The Risk Factors, Incidence and Prognosis of Postpartum Breast Cancer: A Nationwide Study by the SMARTSHIP Group.

The term 'pregnancy-associated breast cancer' is no longer used as it has been consistently reported that breast cancer during pregnancy and breast cancer after delivery (postpartum breast cancer) have different characteristics and prognosis. The purpose of this study is to define postpartum breast cancer by analyzing the incidence rate, related factors, and prognosis according to the timing of breast cancer. Data from the Korean National Health Insurance Service were used to analyze 1,292,727 women aged 20-49 years who birthed their first child between 2007 and 2012. The annual incidence rate of breast cancer after delivery increased every year (7.7 per 10,000 person-years after 5 years, 19.36 per 10,000 person-years after 10 years). The risk of breast cancer was significantly higher (hazard ratio 1.15, 95% CI 1.05-1.27, P=0.0037) in women diagnosed with gestational diabetes, but that was not associated with overall survival (OS). Patients diagnosed with breast cancer within 5 years of delivery had a poorer prognosis than those diagnosed later (5-year OS, <5 years: 91.1% vs. 5-10 years: 96.0%). In multivariate analysis of OS, the hazard ratio of patients diagnosed within 5 years after delivery was twice as high as of patients diagnosed between 5 and 10 years. Women diagnosed with gestational diabetes had an increased risk of breast cancer. Breast cancer patients diagnosed within 5 years of delivery had a poorer prognosis than those diagnosed later. In this regard, careful screening for early diagnosis of high-risk patients and intensive research on new treatment strategies are needed.

Prognostic Factors in Male Breast Cancer: A Retrospective Nationwide Study in South Korea by the Study of SMARTSHIP Group.

This study evaluated the incidence, the survival outcomes and its prognostic factors for male breast cancer (MBC) in Korea. Using the National Health Insurance Service database of Korea, we identified MBC patients who had the new claim code of C50. Medical records including type of surgeries and radiotherapy within one year of the first claim and death records were reviewed. Between 2005 and 2016, 838 newly diagnosed MBC patients were included (median follow-up, 1,769 days). The 70-74-year age group had the highest incidence of MBC. The 5-year survival rate was 73.7%. Age > 65 years, low income, no surgical intervention, no tamoxifen use, and > 2 comorbidities correlated with a worse outcome. MBC incidence has increased over time, and its peak is noted at age > 70 years. Age > 65 years, > 2 comorbidities, no surgical intervention, and no tamoxifen use correlate to poor prognosis.

Comparison between video-lighted stylet (Intular Scope™) and direct laryngoscope for endotracheal intubation in patients with normal airway.

OBJECTIVE: The Intular Scope™ (Medical Park, South Korea) (IS) is a video-lighted stylet that can be used for endotracheal intubation with excellent visualization by adding a camera to its end. We compared the efficacy of a direct laryngoscope (DL) with that of the IS based on hemodynamic changes, ease of intubation, and postoperative airway morbidities. METHODS: Seventy patients with expected normal airways were randomized for intubation using an IS (n = 35) or DL (n = 35). The primary outcome was the mean arterial pressure during intubation. The secondary outcomes were the time to intubation (TTI), percentage of glottic opening (POGO) score, and number of intubation attempts. The incidence and severity of bleeding, hoarseness, and sore throat after intubation were also recorded. RESULTS: Hemodynamic changes during intubation were not significantly different between the groups. The TTI was longer in the IS than DL group. The POGO score was higher in the IS than DL group. Hoarseness and sore throat were significantly less severe in the IS than DL group. CONCLUSIONS: Using the IS did not significantly improve hemodynamics and resulted in a longer TTI. However, the IS was associated with less severe postoperative airway morbidities compared with the DL.

Localized primary breast amyloidosis and 1-year changes in imaging: A case report.

