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.

Purpose: We aimed to assess the real-world efficacy of nab-paclitaxel in metastatic breast cancer patients. Materials and Methods: This is a retrospective study performed in two tertiary referral hospitals in Korea. Patients with metastatic breast cancer treated with nab-paclitaxel (Abraxane®) between March 2016 and March 2020 were enrolled. Results: A total of 102 patients with metastatic breast cancer were included. Patients were heavily pre-treated with a median of four prior lines of chemotherapy (5 lines when including endocrine therapy in hormone-receptor-positive patients), and 66 patients (64.7%) were exposed to taxanes in the metastatic setting. According to St. Gallen molecular subtypes, 36 patients (35.3%) were luminal A, 28 (27.5%) were luminal B, 18 (17.7%) were human epidermal growth factor receptor 2–positive and 20 (19.6%) had triple-negative disease. Fifty patients (49.0%) were treated with a 3-weekly regimen (260 mg/m2 on day 1 every 3 weeks), and 52 (51.0%) were treated with a weekly regimen (100 mg/m2 every week). Objective response rate was 22.9%. After a median follow-up of 22.0 months, median progression-free survival (PFS) was 4.0 months (95% confidence interval [CI], 2.6 to 4.8) and median overall survival was 8.7 months (95% CI, 7.5 to 11.2). Patients treated with weekly regimen had longer PFS compared to 3-weekly regimen (5.5 vs. 2.3 months, p < 0.001). Multivariate analysis revealed the treatment regimen as an independent prognostic factor for PFS. There was no grade 3 or 4 hypersensitivity reaction. Conclusion This real-world data shows that nab-paclitaxel is a reasonable treatment option in heavily pre-treated and/or taxane-exposed metastatic breast cancer patients.

BACKGROUND: Ovarian epithelial cancer (OEC) is the second-most common gynecologic malignancy. CD109 expression is elevated in human tumor cell lines and carcinomas. A previous study showed that CD109 expression is elevated in human tumor cell lines and CD109 plays a role in cancer progression. Therefore, this study aimed to determine whether CD109 is expressed in OEC and can be useful in predicting the prognosis. METHODS: Immunohistochemical staining for CD109 and reverse transcription-quantitative polymerase chain reaction was performed. Then we compared CD109 expression and chemoresistance, overall survival, and recurrence-free survival of OEC patients. Chemoresistance was evaluated by dividing into good-response group and poor-response group by the time to recurrence after chemotherapy. RESULTS: CD109 expression was associated with overall survival (p = .020), but not recurrence-free survival (p = .290). CD109 expression was not an independent risk factor for overall survival due to its reliability (hazard ratio, 1.58; p = .160; 95% confidence interval, 0.82 to 3.05), although we found that CD109 positivity was related to chemoresistance. The poor-response group showed higher rates of CD109 expression than the good-response group (93.8% vs 66.7%, p = .047). Also, the CD109 mRNA expression level was 2.88 times higher in the poor-response group as compared to the good-response group (p = .001). CONCLUSIONS: Examining the CD109 expression in patients with OEC may be helpful in predicting survival and chemotherapeutic effect.
Cell Line, Tumor ; Drug Therapy ; Humans ; Polymerase Chain Reaction ; Prognosis ; Recurrence ; Risk Factors ; RNA, Messenger

