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Introduction: To date, the role of immunotherapy with check point inhibitors and/or vaccines in the treatment of breast cancer (BC) is still debating, and the main focus of immunotherapy in BC is on triple negative subtype as a target population in many ongoing clinical trials. Translational research into identifying predictive and prognostic immune biomarkers is of particular clinical relevance, but, there are currently no definite prognostic and predictive immune biomarkers in BC, especially in triple negative breast cancer(TNBC). We investigated the expression profiles of immune genes in patients with TNBC to identify the prognostic value of immune genes in search of clinical implications. Methods : We investigated expression profiles of 770 pan-cancer immune related genes using the nCounter mRNA expression assay (NanoString®) from paraffin-embedded tumor tissues in 200 patients diagnosed as TNBC who received curative surgery at Samsung Medical Center from 2000 to 2004. We analyzed the relationship between stage adjusted level of gene expressions and patients' survival outcomes using Cox regression model. Results: Of 770 genes, 186 genes were selected from univariate analysis with clinical stage adjustment. In multivariate analysis using Cox regression, expressions of CD1B, CD45, CD53, CT45A1, GTF3C1, IL11RA, IL1RN, LRRN3, MAPK1, NEFL, PRKCE, SPACA3 and RANKL were associated with distant recurrence free survival (p Table 1ParameterParameter EstimateStandard Errorp-valueHazard Ratio95% Confidence Interval(a) distant recurrence free survival Stage2.487350.680570.000312.0293.169, 45.661CD1B1.141910.2753 Conclusion: High expression of IL1RN, PRKCE were associated with short distant recurrence free survival and overall survival in patients with TNBCs who received curative surgery. In contrast, RANKL expression resulted in prolonged distant recurrence free survival and overall survival. Citation Format: Kim J-Y, Jung HH, Lim JE, Cho EY, Lee SK, Yu JH, Lee JE, Kim SW, Nam SJ, Park YH, Ahn JS, Im Y-H. Prognostication of immune related gene expression in patients with triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-08-30.

Introduction: PIK3CA mutation is one of the most frequent genomic alterations in breast cancer. We evaluated PIK3CA mutational status including spatial and temporal heterogeneity, clinical characteristics and prognostic impact focused on ER+/HER2- subtype. Methods: We performed targeted ultra-deep sequencing (CancerSCAN™) of breast cancer tissue in a prospective cohort. Burden of disease was assessed by metabolic tumor volume(MTV) in 18F-FDG-PET scan. Association with clinical characteristics or survival were tested in ER+/HER2- subtype, using Chi square test or Kaplan-Meier method. Results: PIK3CA analyses were performed in 1274 breast cancer specimens from 1091 patients. 957 patients had early breast cancer. PIK3CA alterations were found in 397 patients(36.3%), and frequency of PIK3CA mutation was significantly lower in triple negative breast cancer(19.0%), compared with 40.4% in ER+/HER2-, 40.9% in ER+/HER2+, and 45.2% in ER-/HER2+ subtype(p Conclusion: We observed variations in PIK3CA mutational status in more than 10% of patients with >1 repeated biopsy. In stage IV ER+/HER2- disease, PIK3CA hotspot mutation seemed to be associated with longer PFS and OS, however metabolic tumor burden was not associated with PIK3CA alterations. Citation Format: Ahn HK, Park S, Hyun SH, Park K, Lee E, Kim J-Y, Nam SJ, Kim SW, Lee JE, Lee SK, Yu JH, Ahn JS, Im Y-H, Park YH. PIK3CA mutations in breast cancer: Mutational landscape and clinical implications in ER+/HER2- subtype [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-08-12.

Introduction: Genetic alteration of Estrogen Receptor 1(ESR1) gene have been associated with acquired endocrine resistance and occurred in about 20% of endocrine resistant estrogen receptor(ER)-positive metastatic breast cancer(MBC). Mutations in ligand binding domain of ESR1 lead to constitutive activity of the ER without ligand estrogen and stimulated down stream cell growth signal. Therefore, ESR1 ligand binding domain alteration is known resistant mechanism of aromatase inhibitor. Among these ESR1 mutations, Y537S, one of the ligand binding domain mutations, caused ER antagonist, fulvestrant resistance. Therefore, assessment of ESR1 mutation in ER-positive MBC had significant benefit to further precision medicine for MBCs. In this study, we explored to identify the frequency and type of ESR1 genetic alterations of ER-positive MBC. Methods: We performed targeted ultra-deep sequencing (CancerSCAN™) using BC tissue specimens. This sequencing was covered entire coding area of ESR1 gene and also detected copy number alteration and translocation of ESR1. Results: Targeted ultra-deep sequencing of ESR1 was performed using 990 BC tissues. Of 990 tissue samples, 341(34.5%) were MBCs. Of MBCs, 112(11.3%) were ER-positive and human epidermal growth factor receptor 2(HER2)-negative BCs. In ER-positive HER2-negative MBCs (N=112), 21 ESR1 genetic alterations were identified in 19 BCs (17.0%). Nineteen were single nucleotide variats (SNVs) and three were copy number (CN) amplification. Most commonly detected single nucleotide variant (SNV) was D538G (6 of 19, 31.6%) followed by Y537N, Y537S, V382I (4, 2 and 2 cases, respectively). Three mutations occurred in non-ligand binding domain (G415V, V392I and P79A). Two BC samples harbored two ESR1 mutations, respectively (Y537S and D538G, L536P and Y537N). In terms of treatment, 11 of 12 patients with ER-positive MBC harboring ESR1 mutation received palliative endocrine therapies. Eight patients received aromatase inhibitor and two patients received tamoxifen. One patient received letrozole plus palbociclib. In 2 MBCs with Y537S mutation, progression free survival (PFS) of endocrine therapy was 1.4 and 5.3 months. MBCs with D538G had 12.3months of PFS (range, 5.3-23.7(months)) and BCs harboring another ligand binding domain mutations (Y537N, L536H and L536P) had 15.7months of PFS of endocrine therapy (range, 8.4-17.3(months)). BC with mutation observed in non-lignand binding domain had short PFS (1.8 (V392I) and 2.7 (P79A) months, respectively). In terms of ESR1 CN amplification, patients could not receive endocrine therapy because their BCs rapidly progressed and extensive distant metastases were occurred within 3 months after curative surgery. Conclusion: In this exploratory study, ESR1 genetic alterations were detected in about 20% of ER-positive MBC. The type of genetic alterations varied including SNVs, CNAs. Each locus of ESR1 mutation predicted endocrine resistance. In addition, we might suggest that ESR1 CN amplification is prognostic marker of ER-positive BCs. Citation Format: Kim J-Y, Park KH, Park W-Y, Nam SJ, Kim SW, Lee JE, Lee SK, Yu JH, Ahn JS, Im Y-H, Park YH. Prognostication of genetic alterations of ESR 1 in estrogen receptor positive metastatic breast cancers using targeted ultra-deep sequencing data analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-09-11.

This abstract was not presented at the conference. Citation Format: Choi HJ, Kim SW, Ryu JM, Kim I, Nam SJ, Yu J, Lee SK, Lee JE. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-18.