Localized primary breast amyloidosis is a very rare benign disease characterized by abnormal protein deposition in the mammary glands. Amyloidosis may mimic the appearance of a number of pathologies, both benign and malignant. Clinically, the patient may present with a breast mass or simply with increased breast density and skin thickening. Herein, we report the case of a 45-year-old woman who presented with a breast mass and was ultimately diagnosed with primary breast amyloidosis, and the mass diagnosed with amyloidosis increased in size and there were a greater number of amorphous and irregular microcalcifications on mammography and ultrasound at the 1-year follow-up. To conclude, we presented changes in a case of localized primary breast amyloidosis on mammography and ultrasound images over a period of 1 year. The current standard of care of primary breast amyloidosis is surgical resection; however, the patient should be followed after surgery to monitor the possibility of recurrence of malignancy.

Influence of Metabolic Syndrome on Risk of Breast Cancer: A Study Analyzing Nationwide Data from Korean National Health Insurance Service.

BACKGROUND: To investigate the influence of metabolic syndrome and its components on the risk of breast cancer. METHODS: Retrospective nationwide cohort study analyzing data of 13,377,349 women older than 19 years from Korean National Health Insurance Service was performed. Cox proportional hazards model was used to calculate HR and 95% confidence interval (CI) of breast cancer risk. RESULTS: The presence of metabolic syndrome decreased the risk of all breast cancer types in all subjects (HR, 0.954; 95% CI, 0.939-0.970). In women with age ≤50 years, metabolic syndrome decreased the risk of all breast cancer types, with similar findings for all subject groups (HR, 0.915; 95% CI, 0.892-0.939). In women with age >50 years, metabolic syndrome increased the risk of all breast cancer types (HR, 1.146; 95% CI, 1.123-1.170), especially in age groups of more than 55 years. In women with age >50 years, HRs increased as the number of metabolic syndrome components increased, while HRs decreased as the number of metabolic syndrome components increased in women with age ≤50 years. CONCLUSIONS: The presence of metabolic syndrome increased the risk of breast cancers in postmenopausal women, but decreased the risk in premenopausal women. Every metabolic syndrome component played similar roles on the risk of breast cancer as metabolic syndrome, and their effects became stronger when the number of components increased. IMPACT: Metabolic syndrome is associated with the risk of breast cancer having different effect according to age groups.

Long-term risk of congestive heart failure in younger breast cancer survivors: A nationwide study by the SMARTSHIP group.

BACKGROUND: There is a controversy about late-onset congestive heart failure (CHF) among breast cancer survivors. This study investigated the incidence rate and risk factors of late-onset CHF more than 2 years after the breast cancer diagnosis. METHODS: A nationwide, retrospective study was conducted with the National Health Information Database. With 1:3 age- and sex-matched noncancer controls, Cox proportional hazard regression models were used to analyze the incidence and risk factors of late CHF. The cumulative incidence rate of late CHF was evaluated with a Kaplan-Meier analysis and a log-rank test. RESULTS: A total of 91,227 cases (286,480 person-years) and 273,681 controls (884,349 person-years) were evaluated between January 2007 and December 2013. The risks of late CHF were higher in cases than controls (hazard ratio [HR], 1.396; 95% confidence interval [CI], 1.268-1.538). Younger survivors (age ≤ 50 years) showed a higher risk of late CHF than their younger counterparts (HR, 2.903; 95% CI, 2.425-3.474). Although older age was a risk factor for late CHF, older survivors (age ≥ 66 years) showed no difference in the risk of late CHF in comparison with their counterparts (HR, 0.906; 95% CI, 0.757-1.084). Anthracyclines and taxanes were risk factors for late CHF, although trastuzumab, radiation, and endocrine therapy were not. CONCLUSIONS: Young breast cancer survivors have a greater risk of late CHF than the young population without cancer. More attention should be paid to young breast cancer survivors who receive taxane- or anthracycline-based regimens over the long term.

Prevalence of breast cancer-related risk factors in underweight premenopausal women: the Korea National Health and Nutrition Examination Survey IV-VI.

