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Background: Robot nipple sparing mastectomy (RNSM) has emerged for breast cancer treatment and for risk reducing mastectomy in women who have high risk of pathogenic variants. Even though several studies have reported that RNSM is a feasible procedure, some argue that RNSM are only performed by several specialized surgeons and there is only limited data reporting about the oncologic outcome and patient reported outcome (PRO). Recently, the United States Food and Drug Administration and several surgeons have warned that robot breast surgery should be performed only by specialized surgeons and the benefits, risks, and alternatives of all available treatment options should be discussed with patients to make the most informed treatment decision. The Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) has been established to evaluate, standardize, and developing education program this cutting-edge procedure. We designed a multicenter prospective cohort study of Mastectomy with Reconstruction including Robot Endoscopic Surgery (MARRES) to report surgical outcome, PRO, and oncologic outcome. Methods: The MARRES study is a multi-institution cohort study that prospectively collects data from patients undergoing mastectomy and reconstruction. Patients' inclusion criteria are as below; adult women over the age of 19, with breast cancer or high risk of breast cancer (patients with a BRCA1/2 mutation, TP53 mutation, and PALB2 mutation), who scheduled therapeutic or prophylactic mastectomy, and who want immediate reconstruction. Surgical outcomes, oncologic outcomes, cost-effectiveness, and PRO were collected. The primary endpoints were postoperative complication rates in postoperative 30 days and Clavien-Dindo grade of postoperative complications in postoperative 180 days. The secondary endpoints were recurrence free survival in postoperative 5 years, cancer incidence rate in postoperative 5 years for those who underwent risk reducing mastectomy, patient's satisfaction within preoperative 4 weeks and results within postoperative 6 months to 12 months, surgeon's satisfaction about the postoperative results in postoperative 6 months, and cost-effectiveness of the definitive surgery. Patient recruitment will be finished in April 2025 and the goal number of enrolled patients is 2,000. Discussion: This study will provide evidence of the surgical outcome, PRO, and oncologic outcome of RNSM and endoscopic NSM compared to conventional NSM. Trial registration: ClinicalTrials.gov Identifier NCT04585074. Registered April 8, 2020. Citation Format: Jeea Lee, Jai Min Ryu, Jee Yeon Lee, Beom Seok Ko, Saebyeol Lee, Joo Heung Kim, Hee Jun Choi, Hyuk-Jae Shin, Young Woo Chang, Hye Yoon Lee, Hong-Kyu Kim, Hyung Seok Park. Mastectomy with reconstruction including robot endoscopic surgery (MARRES): A prospective cohort study of the Korea robot-endoscopy minimal access breast surgery study group (KoREa-BSG) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-12-01.

The ranked discrepancy model (RDM) is a relatively novel needs assessment approach and is optimized for addressing ordinal and non-normally distributed data. This study aimed to explore the viability of the RDM by comparing the results obtained from it with those obtained using two other long-standing needs assessment models, and to prioritize the learning needs of secondary school career guidance teachers in South Korea using the RDM as an initial effort to improve the pre-service and in-service educational programs of teachers. Data were collected from 75 career guidance teachers by using a survey questionnaire. The results from the RDM, the weighted total index (WTI) approach, and the Borich model demonstrated a great deal of consistency in terms of the rankings of career guidance teachers’ learning needs. This implies that the RDM is a useful quantitative method for needs assessment in cases involving ordinal items, cross-sectional data, or non-normally distributed data. This study also revealed that “providing and utilizing occupational information” is the biggest shortfall among the job tasks required of secondary school career guidance teachers, compared to its importance. Uncertainty about the future might make it more difficult for career guidance teachers to provide students with the appropriate occupational guidance.

At a time of global economic crisis, professional programs in universities are demanded to make continuous improvements based on new information on performance gaps of novice incumbents, in order to make their graduates more competitive, which ultimately leads to their job security and decent work. Accordingly, this study aimed to assess discrepancies in the importance and performance levels of professional capabilities required of novice Human Resource Development (HRD) practitioners and priorities in instructional needs, as perceived by immediate superiors as an initial effort to improve the curricula of undergraduate HRD courses. Data were collected from 193 HRD supervisors in organizations in South Korea and were analyzed using paired t-test and the ranked discrepancy model. These findings indicated that instructional needs in terms of professional capabilities were high in the following order: instructional design, learning science, career and leadership development, coaching, training delivery and facilitation, knowledge management, and technology application. The results implied that most undergraduate courses developed for the education of prospective HRD practitioners need to be updated and improved. This study also proposed an idiosyncratic and periodic formative evaluation process for the ongoing improvement of professional programs in universities as a part of efforts to sustain the global economic growth.