Understanding how standard-of-care drug treatments affect tumor intrinsic biology and microenvironment is critical for elucidating drug resistance mechanisms and developing better combination therapies as well as new therapies. To characterize the effects of neoadjuvant chemotherapy (NAC) on the genome, transcriptome and tumor infiltrating leukocytes (TILs), we have conducted whole exome and whole transcriptome sequencing of a large longitudinal breast cancer cohort consisting of 146 cases and 281 paired tumor samples. In total, 52 (38%) patients achieved pathologic complete response (pCR) while 85 patients (62%) had residual disease with standard chemotherapy regimen. Tumor biopsies were collected for each patient at three time points – pre-treatment, three weeks after the first cycle of anthracycline and cyclophosphamide (AC) and at the time of surgery after 3 more cycles of AC followed by 4 cycles of taxane or taxane plus Herceptin in case of HER2+ subtype. We detected 5,955 protein-altering somatic mutations affecting 4,414 genes in pretreatment samples and 502 acquired mutations in surgery samples affecting 477 genes including 19recurrently mutated genes such as TP53 and NOTCH1. Across all subtypes, 4,346 genes were differentially expressed (DE) following NAC treatment and significantly enriched in pathways such as cell cycle, ER signaling, PI3K/mTOR, immune and metabolism. Expression-based virtual microdissection analysis indicated that NAC treatment induced an increase in the fractions of stromal and adjacent normal tissue compartment, consistent with observed reduction in tumor cellularity. To assess the NAC induced changes in the molecular landscape of these tumors, we compared molecular features including gene expression signatures, mutation prevalence and copy number alteration between three time points while adjusting for confounding effects of molecular subtype and tumor cellularity. We found that NAC induced dynamic changes in gene expression signatures associated with proliferation and immunomodulatory treatment response. We further validated the observed pattern of change in TILs through histopathology and digital imaging analyses. In pretreatment tumors, 116 genes were DE between patients with pCR vs. those with residual disease with significant enrichment in immune/inflammatory pathways. Further, pre-treatment TIL levels were found to be significantly associated with pCR, echoing previous reports in breast cancers that implicated anti-tumor immunity in mediating the efficacy of chemotherapies. Our analyses also revealed associations between NAC response and baseline genomic attributes such as genomic alterations that affect DNA damage repair pathways. Taken together, these results suggest that NAC induced a multitude of changes on the genomic landscape and immune microenvironment of breast cancers, some of which point to combination strategies with immunomodulatory therapies and therapies that target DNA damage repair. Citation Format: Kan Z, Lal S, Ding Y, Lee JE, Lee S-H, Lee SK, Yu JH, Choi Y-l, Kim SW, Nam SJ, Kim J-Y, Ram S, Powell E, Ching K, Cho SY, Bonato V, Deng S, Park W-Y, Rejto P, Bienkowska J, Park Y-H. Neoadjuvant chemotherapy alters the genomic landscape and immune microenvironment of breast cancers [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr PD5-08.

Introduction Soft tissue augmentation using hyaluronic acid (HA) filler has grown rapidly in recent years, while clinical studies, especially randomized control trial, in penile augmentation (PA) using HA filler rarely conducted. Objective This study aimed to investigate the efficacy and safety of HA filler injection for temporary PA as compared to polylactic acid (PLA) filler. Methods The present prospective, patient/evaluator-blinded, multi-center study randomized 74 patients with small penis syndrome, which defined as the anxiety felt when one's penis is being observed because of concern that the penis is small, to HA filler injection or PLA filler injection for PA. Penile girth and satisfaction, were assessed at baseline and at 4, 12, and 24 weeks after injection. Safety profile evaluation was extended for 48 weeks for HA filler injection group. Results Grossly, both filler materials were evenly distributed, and led to a significant volume expansion for up to 24 weeks post-injection (Figure 1) In both group, mean penile girths significantly increased at 4 weeks post-injection (2.7±1.0 and 2.3±1.1 cm mean increases in the HA and PLA groups, respectively; each p Conclusion HA filler was similarly effective with PLA filler for temporary PA in men with small-penis syndrome and can be used safely for a long time until 48 weeks.

Purpose Numerous studies demonstrated that breast cancer in young women (BCY) has unfavorable prognostic features and unfavorable subtype. However, there were few studies to evaluate the effect on the prognosis of breast cancer according to the subtype disparities by age especially BCY. We analyzed breast cancer mortality stratified tumor subtype according to age among the patients with less than 50 year-old. Patients and Methods Data obtained from the Korean Breast Cancer Society Registry (KBCSR), patients diagnosed with invasive breast cancer were retrospectively between 2003 and 2010. We excluded patients with male breast cancer, underwent neoadjuvant chemotherapy, distant metastasis or inflammatory breast cancer at presentation, and other histopathology except invasive ductal or invasive lobular carcinoma. We also excluded patients with lack of immunohistochemistry data and short-term follow-up duration ( Table 1. Baseline Characteristics Age at Presentation 20-29, N(%)30-39, N(%)40-49, N(%)P-valueOverall793 (2.6)8,133 (26.4)21,867 (71.0) Pathologic stage . Patients with younger age group showed worse prognosis than patients with older age patients. In multivariate analysis for overall survival, as patients were younger group, hazard ratio was increased, and the patients with TNBC showed higher HR than HER-2, Luminal B, and Luminal A subtype (P< .0001, P< .0001, P< .0001, and P< .0001, respectively). Stratified by subtype, luminal subtype showed significant worse prognosis as the age group was younger, while as, Her-2 and TNBC subtype showed no significantly difference by the age group. Conclusion Patients with 20s breast cancer showed unfavorable characteristics and worse prognosis than 30s and older aged group. Stratified by tumor subtype, breast cancer in 20s with luminal subtype showed worse prognosis, while as HER-2 and TNBC showed no significantly different compare to breast cancer in 30s. Citation Format: Ryu JM, Yu J, Nam SJ, Kim I, Lee JE, Lee SK, Kim JM, Choi HJ, Kim SW. Differences among young breast cancer patients based on subtype: A study from the Korean Breast Cancer Society – Running head: Do breast cancers in 20s have worse prognosis than 30s? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-25.

Introduction : Our understanding of biology of breast cancer has led to significant changes in diagnostic and therapeutic approaches for breast cancer, The new eighth edition of the TNM classification of the AJCC for breast cancer (BC) determined by a multidisciplinary team of BC experts incorporate biologic factors, such as tumor grade, estrogen and progesterone receptor (ER and PR) expression, human epidermal growth factor 2 (HER2) expression, and gene expression prognostic panels in addition to traditional anatomic factors. In this study, we aimed to evaluate prognostic value of this new staging system compared to previous AJCC 7th staging system using single center, long term followed BC cohort. Methods : We conducted a retrospective analysis of women with stage I, II, or III BC who underwent curative surgery with/without adjuvant systemic therapy at Samsung Medical Center between July 2004 and December 2008 (n=3,029). We excluded patients who received neoadjuvant therapy (n=183), and patients with missing information about immunohistochemistry (n=7), HER2 status (n=82) or histologic grade (n=74). The final sample size was 2,683. Results: Of 2,683 BCs, 1,689 (63%) were hormone receptor (HR)-positive(+), 244(9%) were HR+ andHER2+, 289(11%) were HR-negative(-) andHER2+, 461(17%) were triple negative BCs. According to AJCC 7th pathologic staging system, there were 1,135 of stage IA, 4 of IB, 803 of stage IIA, 368 of stage IIB, 258 of stage IIIA, 11 of stage IIIB and 104 of stage IIIC. In terms of 10 year overall survival (OS) according to AJCC 7th staging system, 95.8% in stage IA, 100% in stage IB, 93.5% in IIA, 86.0% in stage IIB, 85.6% in stage IIIA, 90.9% in stage IIIB and 63.6% in stage IIIC were observed (p Conclusions: AJCC 8th clinical staging system provides a good prognostic value and makes up for the weakness of AJCC 7th anatomical pathologic staging. But this system cannot count whole pathologic stages. Modification of AJCC 8th clinical staging system would be warranted. Citation Format: Kim J-Y, Lim JE, Jung HH, Cho SY, Cho EY, Lee SK, Yu JH, Lee JE, Kim SW, Nam SJ, Park YH, Ahn JS, Im Y-H. Validation of the new AJCC eighth edition of the TNM classification for breast cancer with a single center breast cancer cohort [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-32.