PURPOSE: This study aimed to examine the prevalence and trends of breast cancer-related risk factors and characteristics in premenopausal underweight Korean women according to birth year cohort. METHODS: Socioeconomic and breast cancer-related risk factors were investigated in 13,415 premenopausal women using nationwide cross-sectional surveys performed between 2007 and 2015. Underweight was defined as body mass index < 18.5 kg/m2. Multivariable models were created using complex sample procedures. RESULTS: Underweight women comprised 9.5% of the sample. Compared with those who were obese or of normal weight, underweight women were characterized by younger age, higher rate of metropolitan residence, higher economic status, more education, higher rates of non-manual employment and unmarried status, lower rate of early menarche, higher rates of nulliparity, lower parity, alcohol consumption, and never having breastfed, and lower levels of high physical activity. Multivariable analysis showed that underweight women had a significantly lower rate of early menarche, lower parity, higher nulliparity, older age at first delivery, and lower levels of high physical activity compared to premenopausal women with normal weight. These trends were more apparent among women born in recent years. CONCLUSIONS: Underweight Korean premenopausal women exhibit distinctive features associated with an increased risk of breast cancer, except for a lower rate of early menarche. These associations were prominent in recent generations. Assessment of the association between underweight and premenopausal breast cancer risk should focus on promoting healthy lifestyles to reduce breast cancer risk.

Nationwide Analysis of Treatment Patterns for Korean Breast Cancer Survivors Using National Health Insurance Service Data.

BACKGROUND: The National Health Insurance Service (NHIS) established a healthcare claim database for all Korean citizens. This study aimed to analyze the NHIS data and investigate the patterns of breast cancer treatments. METHODS: We constructed a retrospective female breast cancer cohort by analyzing annual incident cases. The annual number of newly diagnosed female breast cancer was compared between the NHIS data and Korea National Cancer Incidence Database (KNCIDB). The annual treatment patterns including surgery, chemotherapy, radiation therapy, endocrine therapy and targeted therapy were analyzed. RESULTS: A total of 148,322 women with newly diagnosed invasive breast cancer during 2006-2014 was identified. The numbers of newly diagnosed invasive breast cancer cases were similar between the NHIS data and KNCIDB, which demonstrated a strong correlation (r = 0.995; P < 0.001). The age distribution of the breast cancer cases in the NHIS data and KNCIDB also showed a strong correlation (r = 1.000; P < 0.001). About 85% of newly diagnosed breast cancer patients underwent operations. Although the proportions of chemotherapy use have not changed during 2006-2014, the total number of chemotherapy prescriptions sharply increased during this period. The proportions of radiotherapy and anti-hormonal therapy increased. Among the anti-hormonal agents, tamoxifen was the most frequently prescribed medication, and letrozole was the most preferred endocrine treatment in patients aged ≥ 50 years. CONCLUSION: Along with the increased breast cancer incidence in Korea, the frequencies of breast cancer treatments have increased. The NHIS data can be a feasible data source for future research.

Prevalence and risk factors of latent tuberculosis among Korean healthcare workers using whole-blood interferon-γ release assay.

Because healthcare workers (HCWs) are at high risk for tuberculosis (TB) infection, it is essential to research the prevalence of latent TB infection (LTBI) and to implement health interventions including early treatment of LTBI and TB infection control measures. The purpose of the study was to determine the prevalence and risk factors for LTBI using interferon-γ release assay (IGRA) among HCWs in South Korea. The cross-sectional study was carried in the National Health Insurance Service Ilsan Hospital, which is a 740-bed general hospital, South Korea. HCWs who participated in this survey were required to complete a questionnaire and IGRA was performed. Of the 1,655 HCWs, 271 results were positive and the prevalence of LTBI was 16% (95% CI; 15-18%). In the multivariate analysis, age (OR; 2.201, 95% CI; 1.911-2.536, P < 0.001), male sex (OR; 1.523, 95% CI; 1.133-2.046, P = 0.005), contact active TB patients (OR; 1.461, 95% CI; 1.061-2.010, P = 0.02) and diabetes (OR; 2.837, 95% CI; 1.001-8.044, P = 0.05) were significant risk factors for LTBI. LTBI among HCWs in Korea, although prevalent, might not exceed the background level of the general population. Because contact with active TB patients has been identified as a risk factor for LTBI, more effective TB infection control measures are essential in healthcare facilities and congregate settings.