BACKGROUND/AIM In the present study, the breast cancer patient-derived orthotopic xenograft (PDOX) model was used to identify an effective drug for a highly aggressive triple negative breast cancer (TNBC). MATERIALS AND METHODS The TNBC tumor from a patient was implanted in the right 4th inguinal mammary fat pad of nude mice to establish a PDOX model. Three weeks later, 19 mice were randomized into the untreated-control group (n=10) and the eribulin treatment group (n=9, eribulin, 0.3 mg/kg, i.p., day 1). RESULTS On day 8, eribulin significantly inhibited tumor volume compared to the control group (p

Introduction: Patients with Hormone receptor (HR)-positive / HER2-negtive breast cancer have not received targeted therapy for Her2 based on criteria of the protein expression or DNA copy number amplification. However, the clinical meaning of the level of Her2 signaling activity has not been fully elucidated yet. We recently developed a novel technique of single-molecule protein-protein interaction (PPI) profiling to investigate the importance of HER2 signaling activity in this major subgroup of breast cancer. Methods: This study is a study with the biospecimen and registered medical record from the prospective collected cohort of Samsung Medical Center, and all of these biospecimens were provided by Samsung Medical Center BioBank. First, We selected 138 of 8463 patients who were diagnosed with invasive breast cancer by curative surgery between January 2008 and December 2013. Specimens were selected based on modified Allred Immunohistochemistry (IHC) scores; 6 for hormone receptors (ER/PR+) and 1 for Her2. Then, we applied the single-molecule co-immunoprecipitation, a novel technology determining protein-protein interactions (PPIs), to each selected biospecimen. PPI and expression level for HER2 protein of each tumor extract were analyzed with HER2-PPI-Dx kit. All the measurement were performed using a single-molecule fluorescence imaging equipment. Based on HER2 PPI and expression level analysis, we developed an algorithm based on the 72 patients’ samples which can predict the prognosis of these patients. This algorithm was validated with the samples from the other 66 patients. Results: In total, 138 samples from each patients (72 in training set and 66 in validation set) were analyzed. The median follow-up time was 68.0 (range: 7-123) months. Single-molecule measurement for HER2 level showed that clinical specimens showed significant differences in HER2-PPI level even though they had the same IHC score (65-fold from 117 patients with ‘HER2 IHC score: 0’ and 33-fold from 21 patients with ‘HER2-IHC score: 1’, respectively). For the training set, by combining HER2 PPI and HER2 protein expression data, we could select 12 patients (17%) as a high level HER2-PPI group. This high level HER2-PPI group showed the significantly poorer disease free survival (DFS) rate compared to that of the low level group (42% for high-level vs. 83% for low-level, p=0.001). For the validation set with the same cutoff, 17 patients (26%) with identified as high level HER2-PPI group. We still found a significantly poorer DFS rate in this group compared to that of the low level group (82% vs. 88%, p=0.033). For total 138 patients set, we found a significantly poorer DFS rate in this group compared to that of the low level group (p=0.014). Conclusion: Our results showed that HER2 PPI may have an important clinical meaning to identify a high risk of recurrence in the patients with strong HR-positive and HER2-negative breast cancers defined by conventional method. For those patients with high level HER2-PPI, HER2-targeted therapies may be beneficial despite of their HER2-negativity. This will be proved for the future. Citation Format: Hee Jun Choi, Hong Won Lee, Sangmin Kim, Tae-Young Yoon, Hyunwoo Kim, Seul Lee, Seok Jin Nam, Seok Won Kim, Sooyoun Cho, Yeon Hee Park, Jeong Eon Lee. Protein-protein interaction of HER2 predicts the prognosis of hormone receptor-positive HER2-negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-26.

Introduction: The aim of this study was to evaluate the prognostic value of the number of lymph nodes removed in breast cancer patients who undergo axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC). Methods: We included patients who were diagnosed with invasive breast cancer and cytology with proven involved axillary node metastasis at diagnosis and treated with NAC followed by curative surgery at Samsung Medical Center between January 2007 and December 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Results: Among 772 patients with NAC and ALND, there were 285 ypN0, 258 ypN1, 135 ypN2, and 94 ypN3 cases. The median follow-up duration was 69.0 months. The group with less than 10 lymph nodes number (

The purpose of this study was to evaluate pathologic lymph node metastasis in breast cancer with cytology-proven axillary metastasis. This study was designed prospectively. We performed axillary lymph node dissections (ALND) after lymphatic mapping by near-infrared (NIR) fluorescence imaging with Indocyanine Green (ICG). We evaluated 72 breast cancer patients with cytology-proven axillary metastasis by curative surgery at the Samsung Medical Center between May of 2016 and December of 2017. Among the 72 patients with cytology-proven axillary metastasis, 14 of 39 patients (35.9%) with one or two sentinel lymph nodes containing metastases were metastasized to post-sentinel lymph node. Thirteen of fourteen patients had additional non-sentinel lymph node metastases, seven of thirteen patients also had additional level II lymph node metastases, and one patient had only one additional level II lymph node metastasis. Of T1 or T2 stage patients, 10 of 33 patients (30.3%) with one or two sentinel lymph nodes containing metastases were metastasized to post-sentinel lymph node. Even in patients without SLN metastasis, 50% of the patients had at least three LN metastases, and 40% in the T1 or T2 stage patients. Sentinel lymph node biopsy without ALND might be not safe for patients with cytology-proven axillary metastasis.

This study aimed to empirically examine the factors affecting full-time undergraduate students’ satisfaction and academic performance measured by grades using an existing large administrative dataset. The sample consisted of 21,662 undergraduate students who took online liberal arts courses offered by a large traditional Korean university in the spring semester of 2020. The theoretical framework of this study was formulated by selectively adopting and slightly modifying some of the factors from Choi’s conceptual model for adult dropout from online degree programs. The findings indicated that gender, previous GPA, campus, type of online course, the relevance of the course, adequacy of assignments and assessments, learner-instructor interaction, and learner-content interaction significantly affect students’ degree of satisfaction with online liberal arts courses. This study also found that students who considered the course less relevant to their goals or interests, had a low previous GPA, had frequent learner-instructor interactions, few learner-content interactions, and a low level of course satisfaction are more likely to earn a grade of B, C, or lower than to receive an A in online liberal arts courses.