Introduction: Estrogen Receptor 1 (ESR1) gene encodes an estrogen receptor, which regulates cell proliferation and promotes tumor progression in estrogen receptor(ER)-positive breast cancer (BC). Therefore, endocrine therapy that inhibiting ER downstream signal, is the most effective treatment strategy in ER-positive BC. However, about 25% of patients with primary disease and almost all patients with metastases will present with or eventually develop endocrine resistance. And genetic alteration of ESR1 is now identified as the endocrine resistance mechanism. However, a few data from clinical trials or public data base exists and could not reflect real world clinic. Therefore, we aimed to identify the frequency and type of ESR1 genetic alterations in BCs through this large scaled study. Methods: We performed targeted ultra-deep sequencing (CancerSCAN™) using BC tissue specimens. This sequencing was covered entire coding area of ESR1 gene and also detected copy number alteration and translocation of ESR1. Results: Targeted ultra-deep sequencing of ESR1 was performed using 618 BC tissues. Of 618 tissue samples, 253(40.9%) were MBCs, 362(58.6%) were early BCs (EBCs) and 3 were not identified. In terms of subtypes, 220 ER-positive BCs, 122 ER-positive and HER2-positive BCs, 119 HER2-positive and 153 triple-negative BCs (TNBCs) were included. BCs from patients under 40 year-old were 277(44.8%)(Median: 43.0, range: 23.5 -75.6). ESR1 genetic alterations were identified in 21 BCs (5 EBCs and 16 MBCs). In EBCs, 3 cases were observed in TNBCs and 2 cases were in ER-positive BCs (2.6% and 1.2%, respectively). All five EBC were treatment naïve status. Of 16 cases of ESR1 alterations in MBCs, 10 cases of ESR1 alterations were detected in ER-positive BCs (17.6%), 5cases in ER and HER2-positive BCs(6.7%) and 1 in HER2-positive BCs (1.2%). All ER-positive MBCs were treated with more than one line of endocrine therapy. Most commonly detected genetic alteration was single nucleotide variant (SNV) (15 of 21, 71.4%). Thirteen were in ligand binding domain and two cases occurred in activation function-1 (AF-1) domain (P79A and G145S). D538G and V392I were most frequently mutated loci followed by Y537N (3, 3 and 2 cases, respectively) and only metastatic ER-positive BCs harbored ESR1 activating mutation. Four copy number (CN) amplification in 2 ER-positive and 2 ER and HER2-positive BCs, one CN deletion in TNBC and one ESR1 fusion in ER and HER2-positive BC were also detected (19.0%, 4.8% and 4.8%, respectively). In frame ESR1 fusion was occurred between ESR1 and NPHS1 genes. Conclusion: In this experimental study, ESR1 genetic alterations were frequently detected in ER-positive MBC but ER-negative or EBC also harbored. The type of genetic alterations varied including SNVs, CN alterations and translocation and ESR1-NPHS1 fusion is the novel genetic alteration that has not been reported. To identify the role of ESR1 genetic alteration in ER-negative BCs and novel translocation, further functional validation would be warranted (Clinical trials.gov Number :NCT02591966). Citation Format: Kim J-Y, Park K, Park W-Y, Nam SJ, Kim SW, Lee JE, Lee SK, Jung HH, Yu JH, Ahn JS, Im Y-H, Park YH. Identification of ESR1 mutation in breast cancers using targeted ultra-deep sequencing data analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-09-08.

Objectives The aim was to evaluate the importance of clinical factors in the prediction of postoperative complications in patients with microvascular reconstruction for head and neck squamous cell cancer (HNSCC). Design A retrospective review of case notes was performed. Setting Patients treated at a single institute. Participants This study included 259 patients with HNSCC treated with radical surgery and microvascular reconstruction between 1993 and 2014. Main outcome measures We allocated the patients to three groups using a preoperative comorbidity score based on risk factors: group A (≥3 risk factors, n = 16), group B (2 risk factors, n = 49) and group C (0 or 1 risk factor, n = 194). Results Surgical mortality in this cohort was 1.9% (5 of 259 patients). The preoperative comorbidity score was associated with surgical mortality (P < .001). Pharyngocutaneous fistula (P = .001) and flap compromise (P = .023) were more frequent as preoperative comorbidity score increased. Preoperative comorbidity score (P < .001), advanced age (P = .007), advanced pathologic T stage (P = .028), advanced pathologic N stage (P = .005), preoperative (chemo) radiotherapy (P < .001), history of cardiovascular disease (P = .015) and pulmonary disease (P = .007), and diabetes (P < .001) had significant adverse effects on 5 year disease-specific survival (DSS) in a univariate analysis. The 5-DSS rates of groups A, B and C were 30%, 37% and 70%, respectively. Multivariate analysis showed that preoperative comorbidity score was significantly correlated with 5 year DSS (hazard ratio [HR], 3.56; 95% confidence interval [CI], 1.81—6.99; P < .001 for group A and HR, 1.91; 95% CI, 1.15—3.18; P = .013 for group B compared with group C). Conclusion Patients with a high preoperative comorbidity score have an increased risk of surgical mortality and morbidity after microvascular reconstruction for HNSCC.

Objective:This study aimed to identify the effect of lateral neck dissection on voice change in thyroidectomised patients.Methods:Medical records from 264 patients who underwent thyroidectomy with (n= 65) or without (n= 199) lateral neck dissection were reviewed. Clinical and voice evaluation data were compared between the two groups.Results:Patients who underwent surgery that included lateral neck dissection had lower fundamental frequencies and speaking fundamental frequencies. They also had a higher incidence of asymmetric mucosal wave and vocal fold oedema on videostroboscopy during the first month after surgery, with the incidence of vocal fold oedema remaining significantly higher at three months. Self-assessed voice quality scores were significantly higher in lateral neck dissection patients at both one and three months after surgery.Conclusion:In thyroidectomised patients, lateral neck dissection lowers the vocal pitch in the initial period after surgery and induces vocal fold oedema that persists for several months. Although most objective parameters improved within a month, subjective symptoms lasted for longer.

Breast cancers (BC) in younger, premenopausal patients (YBC) tend to be more aggressive with worse prognosis, higher chance of relapse and poorer response to endocrine therapies compared to breast cancers in older patients. The proportion of YBC (age ≤ 40) among BC in East Asia is estimated to be 16-32%, significantly higher than the 7% reported in Western countries. To characterize the molecular bases of Asian YBC, we have performed whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) on tumor and matched normal samples from 134 Korean BC patients consisting of 74 YBC cases (age ≤ 40) and 60 OBC cases (age > 40). We then performed comparison analyses and integrative analyses with the TCGA BC cohort consisting of 1,116 tumors from primarily Caucasian patients, also grouped by age into YBC (age ≤ 40), IBC (40 < age ≤ 60) and OBC (age > 60). Somatic mutation prevalence analysis identified 7 significantly mutated genes and the same top three genes – TP53, GATA3 and PIK3CA – were reported by the TCGA BC study. To identify differentially expressed (DE) genes and pathways in YBCs vs. OBCs, we performed logistic regression analyses while controlling for the confounding effects of tumor purity and stage. We were surprised to see a significant overlap in DE pathways between a comparison of adjacent normal tissues in younger vs. older TCGA cohorts and a comparison of YBC vs. OBC tumors, indicating that normal tissue compartment could contribute to observed differences between bulk tumors. To separately examine molecular signatures from tumor, stroma and normal compartments, we used non-negative matrix factorization (NMF) analyses to virtually dissect bulk tumor expression data and identified 14 factors including 3 factors associated with normal tissues, 1 factor associated with stroma and 1 factor associated with tumor infiltrating lymphocytes (TIL). Integrative analyses of tumor associated factors and DE pathways revealed that estrogen response, endocrine therapy resistance, and oxidative phosphorylation pathways are up-regulated in YBCs compared to OBCs while cell cycle and proliferation pathways are up-regulated in Asian OBCs. Interestingly, many immune and inflammation pathways correlated with the TIL factor were significantly upregulated in OBCs vs. YBCs. Using gene expression signatures representing distinct immune cell types, we classified our cohort into four subtypes of varying TIL activities and observed significant enrichment of the TIL-high subtype in OBCs compared to YBCs. These observations were confirmed by IHC analyses of four TIL markers (CD45, CD4, CD8 and CD163) in 120 tumors. To our knowledge, this is the first large-scale multi-omics study of Asian breast cancer and would significantly contribute to the compendium of molecular data available for studying young breast cancers. The major landmarks in the molecular landscape looked similar across BCs of different ethnicities and ages, however, we have identified a number of distinguishing molecular characteristics associated with Asian YBC. The sources for some signatures were further traced to non-tumor intrinsic compartments, indicating that tumor microenvironment may play potentially important roles in driving the carcinogenesis of young breast cancers. Citation Format: Kan Z, Ding Y, Cho S, Lee S-H, Powell E, Jung HH, Chung W, Deng S, Choi Y-l, Kim J, Park W-Y, Vizcarra P, Fernandez-Banet J, Nichols T, Ram S, Lee SK, Kim SW, Lee JE, Ching KA, Kim J-Y, Ahn JS, Im Y-H, Nam SJ, Park YH. Multi-omics and immuno-oncology profiling reveal distinct molecular signatures of young Asian breast cancers [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-15.