Up-regulation of HOXB cluster genes are epigenetically regulated in tamoxifen-resistant MCF7 breast cancer cells.

Tamoxifen (TAM) is commonly used to treat estrogen receptor (ER)-positive breast cancer. Despite the remarkable benefits, resistance to TAM presents a serious therapeutic challenge. Since several HOX transcription factors have been proposed as strong candidates in the development of resistance to TAM therapy in breast cancer, we generated an in vitro model of acquired TAM resistance using ER-positive MCF7 breast cancer cells (MCF7-TAMR), and analyzed the expression pattern and epigenetic states of HOX genes. HOXB cluster genes were uniquely up-regulated in MCF7-TAMR cells. Survival analysis of in slico data showed the correlation of high expression of HOXB genes with poor response to TAM in ER-positive breast cancer patients treated with TAM. Gain- and loss-of-function experiments showed that the overexpression of multi HOXB genes in MCF7 renders cancer cells more resistant to TAM, whereas the knockdown restores TAM sensitivity. Furthermore, activation of HOXB genes in MCF7-TAMR was associated with histone modifications, particularly the gain of H3K9ac. These findings imply that the activation of HOXB genes mediate the development of TAM resistance, and represent a target for development of new strategies to prevent or reverse TAM resistance. [BMB Reports 2018; 51(9): 450-455].

A Personalized and Learning Approach for Identifying Drugs with Adverse Events.

PURPOSE: Adverse drug events (ADEs) are associated with high health and financial costs and have increased as more elderly patients treated with multiple medications emerge in an aging society. It has thus become challenging for physicians to identify drugs causing adverse events. This study proposes a novel approach that can improve clinical decision making with recommendations on ADE causative drugs based on patient information, drug information, and previous ADE cases. MATERIALS AND METHODS: We introduce a personalized and learning approach for detecting drugs with a specific adverse event, where recommendations tailored to each patient are generated using data mining techniques. Recommendations could be improved by learning the associations of patients and ADEs as more ADE cases are accumulated through iterations. After consulting the system-generated recommendations, a physician can alter prescriptions accordingly and report feedback, enabling the system to evolve with actual causal relationships. RESULTS: A prototype system is developed using ADE cases reported over 1.5 years and recommendations obtained from decision tree analysis are validated by physicians. Two representative cases demonstrate that the personalized recommendations could contribute to more prompt and accurate responses to ADEs. CONCLUSION: The current system where the information of individual drugs exists but is not organized in such a way that facilitates the extraction of relevant information together can be complemented with the proposed approach to enhance the treatment of patients with ADEs. Our illustrative results show the promise of the proposed system and further studies are expected to validate its performance with quantitative measures.

Effect of Mild Hypercapnia on Lung Oxygenation in Sitting Position During Shoulder Arthroscopy Under General Anesthesia.

BACKGROUND Mild hypercapnia is permitted during surgeries in sitting position under general anesthesia to maintain cerebral regional oxygen saturation (rSO2). However, since hypoventilation may cause gas exchange impairment, we evaluated effects of mild hypercapnia on lung oxygenation during shoulder arthroscopy in sitting position. MATERIAL AND METHODS Forty patients were randomly allocated to a normocapnia group (ETCO2 35 mmHg, n=20) or a hypercapnia group (45 mmHg, n=20). The mean arterial pressure (MAP), heart rate (HR), and rSO2 were measured 5 min after intubation in supine position (T0), and at 2, 4, 6, 8, 10, 20, 30, 40, 50, and 60 min of remaining in sitting position (T1-10). Arterial blood gas was analyzed at T0 and T5. The oxygenation index (PaO2/FiO2) and dead-space ventilation ratio (Vd/Vt) were calculated. RESULTS There were no differences in PaO2/FiO2 at T0 and T5 between the 2 groups. At T5, the Vd/Vt was higher in the normocapnia group than in the hypercapnia group (p=0.04). The Vd/Vt at T5 increased from T0 in the normocapnia group. The incidence of cerebral desaturation in the hypercapnia group (0/20) was lower than in the normocapnia group (5/20) (p=0.047). Among rSO2, MAP, and HR, only changes in rSO2 over time between the 2 groups differed significantly (p=0.048). CONCLUSIONS Mild hypercapnia did not decrease lung oxygenation in sitting position, probably due to attenuation of the increase in dead-space ventilation ratio. Since hypercapnia maintained rSO2 without changes in oxygenation index and hemodynamic parameters, mild hypercapnia should be maintained during shoulder arthroscopy in sitting position under general anesthesia.