Purpose Restricted shoulder motion is a major morbidity associated with a lower quality of life and disability after axillary lymph node dissection (ALND) in patients with breast cancer. This study sought to evaluate the antiadhesive effect of a poloxamer-based thermosensitive sol-gel (PTAS) agent after ALND. Methods We designed a double-blind, multicenter randomized controlled study to evaluate the clinical efficacy and safety of PTAS in reducing upper-limb dysfunction after ALND. The primary outcome was the change in the range of motion (ROM) of the shoulder before surgery and 4 weeks after ALND (early postoperative period). Secondary outcomes were shoulder ROM at six months, axillary web syndrome, and lymphedema (late postoperative period). Results A total of 170 patients with planned ALND were randomly assigned to one of 2 groups (poloxamer and control) and 15 patients were excluded. In the poloxamer group (n = 76), PTAS was applied to the surface of the operative field after ALND. ALND was performed without the use of poloxamer in the control group (n = 79). Relative to the control group, the poloxamer group had significantly lower early postoperative restrictions in total shoulder ROM at four weeks (-30.04 ± 27.76 vs. -42.59 ± 36.79; p = 0.0236). In particular, the poloxamer group showed greater reductions in horizontal abduction at four weeks (-3.92 ± 9.80 vs. -10.25 ± 15.42; p = 0.0050). The ROM of the shoulder at 24 weeks, axillary web syndrome, and lymphedema were not significantly different between the two groups. No adverse effects were observed in either group. Conclusion We suggest that poloxamer might improve the early postoperative shoulder ROM in patients with breast cancer who have undergone ALND. Trial registration ClinicalTrials.gov Identifier: NCT02967146.

Numerous studies have shown that vitamins reduce the risk of cancers, but the relationship between serum vitamin levels and breast cancer is still controversial. In this study, we evaluated serum levels of vitamins in Korean patients with benign breast disease or breast cancer and investigated their associations with clinical and laboratory parameters. Concentrations of vitamin A, D, and E, together with homocysteine and methylmalonic acid as biomarkers of vitamin B12 deficiency, were measured by high-performance liquid chromatography (HPLC) or liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the serum of 104 breast cancer patients, 62 benign breast disease patients, and 75 healthy Korean females. We further assessed possible associations between vitamin levels and breast cancer subtypes, the presence of lymph node metastasis, and tumor stages. Serum concentrations of vitamins A and E were significantly lower in breast cancer patients and in benign breast disease patients than in healthy controls. Severe vitamin D deficiency was more prevalent in breast cancer patients than in healthy controls. Vitamin D level was significantly lower in breast cancer patients with estrogen receptor-negative or triple-negative subtypes than in those with other subtypes. Further research with a larger study population is required to elucidate the role of vitamins in breast cancer.

Background/Aim: The aim of this study was to establish a patient-derived orthotopic xenograft (PDOX) mouse model of liver metastasis of triple-negative breast cancer (TNBC) and examine the efficacy of oral recombinant methioninase (o-rMETase) on the liver metastasis. Materials and Methods: TNBC from a patient was implanted in the left hepatic lobe of nude mice to simulate liver metastasis in a PDOX model. Ten days later, all mice underwent laparotomy to measure tumor size and were randomized to three groups: control; o-rMETase 100 U once daily (qd); and o-rMETase 200 U qd. After 9 days of treatment, all mice were sacrificed. Results: At the end of the treatment period for the liver metastasis, the size of liver metastases was 372.6 mm(3) in the control group; 160.0 mm(3) in the o-rMETase 100 U group; and 245.3 mm(3) in the o-rMETase 200 U group. All mice had ascites and 12 out of 14 mice in all groups had mesenteric lymph-node metastasis, as re-metastasis. The mean body-condition score was 1.5 in the control group; 2.4 in the o-rMETase 100 U group; and 2.6 in the o-rMETase 200 U group (control group vs. o-rMETase 200 U group, p

Backgrounds With increasing screening for breast cancer, non-palpable breast lesions are detected more frequently. A preoperative localization is very important for a minimal but accurate excision of a non-palpable breast lesion. The purpose of this study was to evaluate the efficacy and safety of indocyanine green(ICG)-hyaluronic acid mixture injection as a novel material for localization. Methods We performed prospective clinical trial with female patients who underwent surgery for non-palpable breast lesion. All patients were sequentially assigned to the control group(localization with activated charcoal), test group 1(ICG-hyaluronic acid mixture 0.1ml), or test group 2(ICG-hyaluronic acid mixture 0.2ml) by 1:1:1 ratio. Results A total of 44 patients were eligible for this study (control group = 14, test 1 group = 15, test 2 group = 15 patients ). Among all patients, Fibroadenoma accounted for the largest share (38.6%, 17/44) and malignancy accounted for 11.4% (5/44). There was no difference in baseline characteristics in three groups. The marking rate was over 86% in all groups, and there was no difference. However, skin pigmentation was only in the control group and the accuracy of resection (the greatest length in cm of the excised specimen divided by the greatest length in cm on the pre-operation ultrasound image, the value closer to 1 meant resection as much as the size on ultrasound image) was different significantly. The average was 3.7 in control group and 2.2 in test 1 group and 2.1 in test 2 group. ( p-value was 0.037 between control and test 1 group, 0.744 between test 1 and test 2 group, 0.026 between control and test2 group respectively. ) Conclusion ICG-hyaluronic acid mixture injection is a new method for localization with non-palpable breast lesions, as well as a better method with higher accuracy of resection, lower skin pigmentation. Further research is required to apply this method to malignant breast lesions.Trial registration “A Multi-center Open-label Parallel Phase-2 Clinical trial to evaluate the efficacy and safety of LuminoMarkTM for Localization in Patients with Non-palpable Breast Lesions” was prospectively registered as a trial (ClinicalTrials. gov Identifier: NCT03743259, date of registration: May 29, 2018, https://clinicaltrials.gov/ct2/show/NCT03743259).