Background: Conditional disease-free survival (CDFS) reflects changes over time. Because traditional disease-free survival (DFS) is estimated from the date of diagnosis, it is limited in the ability to predict risk of recurrence in patients who have been disease free. In this study, we determined CDFS of breast cancer patients and estimated the prognostic factors for DFS. Method: We retrospectively reviewed clinical data of 7587 consecutive patients who underwent curative surgery for breast cancer between January 2004 and December 2013 at Samsung Medical Center. Univariate and multivariate analyses were performed to identify risk factors for DFS, which was computed using the Kaplan–Meier method. CDFS rates were based on cumulative DFS estimates. Results: Median follow-up duration was 20.44 months. Three-year DFS was 93.46 percent at baseline. Three-year CDFS survival estimates for patients who had been disease free for 1, 2, 3, 4 and 5 years after treatment were calculated as 92.84, 92.37, 93.03, 89.41, and 79.64 percent, respectively. Three-year CDFS increased continuously each year after 1 year of DFS in hormone receptor (HR)-negative patients but decreased each year in HR-positive patients. Conclusion: In HR-positive patients who are disease free after 3 years, continuous care including surveillance and metastases workup should be considered, although this is not recommended in the current guidelines. On the other hand, the social costs may be reduced in HR-negative patients by extending the surveillance interval. Further studies are needed to identify indicators of DFS prognosis in breast cancer patients.Background: Conditional disease-free survival (CDFS) reflects changes over time. Because traditional disease-free survival (DFS) is estimated from the date of diagnosis, it is limited in the ability to predict risk of recurrence in patients who have been disease free. In this study, we determined CDFS of breast cancer patients and estimated the prognostic factors for DFS. Method: We retrospectively reviewed clinical data of 7587 consecutive patients who underwent curative surgery for breast cancer between January 2004 and December 2013 at Samsung Medical Center. Univariate and multivariate analyses were performed to identify risk factors for DFS, which was computed using the Kaplan–Meier method. CDFS rates were based on cumulative DFS estimates. Results: Median follow-up duration was 20.44 months. Three-year DFS was 93.46 percent at baseline. Three-year CDFS survival estimates for patients who had been disease free for 1, 2, 3, 4 and 5 years after treatment were calculated as 92.84, 92.37, 93.03, 89.41, and 79.64 percent, respectively. Three-year CDFS increased continuously each year after 1 year of DFS in hormone receptor (HR)-negative patients but decreased each year in HR-positive patients. Conclusion: In HR-positive patients who are disease free after 3 years, continuous care including surveillance and metastases workup should be considered, although this is not recommended in the current guidelines. On the other hand, the social costs may be reduced in HR-negative patients by extending the surveillance interval. Further studies are needed to identify indicators of DFS prognosis in breast cancer patients. Citation Format: Paik H-J, Lee SK, Park S, Ryu JM, Kim I, Bae SY, Yu J, Lee JE, Kim SW, Nam SJ. Conditional disease-free survival among patients with breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-13-07.

Introduction:Substantial efforts have been made to find factors associated with breast cancer (BC) recurrence and mortality after BC treatment. So far TNM stage, ER, PR, and HER2 status are considered as the major predictive markers of BC recurrence and used for treatment decision. However, most of these factors were evaluated independent from other important confounders such as age, stage, and various anti-cancer treatments because they were mostly derived from clinical trials. In Korea, up to 50% of BC patients are premenopausal women, it is not clear how age at diagnosis affect the progression and outcomes of the disease considering all known prognostic factors including TNM stage, ER, PR, and HER2 status. We aim to evaluate the impact of young age on recurrence and mortality after surgery among Korean women with BC. Methods: This is a retrospective cohort study conducted using the data from BC registry from 2000 to 2016 at Samsung Medical Cancer, Seoul, Korea. Patients who received curative BC surgery and who had histologically-confirmed invasive BC between 2000 to 2011 were included in the study. Patients who second primary cancer or double primary cancer were excluded. Information local, regional, or distant recurrence and death until May 2016 was collected using electronic medical records and National Health Statistics. Cumulative incidence rates of distant recurrence and morality at 3-years, 5-years and 10-years were calculated using a competing-risk model. Cox proportional hazards analysis were conducted with 3 different models to take into account for potential confounding factors including age, body mass index (BMI), stage and subtype at breast cancer diagnosis, chemotherapy, radiotherapy and hormone therapy. Results:There were 7360 BC patients with curative BC surgery between 2000 and 2011, and the average follow up duration was 75.4 months. The mean age at diagnosis was 48.4 years old (Standard deviation (SD)=±10), and 6.2% (n=459) was diagnosed younger than 35. Of total, 13.3% were stage III BC and 73.4% of patients had hormone receptor positive BC. The cumulative incidence (95%CI) of recurrence at 3, 5, and 10 years was 4.4% (3.9-4.9), 7.5% (6.8-8.2), and 14.8% (12.9-16.7) respectively. The incidence of mortality at 3, 5, and 10 years was 1.8% (1.5-2.1), 3.8% (3.3-4.3), and 10.2% (9.1-11.5) respectively. Patients who were diagnosed BC under 35 years of age had 2.14 (95% confidence interval (CI):1.74-3.10) and 1.62 (95% CI:1.02-2.56) times higher risk of distant recurrence and mortality compared to patients whose age at diagnosis were between 50 to 60 after adjusting all well-known prognostic factors including stage, subtype, and BMI at diagnosis, chemotherapy, radiotherapy and hormone therapy. Conclusions: Young age at diagnosis ( Citation Format: Kim J-Y, Cho J, Kim H, Kang D, Jung HA, Lee S-H, Bae S, Yu JH, Lee SK, Kim SW, Lee JE, Nam SJ, Ahn JS, Im Y-H, Guallar E, Park YH. Impact of young age on recurrence and mortality after surgery in breast cancer: 15 years active surveillance [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-50.

Setting Despite the clinical importance of idiopathic pulmonary fibrosis (IPF), its epidemiology has been rarely reported. The economic burden from IPF is therefore difficult to predict. Objective To analyse the health care burden and current situation with respect to medical resource utilisation in patients with IPF in Korea. Methods We analysed nationwide data collected between 2009 and 2013 from the Korean Health Insurance Review and Assessment (HIRA) database. Patients with IPF were defined by the K-J84.18 code of the Korean Classification of Disease, 6th revision. Results The total direct health care costs increased from US$19 805 167 in 2009 to US$31 410 083 in 2013; the principal factor responsible for the highest proportion of costs was hospitalisation. The proportion of the total IPF patient population who were hospitalised at least once a year was 27.2%, and the average length of hospital stay was 12.7 days. From post-hoc analysis, hospital admission, emergency room visit and intensive care unit admission rates showed significant seasonal variations; the admission rates were highest in the spring and lowest in autumn. Conclusions Health care costs of IPF are increasing annually, with hospital admissions representing the major financial burden.