The mitotic checkpoint regulator RAE1 induces aggressive breast cancer cell phenotypes by mediating epithelial-mesenchymal transition.

The gene RAE1 encodes ribonucleic acid export 1 (RAE1), which is involved in mRNA export and is known to serve as a mitotic checkpoint regulator. In addition, RAE1 haplo-insufficiency leads to chromosome missegregation and early aging-associated phenotypes. In humans, a positive correlation has been found between RAE1 copy number abnormalities and gene amplification in breast cancer cells. However, the precise functional role of RAE1 in breast cancer remains to be determined. An in silico analysis of data retrieved from GENT and cBio-Portal identified RAE1 upregulation in breast cancer tissues relative to normal breast cells. Functional studies of various cell lines showed that RAE1 induced invasive and migratory abilities by regulating epithelial-mesenchymal transition signals. A tissue microarray was constructed to demonstrate the interrelationship between clinicopathological features and RAE1 expression. Immunohistochemistry revealed a positive correlation between RAE1 expression and a high histologic grade. Furthermore, RAE1 overexpression was associated with considerably poorer disease-free survival and distant metastasis-free survival, especially in patients with oestrogen receptor-positive tumours. In summary, RAE1 may be a prognostic marker and therapeutic intervention target in malignant breast cancers.

HOXC9 Induces Phenotypic Switching between Proliferation and Invasion in Breast Cancer Cells.

HOX genes encode a family of transcriptional regulators that are involved in pattern formation and organogenesis during embryo development. In addition, these genes play important roles in adult tissues and some of the dysregulated HOX genes are associated with cancer development and metastasis. Like many other HOX genes, HOXC9 is aberrantly expressed in certain breast cancer cell lines and tissues; however, its specific functions in breast cancer progression were not investigated. In the present study, we demonstrated that HOXC9 overexpression in breast cancer cell lines such as MDA-MB-231 and MCF7 increased the invasiveness but reduced the proliferation of cells, resembling a phenotype switch from a proliferative to an invasive state. Furthermore, the reciprocal result was detected in MCF7 and BT474 cells when the expression level of HOXC9 was reduced with siRNA. The clinical impact of HOXC9 in breast cancer was interpreted from the survival analysis data, in which high HOXC9 expression led to considerably poorer disease-free survival and distant metastasis-free survival, especially in lymph node-positive patients. Together, the prognostic relevance of HOXC9 and the HOXC9-derived phenotypic switch between proliferative and invasive states in the breast cancer cell lines suggest that HOXC9 could be a prognostic marker in breast cancer patients with lymph node metastasis and a target for therapeutic intervention in malignant breast cancer.

HOXB5 Promotes the Proliferation and Invasion of Breast Cancer Cells.