Background/Aim: The aim of the study was to use a triple-negative breast cancer (TNBC) patient-derived orthotopic xenograft (PDOX) model to examine the efficacy of oral recombinant methioninase (o-rMETase) against this recalcitrant disease. Materials and Methods: The TNBC tumor from a patient was implanted in the right 4(th) inguinal mammary fat pad of nude mice. Two weeks later, the mice underwent tumorectomy with grossly-negative surgical margins. Two days after tumorectomy the mice were divided in two groups: one control and one treated with o-rMETase. Results: Tumors recurred in all mice. On day 11, the mean recurrent tumor volumes were 936.7 mm(3) in the control group and 450.9 mm(3) in the o-rMETase group (p

A recent study conducted at the University of Tennessee Medical Center using a large dataset from the National Cancer Database (NCDB) reported the use of nomograms for predicting Oncotype DX™ (ODX) scores with clinicopathologic data. We reviewed the data of 218 patients who underwent the ODX test at a single institution in Korea to confirm that nomograms can accurately predict ODX score groups using our data, which differ from those of the NCDB in terms of ethnicity. The concordance index (c-index) of nomograms was much lower than that of the University of Tennessee Medical Center for high- and low-risk groups of commercial ODX and Trial Assigning Individualized Options for Treatment values. Although the nomogram for predicting ODX scores was based on a large dataset, it could not be generalized to patients in Asia. Further studies using large datasets of patients from different ethnicities should be performed to develop a nomogram applicable to patients worldwide.

Purpose The American Joint Committee on Cancer (AJCC) recently released the breast cancer staging system, 8th edition, which included additional four biologic factors. However, there has been no external validation of the prognostic value of the new stages with different population-based databases. Methods To validate the prognostic value of the new staging system in the Asian population, with a focus on Korean patients with breast cancer, we performed a retrospective study with data from the Korean Breast Cancer Society that included 24,014 patients with invasive ductal or lobular carcinoma who underwent surgery between January 2009 and January 2012 in Korea. The proportional differences were evaluated between the anatomic staging system (AJCC 7th edition) and the prognostic staging system (AJCC 8th edition, December 2017 published version). Comparisons of overall survival (OS) and disease-free survival (DFS) with Kaplan-Meier graphs and hazard ratios were also performed. Results Our analysis included 24,014 patients (median age, 50 years; range, 20-91 years). Stage I, II, and III disease accounted for 47.6%, 43.5%, and 8.9%, respectively, of anatomic stages and 61.8%, 27.6%, and 10.8%, respectively, of clinical prognostic stages. A total of 6,272 cases (26.1%) were upstaged, 4,656 (19.4%) were downstaged, and 13,086 (54.5%) remained unchanged. OS and DFS decreased in the order from prognostic stages IA to IIIC but did not change among the anatomic stage groups. Conclusion Our data suggests that the prognostic staging system provides superior prognostic value to the anatomic staging system in Korean patients with breast cancer.

We evaluated the relationship between breast pathologic complete response (BpCR) and axillary pathologic complete response (ApCR) after neoadjuvant chemotherapy (NACT) according to nodal burden at presentation. As the indications for NACT have expanded, clinicians have started clinical trials for the omission of surgery from the treatment plan in patients with excellent responses to NACT. However, the appropriate indications for axillary surgery omission after excellent NACT response remain unclear.Data were collected from patients in the Korean Breast Cancer Society Registry who underwent NACT followed by surgery between 2010 and 2020. We analyzed pathologic axillary nodal positivity after NACT according to BpCR stratified by tumor subtype in patients with cT1-3/N0-2 disease at diagnosis.A total of 6,597 patients were identified. Regarding cT stage, 528 (9.5%), 3,778 (67.8%), and 1,268 (22.7%) patients had cT1, cT2, and cT3 disease, respectively. Regarding cN stage, 1,539 (27.7%), 2,976 (53.6%), and 1,036 (18.7%) patients had cN0, cN1, and cN2 disease, respectively. BpCR occurred in 21.6% (n = 1,427) of patients, while ApCR and pathologic complete response (ypCR) occurred in 59.7% (n = 3,929) and ypCR 19.4% (n = 1,285) of patients, respectively. The distribution of biologic subtypes included 2,329 (39.3%) patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative disease, 1,122 (18.9%) with HR-positive/HER2-positive disease, 405 (6.8%) with HR-negative/HER2-positive disease, and 2,072 (35.0%) with triple-negative breast cancer . Among the patients with BpCR, 89.6% (1,122/1,252) had ApCR. Of those with cN0 disease, most (99.0%, 301/304) showed ApCR. Among patients with cN1-2 disease, 86.6% (821/948) had ApCR.BpCR was highly correlated with ApCR after NACT. In patients with cN0 and BpCR, the risk of missing axillary nodal metastasis was low after NACT. Further research on axillary surgery omission in patients with cN0 disease is needed.