Introduction/Background This study evaluated the oncologic and pregnancy outcomes of progestin treatment for early endometrial cancer in young women. Methodology We retrospectively analyzed the medical records of 82 patients younger than 45 years with early stage endometrial cancer who had received fertility-sparing management between 2006 and 2018. All of the patients were treated with medroxyprogesterone acetate (MPA) or megestrol acetate (MA) or combined MPA/levonorgestrel-intrauterine system (LNG-IUS). Results Fifty-nine patients (72.0%) showed complete response (CR) after progestin therapy, and 19 (32.2%) of them experienced recurrence after median follow-up time of 29.2 months. Age ≥35 (p=0.011), body mass index (BMI) ≥25 (p=0.015), and myometrial invasion (p=0.002) were significantly negative factors associated with achieving CR. Multivariate analysis showed that myometrial invasion (hazard ratio [HR]=14.00, 95% confidence interval [CI] 2.45–80.14, p=0.003) was significantly associated with a higher risk of recurrence and maintenance treatment (HR=0.26, 95% CI 0.08–0.85, p=0.026), and assisted reproductive technology (ART) utilization (HR=0.20, 95% CI 0.06–0.66, p=0.008) were significantly associated with a lower risk of recurrence. Of the 24 (40.7%) patients who tried to conceive after CR, 21 (87.5%) patients underwent ART, 12 (50.0%) patients experienced pregnancy, 9 patients (75.0%) had live newborn infants. Conclusion Fertility-sparing management for early endometrial cancer with progestin is significantly effective. Patients with maintenance treatment, ART utilization, and without myometrial invasion associated with a higher probability of long-term success. Disclosure Nothing to disclose.

Introduction/Background With an increase in demand for less-invasive surgeries, the role of laparoscopic surgery in the management of gynecological cancers continues to expand. However, the scope of single port laparoscopy is still limited in ovarian cancer. We reported the experience of single port access (SPA) laparoscopic staging of early stage ovarian cancer. Methodology We prospectively collected data on women who had SPA laparoscopic staging surgery at Severance Hospital between 2014 and 2017. The surgical outcomes, including intra-operative data, time to interval between the end of SPA laparoscopy and postoperative adjuvant chemotherapy (POAC), and port related complications were measured. Results Fifty six patients underwent SPA laparoscopic staging surgery. Mean patient age and BMI were 47.25±13.93 and 23.58 kg/m2±3.24, respectively. Mean operation time was 235±93 minutes and median blood loss was 55 ml (range, 10–1100). Median time interval between the end of procedure and the start of POAC was 21 days (range, 14–31). Additional port was needed in 4 cases (7.1%) and the conversion rate to laparotomy was 8.9%. There were no peri-operative moderate to severe complications, including port-site metastasis. The upstaging rate after SPA laparoscopic staging surgery was 30.3% and POAC was performed in 34 cases (60.7%). The overall rate of recurrence with a median follow up period of 26 months was 16% (9 cases) and 4 patients died due to the disease. Conclusion The surgical outcomes of SPA laparoscopic staging surgery in patient with early stage ovarian cancer is feasible and could be compatible with conventional laparoscopic approach in terms of operative outcomes and upstaging rate in comparison with previous studies. Disclosure Nothing to disclose.

Summary Background Endocrine treatment is recommended by clinical guidelines as the preferred treatment option for premenopausal as well as postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. In real-world clinical practice, however, a substantial number of patients are treated with chemotherapy. We aimed to compare the clinical antitumour activity and safety of palbociclib plus endocrine therapy with that of capecitabine chemotherapy in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer. Methods This multicentre, open-label, randomised, phase 2 study was done in 14 academic institutions in South Korea. Premenopausal women aged 19 years or older with hormone receptor-positive, HER2-negative breast cancer that had relapsed or progressed during previous tamoxifen therapy and with an Eastern Cooperative Oncology Group performance status of 0–2 were included. One line of previous chemotherapy for metastatic breast cancer was allowed. Patients were randomly assigned, using a random permuted block design (with a block size of two), to receive palbociclib plus combination endocrine therapy (oral exemestane 25 mg per day for 28 days and oral palbociclib 125 mg per day for 21 days every 4 weeks plus leuprolide 3·75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1250 mg/m2 twice daily for 2 weeks every 3 weeks). Randomisation was stratified by previous chemotherapy for metastatic breast cancer and visceral metastasis. The primary endpoint was progression-free survival. All analyses were done in a modified intention-to-treat population that excluded patients who did not receive study medication. This study is registered with ClinicalTrials.gov , NCT02592746 , and is ongoing for follow-up of overall survival. Findings Between June 15, 2016, and Dec 10, 2018, 189 patients were enrolled, of whom 184 were randomly assigned to the palbociclib plus endocrine therapy group (n=92) or the capecitabine group (n=92). Six patients in the capecitabine group withdrew from the study before drug administration; therefore, 92 patients in the palbociclib plus endocrine therapy group and 86 patients in the capecitabine group were included in the modified intention-to-treat analyses. 46 (50%) of 92 patients in the palbociclib plus endocrine therapy group and 45 (51%) of 92 in the capecitabine group were treatment naive for metastatic breast cancer. During a median follow-up of 17 months (IQR 9–22), median progression-free survival was 20·1 months (95% CI 14·2–21·8) in the palbociclib plus endocrine therapy group versus 14·4 months (12·1–17·0) in the capecitabine group (hazard ratio 0·659 [95% CI 0·437–0·994], one-sided log-rank p=0·0235). Treatment-related grade 3 or worse neutropenia was more common in the palbociclib plus endocrine therapy group than in the capecitabine group (69 [75%] of 92 vs 14 [16%] of 86 patients). 2 (2%) patients in the palbociclib plus endocrine therapy group and 15 (17%) patients in the capecitabine group had treatment-related serious adverse events. No treatment-related deaths occurred. Interpretation Exemestane plus palbociclib with ovarian function suppression showed clinical benefit compared with capecitabine in terms of improved progression-free survival in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer. Palbociclib plus exemestane with ovarian suppression is an active treatment option in premenopausal patients with hormone receptor-positive, HER2-negative metastatic breast cancer who have been pretreated with tamoxifen. Funding Pfizer, Shinpoong, and Daewoong Korea and Takeda.

Background Gene delivery systems are essentially necessary for the gene therapy of human genetic diseases. Gene therapy is the unique way that is able to use the adjustable gene to cure any disease. The gene therapy is one of promising therapies for a number of diseases such as inherited disorders, viral infection and cancers. The useful results of gene delivery systems depend open the adjustable targeting gene delivery systems. Some of successful gene delivery systems have recently reported for the practical application of gene therapy. Main body The recent developments of viral gene delivery systems and non-viral gene delivery systems for gene therapy have briefly reviewed. The viral gene delivery systems have discussed for the viral vectors based on DNA, RNA and oncolytic viral vectors. The non-viral gene delivery systems have also treated for the physicochemical approaches such as physical methods and chemical methods. Several kinds of successful gene delivery systems have briefly discussed on the bases of the gene delivery systems such as cationic polymers, poly(L-lysine), polysaccharides, and poly(ethylenimine)s. Conclusion The goal of the research for gene delivery system is to develop the clinically relevant vectors such as viral and non-viral vectors that use to combat elusive diseases such as AIDS, cancer, Alzheimer, etc. Next step research will focus on advancing DNA and RNA molecular technologies to become the standard treatment options in the clinical area of biomedical application.