PURPOSE: To report a case of recurrent endophthalmitis due to methicillin resistant Staphylococcus hemolyticus after phacoemulsification and posterior chamber intraocular lens (IOL) implantation. CASE SUMMARY: A 76-year-old female visited our outpatient clinic with decreased vision 40 days after uncomplicated cataract surgery in her right eye. At the visit, anterior chamber inflammation and cloudy fluid between the posterior capsule and IOL were observed. Uveitis due to residual cortex of lens or capsular block syndrome was suspected, so YAG laser capsulotomy and subconjunctival injection of dexamethasone were performed. Two days later, hypopyon and vitreous opacity were seen. The patient underwent an emergency vitrectomy and intravitreal antibiotic injection with suspicion of bacterial endophthalmitis. The culture was negative. Twenty days after the vitrectomy, anterior chamber inflammation and vitreous opacity developed. The recurrence of endophthalmitis was suspected due to infection by bacteria in the surrounding tissue of the IOL, so the patient underwent an IOL and lens capsule removal with intravitreal antibiotic injection. At this time, the culture revealed methicillin resistant staphylococcus hemolyticus. Systemic and topical vancomycin was then administered, resulting in decreased inflammation. Twenty days after the IOL removal, decreased vision, anterior chamber inflammation, and vitreous opacity developed. Endophthalmitis was decreased by intravitreal antibiotic injection and topical antibiotic treatment. CONCLUSIONS: Methicillin resistant staphylococcus hemolyticus should be considered in the differential diagnosis of chronic recurrent endophthalmitis after cataract surgery.
Aged ; Ambulatory Care Facilities ; Anterior Chamber ; Bacteria ; Cataract ; Dexamethasone ; Diagnosis, Differential ; Emergencies ; Endophthalmitis ; Female ; Humans ; Inflammation ; Lasers, Solid-State ; Lenses, Intraocular ; Methicillin Resistance ; Methicillin ; Phacoemulsification ; Recurrence ; Staphylococcus ; Uveitis ; Vancomycin ; Vitrectomy

BACKGROUND AND PURPOSE: The cerebrospinal fluid (CSF) biomarkers play an important supportive role as diagnostic and predictive indicators of Alzheimer's disease (AD). About 30% of controls in old age show abnormal values of CSF biomarkers and display a higher risk for AD compared with those showing normal values. The cut-off values are determined by their diagnostic accuracy. However, the current cut-off values may be less accurate, because controls include high-risk groups of AD. We sought to develop models of patients with AD, who are homogenous for CSF biomarkers. METHODS: We included participants who had CSF biomarker data in the Alzheimer's Disease Neuroimaging Initiative database. We investigated the factors related to CSF biomarkers in patients with AD using linear mixed models. Using the factors, we developed models corresponding to CSF biomarkers to classify patients with mild cognitive impairment (MCI) into high risk and low risk and analyzed the conversion from MCI to AD using the Cox proportional hazards model. RESULTS: APOE ε4 status and age were significantly related to CSF Aβ1-42. CSF t-tau, APOE ε2 status and sex were significant factors. The CSF p-tau181 was associated with age and frequency of diagnosis. Accordingly, we modeled the three CSF biomarkers of AD. In MCI without APOE ε4, our models were better predictors of conversion. CONCLUSIONS: We can interpret CSF biomarkers based on the models derived from the data obtained from patients with AD.
Alzheimer Disease* ; Apolipoproteins E ; Biomarkers ; Cerebrospinal Fluid ; Diagnosis ; Humans ; Methods* ; Mild Cognitive Impairment* ; Neuroimaging ; Proportional Hazards Models ; Reference Values

PURPOSE: The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been determined in breast cancers. Interferons can affect T-cell activity through direct and indirect mechanisms. Myxovirus resistance A (MxA) is an excellent marker of interferon activity. Here,we evaluated TILs and MxA expression in human epidermal growth factor receptor 2 (HER2)–positive breast cancers. MATERIALS AND METHODS: Ninety cases of hormone receptor (HR)+/HER2+ tumors and 78 cases of HR–/HER2+ tumors were included. The TILs level was assessed using hematoxylin and eosin–stained full face sections, and MxA expressionwas evaluated by immunohistochemistrywith a tissue microarray. RESULTS: MxA protein expression was significantly higher in tumors with high histologic grade (p=0.023) and high levels of TILs (p=0.002). High levels of TILs were correlated with high histological grade (p=0.001), negative lymphovascular invasion (p=0.007), negative lymph node metastasis (p=0.007), absence of HR expression (p < 0.001), abundant tertiary lymphoid structures (TLSs) around ductal carcinoma in situ (p=0.018), and abundant TLSs around the invasive component (p < 0.001). High levels of TILs were also associated with improved disease-free survival, particularly in HR–/HER2+ breast cancers. However, MxA was not a prognostic factor. CONCLUSION: High expression of MxA in tumor cells was associated with high levels of TILs in HER2-positive breast cancers. Additionally, a high level of TILs was a prognostic factor for breast cancer, whereas the level of MxA expression had no prognostic value.
Breast Neoplasms ; Breast* ; Carcinoma, Intraductal, Noninfiltrating ; Disease-Free Survival ; Epidermal Growth Factor* ; Hematoxylin ; Humans* ; Interferons ; Lymph Nodes ; Lymphocytes, Tumor-Infiltrating* ; Myxovirus Resistance Proteins ; Neoplasm Metastasis ; Orthomyxoviridae* ; Receptor, Epidermal Growth Factor* ; T-Lymphocytes