Background: Protein-protein interactions (PPIs) modulate the vast majority of cellular processes. Therefore, profiling PPIs occurred in a clinical specimen may facilitate to understand molecular mechanisms involved in disease progression such as cancer. In breast cancer diagnosis, molecular subtyping is an important step for decision-making clinically. However, the molecular subtype is determined simply according to the expression level of receptors (hormone receptors and HER2). Here, we present the use of single-molecule analysis to visualize PPIs in a clinical specimen. We further assess the potential use of PPI-profiling to screen a subgroup of breast cancer patients who show aberrant PPIs. Methods: In total, 138 fresh-frozen breast tumor tissues were profiled. Specimens were selected based on IHC scores with an average follow-up of 7.5 years; ≥ 7 for hormone receptors (ER/PR+) and ≤ 1 for HER2 (HER2-) determined by IHC-scoring guidelines. We analyzed expression levels and strengths of PPIs for HER2, HER3 and EGFR from breast cancer specimens by applying single-molecule pull-down and co-immunoprecipitation techniques - a novel technology based on single-molecule fluorescence imaging (Proteina co., Ltd.). Tumor proteins were extracted from fresh-frozen tumor tissue via cryogenic grinding followed by the addition of tissue lysis buffer. Single-molecule PPI and expression level analysis were performed by using EGFR-PPI-Dx kit and proto-type HER2/HER3-PPI-Dx kit, respectively. Single-molecule analysis for the prepared kit was carried out using ProViewTM, an automated single-molecule fluorescence imaging equipment. Disease-free survival between groups were compared using Kaplan-Meier survival curve analysis and log-rank test was performed to determine the difference of survival distributions between groups. Results: 72 (discovery set) and 66 (validation set) patients were analyzed, respectively. Single-molecule measurement for HER2 level demonstrated that clinical specimens showed significant differences in HER2 level even though they had the same IHC score (up to 65-fold from 117 patients with ‘IHC-0’ and 33-fold from 21 patients with ‘IHC 1’, respectively). By combining HER2 PPI and expression data, we screened 12 patients (17%) as a high HER2-signal group, which showed positive HER2-PPI and enhanced HER2-level from a discovery set. Interestingly, this high HER2-signal group showed the enhanced tumor recurrence rate compared to that of low HER2-signal (58% for high HER2-signal vs. 17% for low HER2-signal, log-rank p=0.001). Using the same cutoff, we screened 17 patients from validation set and this screened group showed higher tumor recurrence risk rate than the low HER2-signal/group-prevalence (18% vs. 12%/13.6%, log-rank p=0.033). Conclusions: Defining a cancer patient by individual molecular features is a cornerstone of precision medicine. A comprehensive understanding of the molecular landscape may help a physician deciding a biomarker-driven treatment patient-by-patient. Molecular profiling (PPI and expression level) at single-molecule level enables to determine the strength of PPIs and the quantity of proteins quantitatively and precisely. In this study, we describe a novel concept of patient-classification by single-molecule PPI analysis. Our PPI analysis reveals a subgroup of HR+/HER2- patients who show an enhanced HER2-initiated signaling, which was hidden by conventional techniques. We further identified that this subgroup exhibited higher recurrence rate than the prevalence of whole group we tested. Our findings propose that adjuvant HER2-targeted therapies along with hormone-therapy may be a new opportunity to patients screened by PPI profiling for reduced risk of tumor recurrence. Citation Format: Hong Won Lee, Hee Jun Choi, Hyunwoo Kim, Seul Lee, Sangmin Kim, Tae-Young Yoon, Jeong Eun Lee. Profiling protein-protein interactions at single-molecule level as a novel biomarker-driven screening method for the detection of tumor recurrence in breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-03-03.

Background/aims Despite effective therapeutic strategies for treating hormone receptor-positive (HR+) breast cancer, resistance to endocrine therapy that is either de novo or acquired still occurs. We investigated epidermal growth factor receptor (EGFR) as a therapeutic target for overcoming endocrine resistance in HR+ breast cancer models. Methods Using clinical data from 2,166 patients who had HR+ breast tumors and received tamoxifen, we analyzed survival rates. Levels of mRNA and protein expression were analyzed by real-time PCR and western blotting, respectively. Cell viability was analyzed by MTT assays and anchorage-independent growth by soft agar colony-formation assays. Efficacy of tamoxifen and/or gefitinib was analyzed using orthotopic xenograft mouse models. Results EGFR expression was significantly associated with more advanced stage and higher grade. EGFR expression was different in luminal A-like (Lum A, 1.3%) versus luminal B-like (Lum B, 11.4%) subtypes. On multivariate analyses for survival Lum B subtype EGFR+ tumors showed a hazard ratio (HR) of 5.22 (95% CI, 1.29-21.15, P = 0.020) for overall survival (OS) and HR of 2.91 (95% CI, 1.35-6.28, P = 0.006) for disease-free survival (DFS). Levels of EGFR inversely correlated with ER-α expression. Basal ER-α level was completely blocked by TGFA or EGF treatment. With TGFA pretreatment, ER+ breast cancer cells were resistant to 4-hydroxytamoxifen (4-OHT). Conversely, downregulation of ER-α by TGFA was reversed by gefitinib with recovered sensitivity to 4-OHT. Tumorigenicity of EGFR and ER+ breast cancer cells were significantly decreased by combined tamoxifen and gefitinib. Conclusion Aberrant EGFR expression was associated with poor prognosis in ER+ breast cancers, especially the Lum B subtype. Loss of ER by EGFR activation induced tamoxifen resistance. Therefore, EGFR could be a therapeutic target for overcoming recurrence of ER+ breast cancer with high EGFR expression.