Background The proportion of young age-onset breast cancer in Korea is relatively higher than Western countries. Young breast cancer patients are more likely to suffer from altered appearance due to cancer treatment such as breast disfiguration, hair loss, skin change and experience poor body image. This randomized controlled trial (RCT) is designed to evaluate the effect of mind and beauty education program on body image among breast cancer patients under 40-years old. Methods A total of 109 eligible breast cancer patients aged 18-40 years old, who had surgery and/or chemotherapy within 18 months and who reported poor body image ( Results A total of 54 and 55 patients were assigned to intervention and control group respectively with block randomization. Among the intervention group, 43 participants (79.6%) attended for more than 6 hours of education. Total 46 participants (85.2%) in intervention group and 53 participants (96.4%) in control group completed the questionnaire at visit 2. Mean age of the study population was 35.5 years old and there were 53 (48.6%), 32 (29.3%), 23 (21.1%) stage I, II, and III breast cancer patients respectively. At baseline, none of the socio-demographic, clinical, psycho-social characteristics were different between two groups. While there was no difference with the body image at baseline between intervention (57.69±20.57) and control group (53.09±26.98) (P=0.327), intervention group reported significantly improved body image than control group (EORTC QLQ-BR23 - Intervention; 71.69±20.27 and Control; 55.97±23.07, P Conclusion This study provided evidence supporting that mind and body education program would be beneficial to young women with breast cancer who would suffer from low body image. Active education program and psychosocial support related to altered appearance would help young breast cancer patients to make a smooth transit when they return to usual life. Trial registration: This study is registered in Korean Clinical Research Information Service (CRIS) with registration number KCT0001191. Funding: This study was supported by grants from Amorepacific. Citation Format: Lee JK, Cho J, Park SK, Kim I-R, Yoon J-H, Choi E-K, Cho S-Y, Lee S-K, Lee JE, Kim S, Nam S-J, Park YH, Ahn JS, Im YH. Effect of mind and beauty education on body image among young breast cancer patients: A randomized controlled trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-30.

Background: The MRE11-RAD50-nibrin (MRN) complex participates in pathways of double-strand break induced DNA repair and cell cycle checkpoint control. RAD50 interacts with the MRE11 and NBS proteins, is involved in the maintenance of genomic integrity. The association of RAD50 mutation and breast cancer susceptibility has been reported in European patients. However, the impact of RAD50 mutation on a breast cancer predisposition among Koreans remains uncertain. In the current analysis, we evaluated the incidence of RAD50 mutations among Korean patients with non-BRCA1/2 high-risk breast cancer. Materials and Methods: A total of 247 Korean patients with high-risk breast cancer who tested negative for BRCA1/2 mutation were enrolled. The criteria for high-risk breast cancer were as follows: having a family history of breast or ovarian cancer in any relative; diagnosed at age 40 years or younger; bilateral breast cancer; and male breast cancer. All participants were screened for BRCA1/2 mutations using fluorescent-conformation sensitive capillary electrophoresis (F-CSCE) and traditional sequencing. The entire RAD50 gene of each patient was sequenced using F-CSCE. In silico analyses of the RAD50 variants was performed using PolyPhen-2 and SIFT. Results: There were two novel deleterious mutations in RAD50 (p.Q426X, p.E1271del). These mutations were found in two patients, including one with p.Q426X and the other with p.E1271del. Besides, five sequence variants in RAD50 were identified: four exonic variants (p.I118T, p.R486C, p.L1264F, and p.R1279H) and one intronic variant (c.1246-11T>C). Among the four missense variants, p.R486C and p.L1264F were variants predicted to be deleterious by in silico analyses. Conclusions: We found protein-truncating mutations in RAD50 gene in a small proportion of Korean patients with high-risk breast cancer. The contribution of the mutation to the development of breast cancer should be clarified in further researches. Citation Format: Kim H, Cho D-Y, Choi DH, Jung GH, Shin I, Park W, Huh SJ, Nam SJ, Lee JE, Gil WH, Kim SW. Heterozygous germline mutations in RAD50 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-08-08.

Background Since the consensus-based diagnostic algorithm for intestinal Behcet’s disease (iBD) was proposed by the IBD Study Group of the Korean Association for the Study of Intestinal Diseases, there were few studies regarding the prognosis of iBD according to the diagnostic algorithm. Methods We reviewed the medical records of patients who had ileocecal ulcers with clinical impression of iBD from March 1986 to August 2019 in Seoul St. Mary’s Hospital and evaluated factors at the time of diagnosis which were related with adverse events (AEs, major operation or admission from iBD) and disease-free survival (DFS). Results Among 204 eligible patients, a total of 163 were included in the study after exclusion of 41 patients with ileocecal ulcers from other disorders. The male-to-female ratio was 1:1 and the mean age at the time of diagnosis was 48.9 ± 15.9. The number of definite, probable, suspected, and non-diagnostic iBD was 18 (11.0%), 64 (39.3%), 37 (22.7%), and 44 (27.0%), respectively. Patients with definite, probable, and suspected iBD developed more AEs compared with patients with non-diagnostic iBD (p = 0.026). After exclusion of patients with non-diagnostic iBD, univariate analysis showed accompanying haematologic disorders, haemoglobin Conclusion Patients with definite, probable, and suspected iBD have a poor prognosis compared with patients with non-diagnostic iBD. Accompanying with haematologic disorders, anaemia, fever, and colonic involvement at the time of diagnosis are poor prognostic factors in patients with iBD.

Background Although immune checkpoint blockers (ICBs) can lead to favorable results by reinvigorating the anti-tumor immune response in some patients, many other patients experience poor prognosis and even tumor overgrowth can be seen in real practice. We aimed to assess these hyperprogressive disease (HPD). Methods We reviewed NSCLC patients (n = 243) treated with ICBs. HPD was defined as a tumor growth kinetic ratio (TGKr)>2 and a time-to-failure of less than 2 months. We analyzed the association of Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and CRP-albumin ratio (CAR) with HPD and the immune compositional change in TME by multiplex IHC(mIHC). Panel 1/2 showed CD4, CD8, FOXP3, CD45RO as T cell markers and CD3, TIM3, LAG3, PD-L1 as co-inhibitory signal markers. Panel 3/4 examined macrophages and NK cells with CD68, CD14, CD163, CD206, CCR7, CD86, CD103, CD56, CD11c and CD16. Results Overall, 231 patients were evaluated. 25 patients (10.8%) met the HPD. Patients with HPD (median, 5.6 mo; P Conclusions Despite improved recognition of HPD, its etiology remains unclear, but it is clear that the prognosis becomes poor when it occurs. We observed that some serologic biomarkers (NLR, PLR, CAR) and mIHC can be used not only to predict HPD, but also to validate its mechanism. Furthermore, we undergo whole exon sequencing and experiment with murine model to understand mechanism of HPD. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background Signet ring cell carcinoma (SRCC), a subtype of gastric cancer (GC), has specific epidemiology and oncogenesis, and has poor prognosis; it still has the highest number of unmet medical needs. Cytoskeletal rearrangement and disruption of cell integrity play crucial roles in SRCC pathogenesis. Recently, many studies have been conducted on molecular alterations in SRCC; with the clarification of the clinical significance of the CLDN-ARHGAP fusion gene, a large clinical trial is underway. Herein, we examined the influence of CLDN, RhoGAP, and E-cadherin on SRCC prognosis. Methods We reviewed advanced 663 GC patients who received palliative chemotherapy. Of these, 135 patients (20.4%) were SRCC. Multiplexed immunofluorescence was performed on the tissue samples using antibodies against CLDN18, RhoGAP, and E-cadherin. Positivty was defined as the median value of H-score. Results Overall, 85 (63%) of 135 SRCC patients, were analysed based on tissue availability. Median age at GC diagnosis was 52.5 (range 20-77) years; the female-to-male ratio was 1.2. CLDN 18 showed a strong positive correlation with E-cadherin (r = 0.705, P Conclusions The correlations among CLDN18, RhoGAP, and E-cadherin may be associated with the discohesive oncogenesis seen in SRCC. We propose that these discohesive factors may be associated with prognosis of metastatic SRCC. Further functional studies are needed to clarify the role of these molecules. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background Although definitive concurrent chemoradiotherapy (CRT) is considered standard of care for most of stage III NSCLC patients, neoadjuvant treatment followed by surgery can be considered for some potentially resectable patients. Rationales for neoadjuvant treatment are tumor regression effect before surgery, early eradication of micrometastasis and better tolerability of chemotherapy than in the post-surgical setting. Regarding potential benefits of combining PD-1 blockade with CRT, here we have an ongoing phase Ib trial which assesses the safety and feasibility of the combination of neoadjuvant CRT with durvalumab in potentially resectable stage III NSCLC (NCT03694236). Trial design Eligible patients with histologically confirmed NSCLC (potentially resectable clinical stage III according to the American Joint Committee on Cancer 8th staging system) are enrolled. Patients receive CRT (weekly paclitaxel 45 mg/m2 and carboplatin AUC 2 with radiotherapy of 45 Gy in 25 fractions) and durvalumab (Day 1 and 29, 1500mg) during 5 weeks followed by surgery. After surgery, patients are treated with durvalumab for one year (every 4weeks, 1500 mg). The primary endpoints are safety and tolerability. The secondary endpoints are objective response rate (ORR), R0 resection rate, disease-free survival (DFS), overall survival (OS), clinical or pathological downstaging rate and, pathologic complete response (pCR) rate in the primary tumor. Immune marker analysis by FACS, exome sequencing and RNA sequencing using cancer tissue of pre-treatment, after surgery, and after recurrence will be performed. Table . 1477TiP Steps of trial No. of patients Considerations Neoadjuvant (weekly paclitaxel 45 mg/m2 and carboplatin AUC 2, radiotherapy 45 Gy in 25 fractions, durvalumab day 1 and 29, 1500mg) Stage 1 1 9 1) If patients of ≥ 5 has grade≥3 TRAE the trial holds 2) If patients of ≤ 4 has grade≥3 TRAE the trial proceeds to the 2nd stage. Stage 2 21 If patients of ≤ 13(43%) has grade≥3 TRAE during the neoadjuvant treatment it will be considered tolerable and further analysis will be performed. 2 Surgery The time and modality of surgery will depend on the surgeon’s discretion. The maximum allowed interval between the end of neoadjuvant therapy and surgery is 9 weeks. If disease progresses during or after the neoadjuvant therapy, or if the surgeon thinks that the surgery is not feasible, concurrent chemoradiation or chemotherapy alone can be continued. Adjuvant (durvalumab 1500mg for one year every 4 weeks, total of 13 times.) The maximum allowed interval between the surgery and adjuvant therapy is 12 weeks. Follow up Response evaluation will be done until 5 years after the surgery. 3 (Chest CT every 3 months, Abdominal pelvic CT at 1, 2, 5 years after the surgery) 1 Additional enrollment will be hold until the first 9 patients proceeds surgery. 2 Grade≥3 TRAE during neoadjuvant chemoradiotherapy is expected to be 30∼50% according to the previous data. 3 Assessed according to the Response Evaluation Criteria in Solid Tumors(RECIST), version 1.1. TRAE; treatment-related adverse event, CT; Computed tomography. Clinical trial identification NCT03694236. Legal entity responsible for the study The authors. Funding AstraZeneca. Disclosure All authors have declared no conflicts of interest.

