significant association with recurrence after adjusting for other clinical factors (age, histologic grade, subtype, ypT stage, ypN stage, lymphatic or vascular invasion, and pCR). In subgroup analysis, the LNR system had good prognostic value in HR+/HER2–subtype. CONCLUSION: LNR is not superior to ypN stage in predicting clinical outcome of breast cancer after neoadjuvant chemotherapy. However, the prognostic value of the LNR system in HR+/HER2–patients is notable and worthy of further investigation.
Breast Neoplasms* ; Breast* ; Cohort Studies* ; Drug Therapy* ; Humans ; Lymph Node Excision ; Lymph Nodes ; Multivariate Analysis ; Neoadjuvant Therapy ; Prognosis ; Receptor, Epidermal Growth Factor ; Recurrence ; Retrospective Studies* ; Survival Rate ; Triple Negative Breast Neoplasms

Brain metastasis affects one third of patients with HER2-positive breast cancer after treatment with trastuzumab. Surgical resection and radiation therapy are often unsuccessful at accomplishing complete control of metastasis. Lapatinib is presumed to cross the blood-brain barrier, and exhibits clinical activities for treatment of HER2-positive breast cancer. A 43-year-old woman was treated for early breast carcinoma with total mastectomy, axillary lymph-node dissection, and adjuvant chemotherapy with cyclophosphamide plus doxorubicin. After the end of adjuvant trastuzumab therapy, she was diagnosed with panhypopituitarism due to pituitary metastasis. Surgical removal and whole brain radiation therapy were performed, but a portion of viable tumor remained. Only taking lapatinib, the size of the metastatic lesion began to shrink. Trastuzumab may have controlled the micro-metastasis of breast cancer, but it was unable to control its progression to the central nervous system. Lapatinib is a possible option for HER2-positive metastatic breast cancer patients with brain metastasis.
Adult ; Blood-Brain Barrier ; Brain ; Breast Neoplasms* ; Breast* ; Central Nervous System ; Chemotherapy, Adjuvant ; Cyclophosphamide ; Doxorubicin ; Female ; Humans ; Hypopituitarism ; Mastectomy, Simple ; Neoplasm Metastasis*

We report on five cases of skin metastasis according to the breast cancer (BC) subtype. Two cases of HER2 positive BC showed only skin metastasis after immediate postoperative period and rapid clinical response to targeted therapy. Another two cases of triple negative BC showed thyroid and lung metastasis in addition to skin metastasis, and their response of cytotoxic chemotherapy was not definite. The other hormone positive BC showed skin metastasis only, with a longer, slower, less progressive pattern than other subtypes. Most cases of skin metastasis were detected at terminal stage of malignancy and were considered to have a limited survival period. However, some BC patients can survive longer if the targeted agents are effective. Therefore, physicians should provide detailed follow up of BC after curative treatment and understand the metastatic pattern of BC according to the subtype.
Breast Neoplasms* ; Drug Therapy ; Humans ; Lung ; Neoplasm Metastasis* ; Postoperative Period ; Skin Neoplasms ; Skin* ; Thyroid Gland

PURPOSE: The purpose of our study was to investigate the effects of hippotherapy on gross motor function and functional performance in children with spastic cerebral palsy (CP). MATERIALS AND METHODS: We recruited 34 children (M:F=15:19, age: 3-12 years) with spastic CP who underwent hippotherapy for 45 minutes twice a week for 8 weeks. Twenty-one children with spastic CP were recruited for control group. The distribution of gross motor function classification system level and mean age were not significantly different between the two groups. Outcome measures, including the Gross Motor Function Measure (GMFM)-66, GMFM-88 and the Pediatric Evaluation of Disability Inventory: Functional Skills Scale (PEDI-FSS), were assessed before therapy and after the 8-weeks intervention as outcome measures. RESULTS: There were no significant differences between intervention and control groups in mean baseline total scores of GMFM-66, GMFM-88 or PEDI-FSS. After the 8-weeks intervention, mean GMFM-66 and GMFM-88 scores were significantly improved in both groups. However, the hippotherapy group had significantly greater improvement in dimension E and GMFM-66 total score than the control group. The total PEDI-FSS score and the sub-scores of its 3 domains were significantly improved in the hippotherapy group, but not in the control group. CONCLUSION: The results of our study demonstrate the beneficial effects of hippotherapy on gross motor function and functional performance in children with CP compared to control group. The significant improvement in PEDI-FSS scores suggests that hippotherapy may be useful to maximize the functional performance of children with CP.
Activities of Daily Living ; Cerebral Palsy/physiopathology/*rehabilitation/*therapy ; Child ; Child, Preschool ; Disability Evaluation ; *Equine-Assisted Therapy ; Female ; Humans ; Male ; *Motor Skills ; Outcome and Process Assessment (Health Care) ; *Physical Therapy Modalities ; Recovery of Function