Background/Aims: Despite effective therapeutic strategies for treating hormone receptor-positive (HR+) breast cancer, resistance to endocrine therapy that is either de novo or acquired still occurs. We investigated epidermal growth factor receptor (EGFR) as a therapeutic target for overcoming endocrine resistance in HR+ breast cancer models. Methods: Using clinical data from 2,166 patients who had HR+ breast tumors and received tamoxifen, we analyzed survival rates. Levels of mRNA and protein expression were analyzed by real-time PCR and western blotting, respectively. Cell viability was analyzed by MTT assays and anchorage-independent growth by soft agar colony-formation assays. Efficacy of tamoxifen and/or gefitinib was analyzed using orthotopic xenograft mouse models. Results: EGFR expression was significantly associated with more advanced stage and higher grade. EGFR expression was different in luminal A-like (Lum A, 1.3%) versus luminal B-like (Lum B, 11.4%) subtypes. On multivariate analyses for survival Lum B subtype EGFR+ tumors showed a hazard ratio (HR) of 5.22 (95% CI, 1.29-21.15, P = 0.020) for overall survival (OS) and HR of 2.91 (95% CI, 1.35-6.28, P = 0.006) for disease-free survival (DFS). Levels of EGFR inversely correlated with ER-α expression. Basal ER-α level was completely blocked by TGFA or EGF treatment. With TGFA pretreatment, ER+ breast cancer cells were resistant to 4-hydroxytamoxifen (4-OHT). Conversely, downregulation of ER-α by TGFA was reversed by gefitinib with recovered sensitivity to 4-OHT. Tumorigenicity of EGFR and ER+ breast cancer cells was significantly decreased by combined tamoxifen and gefitinib. Conclusion: Aberrant EGFR expression was associated with poor prognosis in ER+ breast cancers, especially the Lum B subtype. Loss of ER by EGFR activation induced tamoxifen resistance. Therefore, EGFR could be a therapeutic target for overcoming recurrence of ER+ breast cancer with high EGFR expression. Citation Format: Yisun Jeong, Soo Youn Bae, Daeun You, Seung Pil Jung, Hee Jun Choi, Isaac Kim, Se Kyung Lee, Jonghan Yu, Seok Won Kim, Jeong Eon Lee, Sangmin Kim, Seok Jin Nam. Epidermal growth factor receptor as therapeutic target in hormone receptor-positive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-04-25.

The relationships between serum levels of trace elements and breast cancer remain relatively unknown. In this study, we investigate serum levels of seven trace elements in Korean breast cancer patients compared to controls without breast cancer. Serum trace element levels were determined using inductively coupled plasma mass spectrometry in Korean breast cancer patients before initiation of breast cancer treatment. Korean females without breast cancer served as a control group. Trace element levels were measured in the discovery cohort (n = 287) and were validated in an independent cohort (n = 142). We further investigated possible associations between trace element levels and the presence of lymph node metastasis, distant metastasis, or triple-negative breast cancer among breast cancer patients in subgroup analyses. Serum manganese and molybdenum levels were significantly higher (p &lt, 0.05) in breast cancer patients than in controls. Serum copper levels were significantly higher in breast cancer patients with distant metastasis, while selenium levels were significantly lower. Other trace elements were neither significantly different between breast cancer patients and controls nor between subgroups of breast cancer patients. Our study provides insights about the potential roles and impacts of trace elements through an assessment of the associations between trace elements and breast cancer.

Purpose Many patients with cytology proven node-positive breast cancer receive a neoadjuvant chemotherapy (NAC) treatment. We developed a nomogram to predict the breast and axillary pathologic complete responses (pCR) in patients with a cytologically proven axillary node positive breast cancer with NAC. Methods We selected 995 patients who were diagnosed with an invasive breast cancer and axillary lymph nodes metastasis, and who were treated with NAC followed by a curative surgery at the Samsung Medical Center between January 2007 and December 2014. The baseline patient and tumor characteristics, chemotherapy regimen, and tumor and nodal responses were thoroughly analyzed and reviewed. A nomogram was developed using a binary logistic regression model with a cross validation. Results Axillary pCR was achieved in 47.3% and breast pCR was achieved in 24.3% of the patients after NAC. In this case, the both pCR was associated with an initial clinical tumor stage, negative progesterone receptor status, positive human epidermal growth factor receptor 2 status, and clinical radiologic nodal responses. A nomogram was developed based on the clinical and statistically significant predictors. It had good discrimination performance (area under the curve [AUC], 0.868; 95% confidence interval, 0.84-0.89) and calibration fit as noted in that case. The cross validation had an average AUC 0.853 (0.837-0.869). Conclusion Our nomogram might help to predict breast and axillary pCRs after NAC in patients with an initially node-positive breast cancer. Minimal surgery might be acceptable in patients for whom the nomogram indicates a high probability of achieving pCRs.