Background In patients with fine needle aspiration (FNA)-proven axillary lymph node metastasis at diagnosis (cN+), the current standard surgical procedure is axillary lymph node dissection (ALND) at definitive surgery after neoadjuvant chemotherapy (NAC). However, growing evidences suggest that SLNB after NAC is feasible and may demonstrate acceptable performance in selected patients. We performed sentinel lymph node biopsy in patients treated with cytologically-confirmed axillary lymph nodes metastases at presentation, who converted to a clinically negative axillary status after NAC (ycN0). Patients and methods We retrospectively evaluated 240 patients with invasive breast cancer with ultrasound-guided FNA-proven axillary nodal metastases at the time of diagnosis. All patients received NAC and underwent surgery at Samsung medical center between October 2007 and May 2013. Among these patients, 75 patients underwent SLNB. These patients converted to clinically node-negative disease (ycN0) after NAC on breast MRI or PET/CT scan. A combined detection technique was used with radioisotope and blue dye for the detection of SLN. Patients with negative SLN on frozen pathology and low clinical suspicion of metastasis during operation were not performed further ALND. Results The detection rate of SLNB was 93.3% (70/75), and median number of retrieved sentinel lymph nodes was 3.0 (range 1-8). False negative rate was 6.7% (1/15). Of these 75 patients, 35 (46.6%) patients had positive sentinel lymph nodes (ypN+) and underwent ALND. Thirty-five (46.6%) patients had tumor-free sentinel lymph nodes (ypN0sn) and 20 patients of them were followed without subsequent ALND. In these SLN-negative patients without further ALND, 9 patients were HER2-enriched subtypes and 9 patients, TNBC subtypes. Only two of them were Luminal B subtypes. The median follow-up period was 12.0 months (range 0-26 months) with 2 events; 1 regional recurrence in ipsilateral supraclavicular node and 1 systemic recurrence in brain on postoperative 7 months and 5 months, respectively. There has not occurred an ipsilateral axillary recurrence so far. Conclusions Although the follow-up was not long enough to conclude, this study tried to demonstrate that SLNB after NAC was feasible and further ALND may not be necessary in patients with SLN-negative disease (ypN0sn). Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-18-04.

Background: Imaging methods that use ionizing radiation in emergency departments (EDs) have increased with advances in radiological diagnostic methods. Physician and nurse awareness of the radiation dose in the ED and the associated cancer risks to which the patients are exposed were surveyed with a questionnaire.Methods: A total of 191 subjects in six EDs participated in this study. ED physicians and ED nurses were asked about the risks and the radiation doses of imaging methods ordered in the ED. The differences between the two groups were compared using Student’s t‑test for continuous variables. A Fisher’s exact and Chi‑squared tests were used for categorical variables.Results: A total of 82 ED physicians and 109 ED nurses completed the questionnaire; 38 (46.3%) physicians and 8 (7.3%) nurses correctly answered the question about the chest X‑ray radiation dose. A question about the number of chest X‑rays that is equivalent to the dose of a pelvic X‑ray was answered correctly by 5 (6.1%) physicians and 9 (8.3%) nurses (P = 0.571). Questions regarding abdominal computed tomography (CT), chest CT, brain CT, abdominal ultrasonography, and brain magnetic resonance imaging were answered correctly more frequently by the physician group than the nurse group (P < 0.05). The risk of developing cancer over a lifetime due to a brain CT was correctly answered by 21 (25.6%) physicians and 30 (27.5%) nurses (P = 0.170). A similar question regarding abdominal CT was correctly answered by 21 (25.6%) physicians and 42 (38.5%) nurses (P = 0.127).Conclusions: Knowledge of the radiation exposure of radiology examinations was lower in nurses than physicians, but knowledge was poor in both groups. ED physicians and nurses should be educated about radiation exposure and cancer risks associated with various diagnostic radiological methods.Keywords: Diagnostic imaging, emergencies, radiation dosage