HOX transcription factors play an important role in determining body patterning and cell fate during embryogenesis. Accumulating evidence has shown that these genes act as positive and/or negative modulators in many types of cancer, including breast cancer, in a tissue-specific manner. We have previously reported that HOXB5 is aberrantly overexpressed in breast cancer tissues and cell lines. Here, we investigated the biological roles and clinical relevance of HOXB5 in breast cancer. Immunohistochemical analysis of HOXB5 on tissue microarray (TMA) including 34 normal and 67 breast cancer specimens revealed that HOXB5 was highly expressed in cancer tissues, particularly from estrogen receptor (ER)-positive breast cancer patients. An online survival analysis confirmed the correlation between HOXB5 expression and poor distant metastasis-free survival in ER-positive, but not in ER-negative, breast cancer. In vitro studies indicated that HOXB5 silencing in ER-positive cells significantly decreased cell proliferation and anchorage-independent cell growth. In contrast, overexpression of HOXB5 displayed EMT characteristics with a greater invasive ability, higher cell proliferation and colony formation in soft agar. HOXB5 knockdown or overexpression led to changes in the expression levels of RET, ERBB2, and EGFR, but not of ESR1. In conclusion, we suggest that HOXB5 acts as a positive modulator most likely by promoting cell proliferative response and invasiveness in ER-positive breast cancer. These results would help predict prognosis of breast cancer and identify a new valuable therapeutic target.

Analysis of HOX gene expression patterns in human breast cancer.

HOX genes are highly conserved transcription factors that determine the identity of cells and tissues along the anterior-posterior body axis in developing embryos. Aberrations in HOX gene expression have been shown in various tumors. However, the correlation of HOX gene expression patterns with tumorigenesis and cancer progression has not been fully characterized. Here, to analyze putative candidate HOX genes involved in breast cancer tumorigenesis and progression, the expression patterns of 39 HOX genes were analyzed using breast cancer cell lines and patient-derived breast tissues. In vitro analysis revealed that HOXA and HOXB gene expression occurred in a subtype-specific manner in breast cancer cell lines, whereas most HOXC genes were strongly expressed in most cell lines. Among the 39 HOX genes analyzed, 25 were chosen for further analysis in malignant and non-malignant tissues. Fourteen genes, encoding HOXA6, A13, B2, B4, B5, B6, B7, B8, B9, C5, C9, C13, D1, and D8, out of 25 showed statistically significant differential expression patterns between non-malignant and malignant breast tissues and are putative candidates associated with the development and malignant progression of breast cancer. Our data provide a valuable resource for furthering our understanding of HOX gene expression in breast cancer and the possible involvement of HOX genes in tumor progression.

Characterization of Enterococcus spp. from human and animal feces using 16S rRNA sequences, the esp gene, and PFGE for microbial source tracking in Korea.

Contamination from human and animal fecal waste is a primary cause of water pollution. Microbial source tracking (MST) may be a useful tool for high-quality environmental management and for assessing human health risks associated with water pollution. The goal of this study was to evaluate Enterococcus spp. as a target organism for MST. Thirty-four fecal samples were collected from five different sources (human, chicken, pig, cow, and goose) in South Korea. In total, 237 Enterococcus spp. were isolated from feces using membrane- Enterococcus indoxyl-beta-d-glucoside agar. The 16S rRNA gene and the whole genome were analyzed using nucleic acid sequencing and pulsed-field gel electrophoresis (PFGE), respectively. Both phylogenetic analysis and principal coordinate analysis using UniFrac were performed on the nucleic acid sequences of the 16S rRNA gene. According to P-tests from UniFrac, significant differences existed between Enterococcus spp. isolated from human feces and those from animal feces. In addition, we evaluated whether the esp gene of Enterococcus faecium could be a specific target for Enterococcus spp. isolated from human feces. Of 58 E. faecium isolates tested, only three were esp-positive. The specificity of the esp gene of E. faecium isolated from human feces was 100%, but the sensitivity was <10%. These results suggest that Enterococcus spp. have different molecular characteristics according to their fecal source and that these characteristics can be further identified by analyzing the esp gene and 16S rRNA sequences, whereas PFGE provides limited information on the fecal sources of Enterococcus spp.

Solution structure of peptide AG4 used to form silver nanoparticles.

The preparation of silver nanoparticles (AgNPs) is of great interest due to their various biological activities, such as observed in their antimicrobial and wound healing actions. Moreover, the formation of AgNPs using silver-binding peptide has certain advantages because they can be made in aqueous solution at ambient temperature. The solution structure of the silver-binding peptide AG4 was determined using nuclear magnetic resonance spectroscopy, and the site of the AG4 interaction with AgNPs was elucidated.