Purpose – The purpose of this paper is to examine the results of an empirical exploration of the relationship between learning transfer climates and organizational innovation. Additionally, factors associated with learning transfer climate that could account for innovation in Korean public and private organizations have been explored. Design/methodology/approach – This study relies on quantitative data obtained from two survey questionnaires. The sample consists of 390 employees working for seven private and five public organizations; further, each employee has completed at least one training program within a one-year period. Findings – Results of the study demonstrate that private, rather than public organizations, have significantly higher mean scores for all five learning transfer climate variables and for perceived organizational innovation. The results of multiple regression analyses reveal that openness to change and performance coaching have common and significant impacts on perceived innovation in both private and public organizations. However, the other three variables (i.e., transfer effort-performance expectations, performance-outcomes expectations, and performance self-efficacy) have varied effects on perceived innovation depending on organizational type. Specifically, transfer effort-performance expectations has a relatively meaningful impact on perceived innovation in public organizations. Performance-outcomes expectations and performance self-efficacy have relatively meaningful effects on perceived innovation in private organizations. Research limitations/implications – The sample for this study consists of employees solely from Korean organizations. Therefore, further studies encompassing a greater sampling variety are required to determine the generalizability of these results. In addition, this study is limited to an investigation of the possible differences between public and private organizations with respect to their learning transfer climates and innovation. In studies to follow, researchers can further investigate these relationships in segmented organizations. Originality/value – The results of this study will assist human resource practitioners to promote innovation effectively and efficiently based on organizational type.

PURPOSE This study aimed to evaluate the rate, patterns, and risk factors associated with tumor recurrence in patients with T1N0 gastric cancer. MATERIALS AND METHODS The medical records of 8,753 patients with pathological T1N0M0 gastric cancer who underwent gastrectomy between 1994 and 2014 at Sungkyunkwan University School of Medicine were examined. RESULTS Among the 8,753 patients, 95 patients (1.1%) experienced tumor recurrence; this included 31 remnant, 27 hematogenous, 9 lymph nodal, 5 peritoneal, and 23 multiple-site recurrences. When patients were divided into two groups according to the presence of tumor recurrence, the following characteristics were higher in the recurrence group than in the non-recurrence group: older age (≥65 years), male gender, undifferentiated histology, submucosal invasion, and venous invasion. In multivariate analysis, older age, male gender, tumor depth (sm2 and sm3 invasion), and venous invasion were independent risk factors for tumor recurrence. The recurrence rates were 0.7% in patients with less than two risk factors, 1.7% in those with two risk factors, 3.0% in those with three risk factors, and 6.3% in those with four risk factors (P

Purpose Although the indications for nipple-sparing mastectomy (NSM) are expanding, there remains a debate regarding the oncologic outcomes of patients treated with this method, especially those with a short tumor–nipple distance (STND). The aim of this study was to compare the long-term oncologic outcomes between patients with a long tumor–nipple distance (LTND) (≥ 2.0 cm) and those with STND (< 2.0 cm). Methods This was a retrospective study in which 266 patients who underwent NSM with immediate breast reconstruction between January 2008 and December 2014 at a single institution were enrolled. Of these patients, 21 were excluded because of loss to follow-up; thus, 245 patients were finally analyzed. All patients underwent preoperative breast magnetic resonance imaging and intraoperative frozen biopsy. Results The mean age of the patients was 42.4 years. STND was identified in 128 patients, and LTND in 117 patients. The mean follow-up period was 60.5 months. There were no significant differences between the 2 groups with respect to lymphovascular invasion, nuclear grade, nodal status, and subtype (p = 0.339, 0.372, 0.955, and 0.338, respectively). The STND group had significantly smaller tumors than the LTND group (p = 0.005). The median TND in the STND and LTND groups was 0.7 cm and 3.0 cm, respectively. Locoregional recurrence was reported in 4 patients in the STND group (3.1%) and 6 (5.1%) in the LTND group. A total of 3 patients died (1.2%; 2 in the STND group and one in the LTND group). There was no significant difference between the 2 groups with respect to disease-free survival or local recurrence-free survival (p = 0.334 and p = 0.477, respectively). Conclusion The long-term oncologic outcomes of patients treated with NSM did not significantly differ according to TND when the intraoperative frozen biopsy was negative for tumor cells.

Microarray technology is an interdisciplinary technique that promises a revolutionary progress toward better health and improved quality of life. The paper focuses on the development of an efficient software package, equipped with already well-known methods; also some new methods are proposed that will allow the processing and analysis of thousands of genes on microarray images. The microarray analysis software package (called SmartArray), newly proposed in this paper verifies, through microarray analysis, dramatic changes in the mRNA, protein, and activity level in the rat retina during light deprivation, which have been demonstrated in previous biological experiments. The analysis results demonstrate that SmartArray can successfully find many changes in gene expression levels in each subarray and classify them according to their significance.

조직에서 훈련전이에 대한 관심이 증대됨에 따라 인적자원개발 분야에서는 훈련전이에 영향을 미치는 요인들을 측정하기 위한 타당성 높은 도구에 대한 필요성이 증가하였다. 이러한 요구를 만족시키기 위한 노력의 일환으로 Holton과 그의 동료들은 조직의 훈련전이에 영향을 주는 핵심적인 체제 요인들을 측정하기 위한 학습전이체제목록(Learning Transfer System Inventory)을 개발하고 이에 대한 타당성 검증을 미국 및 일부 국가에서 시도해 왔다. 국내에도 LTSI를 활용한 몇몇 연구들이 있었다. 그러나 그 연구들은 순번역․역번역, 주관적․객관적 평가, 파일럿 테스트 등의 엄격한 번역과정을 거치지 않았을 뿐만 아니라, 타당성이 검증되지 않은 LTSI를 사용하였다는 제한점이 있다. 따라서 이 연구는 철저한 번역과정을 통해 LTSI를 한국어에 적합하게 번역하고, 그에 대한 타당성을 다양한 국내 사기업 및 공기업에서 검증하였다. 또한 이 연구는 타당화된 LTSI 한국어 버전을 활용하여 국내 사기업과 공기업 간에 학습전이체제특성에 있어서 차이가 있는지를 검증하였다. 그 결과 LTSI 한국어 버전은 기존 LTSI 16개 요인 중 세 개의 요인이 한 개의 요인으로 통합되어 총 14개의 요인, 64개 문항으로 구성되는 것이 타당한 것으로 나타났다. 또한 총 14개의 타당화된 학습전이풍토 요인 중 한 개의 요인(personal outcomes - negative factor)을 제외한 13개의 요인에서 사기업과 공기업 사이에 통계적으로 유의미한 차이가 나타났다.