Introduction: Circulating tumor DNA (ctDNA) is a new biomarker which could guide further treatment. Characterization of tumor mutation profiles is required for informed choice of therapy, given that biological agents target specific pathways and effectiveness may be modulated by specific mutations. It would have clinical utility for neoadjuvant setting also. Thus, we assess the potency of ctDNA to predict tumor response to neoadjuvant chemotherapy(NAC) in locally advanced breast cancer(LABC). Methods: We performed targeted deep sequencing of 30 plasma DNAs and 10 matched germline DNAs from 10 LABC patients. Serial plasma DNAs were collected at diagnosis, after 1st NAC and curative surgery. For the target enrichment, we designed RNA baits covering a total of ~202kb regions of human genome including a total of 83 cancer-related genes. We constructed the sequencing libraries according to the optimized protocol that we recently reported and sequenced on Illumina HiSeq2500 aiming a mean sequencing depth of ~10,000. After excluding unmapped reads, PCR duplicates and off-target reads, the coverage depths for plasma DNA and germline DNA samples were 2,627x and 4,833x on average, respectively. NAC response was measured by residual cancer burden(RCB) score, calculated as a continuous index combining pathologic measurements of primary tumor and nodal metastases for prediction of distant relapse-free survival. Results: We analyzed ctDNA and primary tumor tissues from 10 patients with LABC scheduled NAC followed by operation in Samsung Medical Center. Of ten LABCs, one excluded from analysis because of angiosarcoma of breast. Five samples were triple-negative breast cancers (BCs), 2 were HER2 positive BCs and others were ER positive BCs. In tumor response, 1 patient had pathologic complete response (pCR), 1 had RCB class I, 4 and 3 patients did RCB class II and III. Of 83 genes, in analysis of ctDNA at BC diagnosis, we found 2 to 6 mutations in each samples and 3 mutations were detected averagely. Most common mutation was TP53 (6 patients), followed by PIK3CA mutation. By measuring these mutations in serial ctDNA, we found that ctDNA had disappeared after first cycle of NAC in patient with pCR. In two patients with RCB class I, ctDNA had decreased by more than 10 percent (the level of ctDNA(pg/ml): 455.9 to 30.4, 5.8 to 0.0) of primary plasma sample after first NAC. Two patients increased level of ctDNA had tumor response with RCB class III and one patient had distant tumor recurrence within 3 months after curative surgery. However, correlation between the level of ctDNA and initial stage was not observed. Patient No.Initial stageSurgical stageRCB scoreRCB classct DNA at diagnosis (pg/5ml)ctDNA after 1st NAG (pg/5ml)Tumor recurrence12A11.3331455.930.4No22B00pCR446.60.0No33B2A1.31515.80.0No42A12.132246.255.4No52B11.7972107.811.6No63B3A4.09033401.15075.5Yes73A2B3.92235088.68536.7No Conclusions: This preliminary result suggests that serial monitoring of ctDNA would be a potiential surrogate marker to predict tumor response and recurrence during NAC in LABC patients. Further results with long-term outcomes are warranted. Citation Format: Kim J-Y, Park D, Jung HH, Bae SY, Yu JH, Lee SK, Kim SW, Lee JE, Nam SJ, Ahn JS, Im Y-H, Park YH. Clinical utility of serial monitoring of circulating tumor DNA (ctDNA)in patients with neoadjuvant chemotherapy (NAC) for locally advanced breast cancer (LABC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-02-11.

In this study, we analyzed a bacterial community closely associated with Cochlodinium polykrikoides that caused harmful algal blooming in the sea. Filtration using a plankton mesh and percoll gradient centrifugation were performed to eliminate free-living bacteria. Attached bacteria were analyzed by culture-dependent and culture-independent methods. Five culturable bacterial strains were isolated and identified from the C. polykrikoides mixed bacterial community. The isolates belonged to α-Proteobacteria (Nautella sp., Sagittula sp., and Thalassobius sp.) and γ-Proteobacteria (Alteromonas sp. and Pseudoalteromonas sp.). All of the 5 isolates showed algicidal activity against C. polykrikoides and produced extracellular compounds responsible for algicidal properties after entering the stationary phase. The algicidal compounds produced by the 5 isolates were heat-stable and had molecular masses of less than 10,000 Da. Furthermore, the algicidal compounds were relatively specific for C. polykrikoides in terms of their algicidal activities. Culture-independent analysis of the bacterial community in association with C. polykrikoides was performed using polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE). On the basis of the PCR-DGGE profile, Sagittula sp. was identified as a dominant species in the bacterial community of C. polykrikoides.

In current design practice, the shear wave velocity (Vs) of the core and rock-fill zone of a dam, one of the characteristics essential for seismic response design, is seldom determined by field tests. This is because the borehole seismic method is often restricted in application, due to stabilisation activities and concern for the security of the dam structure, and surface wave methods are limited by unfavourable in-situ site conditions. Consequently, seismic response design for a dam may be performed using Vs values that are assumed, or empirically determined. To estimate Vs for the core and rock-fill zone, and to find a reliable method for measuring Vs, seismic surface wave methods have been applied on the crest and sloping surface of the existing ‘M’ dam. Numerical analysis was also performed to verify the applicability of the surface wave method to a rock-fill dam. Through this numerical analysis and comparison with other test results, the applicability of the surface wave method to rock-fill dams was verified.

The reported frequencies of Gs alpha mutations (gsp mutations) in growth hormone (GH)-secreting pituitary adenomas are variable (ranging from 4.4 to 43%), and the presence of these mutations in the other pituitary adenomas is still a matter of controversy. Previous clinical and biochemical analyses of patients with GH-secreting pituitary adenomas and gsp mutations produced conflicting results and did not demonstrate obvious characteristics. Therefore, we investigated the prevalence of gsp mutations in Korean patients with pituitary adenomas and elucidated the characteristics of these patients. Forty-four GH-secreting adenomas, 7 prolactin (PRL)-secreting adenomas and 32 clinically non-functioning adenomas were examined for the presence of point mutations in codon 201 and 227 of the Gs alpha gene using a nested PCR and direct sequencing of DNA extracted from fresh tissue or paraffin-embedded pituitary adenoma samples. Seven of the 44 GH-secreting pituitary adenomas had point mutations at codon 201 or 227; of these, five mutations were in codon 201 and two were in codon 227. In patients with gsp mutations, mean tumor size was significantly smaller than in patients without gsp mutations (15.9+/-8.7 mm vs. 24.9+/-14.9 mm, P

Purpose The endovascular coiling of cerebral aneurysm is fundamentally based on exact evaluation of aneurysm size, shape and so-called working angle of procedure. Nowadays, as initial surveillance procedures, CT angiography has been performed prior to endovascular coiling of ruptured aneurysms. We retrospectively compared the initial CT angiography and initial working angle angiography focusing to interval changes, chosen treatment modality and its results. Material and methods One hundred twenty two patients, each with ruptured cerebral aneurysm(s), underwent endovascular coiling procedure between 2012 Jan and 2014 Nov. Immediately after recognition of subarachnoid hemorrhage (SAH) symptom or mental change, CT angiography was checked as initial diagnostic procedure. After confirmation of SAH, catheter angiography was performed for decision making. We compared the CT angiography and catheter angiography and subgrouping was performed same as follows; Group 1 = no changes, group 2 = smaller aneurysm at catheter angiography, group 3 = larger aneurysm at catheter angiography. Results The mean age was 53.9 years and female patients were dominant (80 cases). The mean interval of getting first image between CT angiography and catheter angiography was 115 minutes. Group 1 was 107 cases (87.7%). Group 2 was 11 cases (9.0%). Group 3 was 4 cases (3.3%). In group 2, the specific aneurysm location did not exist. Rather, “narrow neck with saccular dome” pattern was dominant (6 cases; 54.5% of group 2). The coiling procedures were successful in 9 cases (81.8%) in group 2, and one case of failed coiling showed typical discrepancy between CT angiography and catheter angiography. In group 3, specific aneurysm location could be found definitely; the dorsal wall of internal carotid artery was dominant (3 cases; 75% of group 3). In both groups, coiling procedures could be performed effectively based on working angle angiography as well as CT angiography. Conclusion The discordance between CT angiography and catheter angiography was infrequent, but in these cases, mutual supplement is critical for exact decision making and safe endovascular coiling procedure. The CT angiography should be performed with same importance of working angle angiography. Disclosures J. Sung: None. D. Lee: None. S. Kim: None. H. Lee: None. S. Lee: None.

Objectives:Haemangiomas do not develop as commonly in the sinonasal cavity, compared with other head and neck sites. The clinical characteristics of sinonasal cavity haemangiomas and the results for endoscopic resection have been addressed in the literature only briefly. Thus, this study aimed to evaluate these points.Materials and methods:A retrospective chart review was undertaken of 22 patients who had undergone endoscopic excision of sinonasal cavity haemangiomas, in order to define clinical characteristics and tumour control rates.Results and analysis:The most common presenting symptom was epistaxis. The most prevalent site was the inferior turbinate (45.5 per cent), followed by the maxillary sinus (18.2 per cent). No recurrence was observed in any patient.Conclusion:Although past studies have described external approach sinonasal surgery as the mainstay of treatment, our results imply that endoscopic excision of sinonasal haemangiomas yields excellent outcomes in terms of tumour control and safety.