BACKGROUND: Skin laser treatment has improved significantly and has become an effective treatment approach for many skin diseases while also having applications for beauty treatments. However, since skin laser transfers energy directly to the skin, the misuse of such treatment may result in permanent damage to skin tissues. OBJECTIVE: This survey of Korean adults, conducted to obtain their perspectives on and their treatment experience with skin laser treatment, will be used to determine the current status of skin laser treatment and to identify necessary changes to ensure proper and safe conduct of skin laser treatment. METHODS: From April 5th to April 12th, 2016, a survey was conducted to obtain information regarding the perspectives and the treatment experience of adults aged 20~59 years. RESULTS: Approximately 50% of the participants had experience with skin laser treatment, and among these, 24.7% had not received treatment at a dermatology clinic. Compared to treatment at a dermatology clinic, the danger of side effects was 1.7 times higher at a non-dermatology clinic, 2 times higher at a skin care shop, and 5.3 times higher at an Oriental medical clinic. Among patients who received skin laser treatment, 16.1% experienced side effects, and among these, 1 out of 4 patients visited a non-dermatologist for treatment of these side effects. CONCLUSION: The results of the survey showed that in order for the public to receive safe and effective skin laser treatment based on professional diagnosis, there is a definitive need to provide correct information to the public and to implement changes to ensure proper understanding of skin laser treatment among this population.
Adult ; Beauty ; Dermatology ; Diagnosis ; Humans ; Skin Care ; Skin Diseases ; Skin*

BACKGROUND: Pyridoxal-5'-phosphate (P5P), a coenzyme of the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) reactions, is required to measure aminotransferase levels (IFCC method). However, a modified IFCC method that uses a reagent devoid of P5P is commonly used in laboratories in Korea. To determine the differences between the two methods, we compared aminotransferase levels measured by using the IFCC method and modified IFCC method. METHODS: Serum levels of AST and ALT, with and without P5P, were measured in 2,318 patients. Based on the allowable limits of performance set by the Royal College of Pathologists of Australasia (RCPA), differences between the two methods were analyzed under various conditions. RESULTS: Higher AST and ALT values were obtained by the IFCC method compared to modified IFCC method, showing significant differences between the two methods (AST, 5.8±14.2 IU/L; ALT, 2.8±6.9 IU/L) (P<0.001). Values exceeding RCPA criteria were more frequently observed in emergency orders (AST, 65.8%; ALT, 14.4%) than in routine orders (AST, 3.2%; ALT, 9.6%), as well as in inpatient wards (AST, 70.4%; ALT, 18.5%) compared to outpatient clinics (AST, 56.6%; ALT, 10.0%). However, the differences between the two methods were not significant among the disease groups, except for the acute myocardial infarction group. CONCLUSIONS: The method using reagents without P5P underestimated aminotransferase activity. The effect of P5P was more significant in patients with acute myocardial infarction, considered as P5P-deficient. In conclusion, the IFCC method with P5P should be applied for measuring AST and ALT serum levels.
Alanine Transaminase ; Ambulatory Care Facilities ; Aspartate Aminotransferases ; Australasia ; Emergencies ; Humans ; Indicators and Reagents ; Inpatients ; Korea ; Liver Function Tests ; Methods ; Myocardial Infarction ; Pyridoxal Phosphate