Purpose The recent trend in breast cancer treatment is to minimize axillary dissection. However, no pattern of axillary metastasis has been precisely established. The purpose of this study was to evaluate the metastatic lymphatic pattern using near-infrared fluorescence imaging with indocyanine green (ICG) in breast cancer with cytologically proven axillary metastasis. Methods This was a prospective single-center study. We evaluated 147 patients with breast cancer involving cytologically proven axillary metastasis, and compared physiological and nonphysiological lymphatic metastasis. Results We performed lymphatic mapping for 64 patients who exhibited level II lymphatic flow on near-infrared fluorescence imaging with ICG, and found that all had axillary metastasis: 51 patients who did not receive neoadjuvant chemotherapy (NAC) and 13 patients post-NAC. Of patients who did not receive NAC, 32 had physiological lymphatic metastasis and 19 had nonphysiological lymphatic metastasis. The risk factors for nonphysiological lymphatic metastasis were age ≥55 years, high Ki-67 index (>20%), and perinodal extension in both univariate and multivariate analysis (p

Purpose Subsequent to the American College of Surgeons Oncology Group (ACOSOG) Z0011 and After Mapping of the Axilla: Radiotherapy or Surgery (AMAROS) trials, complete axillary lymph node dissection is not routinely performed, even in cases where metastatic sentinel lymph nodes are detected. We investigated the percentage of N2 or N3 stages in T1–2 invasive breast cancer patients with no lymphadenopathy and developed a nomogram to predict the possibility of N2 or N3 stages in these patients. Methods We retrospectively reviewed the charts of invasive breast cancer patients who were clinically N0 stage, but had a positive sentinel or non-sentinel lymph node detected on sentinel lymph node biopsy. The association of potential risk factors with known outcomes (N2 or N3 stages) was tested using logistic regression analysis. Variables with p

Purpose This study aimed to evaluate the effects of sentinel lymph node biopsy (SLNB) on recurrence and survival after neoadjuvant chemotherapy (NAC) in breast cancer patients with cytology-proven axillary node metastasis. Methods We selected patients who were diagnosed with invasive breast cancer and axillary lymph node metastasis and were treated with NAC followed by curative surgery between January 2007 and December 2014. We classified patients into three groups: group A, negative sentinel lymph node (SLN) status and no further dissection; group B, negative SLN status with backup axillary lymph node dissection (ALND); and group C, no residual axillary metastasis on pathology with standard ALND. Results The median follow-up time was 51 months (range, 3-122 months) and the median number of retrieved SLNs was 5 (range, 2-9). The SLN identification rate was 98.3% (234/238 patients), and the false negative rate of SLNB after NAC was 7.5%. There was no significant difference in axillary recurrence-free survival (p=0.118), disease-free survival (DFS; p=0.578) or overall survival (OS; p=0.149) among groups A, B, and C. In the subgroup analysis of breast pathologic complete response (pCR) status, there was no significant difference in DFS (p=0.271, p=0.892) or OS (p=0.207, p=0.300) in the breast pCR and non-pCR patients. Conclusion These results suggest that SLNB can be feasible and oncologically safe after NAC for cytology-determined axillary node metastasis patients and could help reduce arm morbidity and lymphedema by avoiding ALND in SLN-negative patients.

ight is not possible. Solutions are constructed as a sequence of alternate turning arcs that follow a reference circle and include piecewise linear transitions between turning radii. A comprehensive Turning Dubins Vehicle (TDV) solver is presented to handle the spectrum of relative distances and headings between aircraft initial state and a landing runway approach end. This solver generates the minimum number of turning sequences for the TDV, thus providing a minimum length landing ight plan. Example solutions are used to illustrate the TDV solver.

Safe aircraft emergency management requires a two-stage real-time response: rst identify the problem, then alter the ight plan and constrain e ector commands to maximize chances of a safe landing. In cases of degraded aircraft performance, commands must respect new ight envelope limits to avoid loss-of-control. In previous work we have proposed an intuitive approach to adaptive ight planning and guidance in which feasible trim states are sequenced into emergency landing ight plans. Sets of feasible trim states and transitions between these states are derived from post-failure aircraft dynamics, enabling the ight planner to focus on real-time generation of landing trajectory geometry (kinematics) without risk of violating dynamics constraints. This paper integrates the guidance and planning algorithms required to autonomously discover the ight envelope and then to plan a path (in real-time) to a nearby landing runway. Our method accommodates nontraditional ight envelope constraints, including cases in which the aircraft cannot maintain straight and/or level ight. Two F-16 control surface jam failure cases are used to illustrate algorithm integration and performance.

This paper describes an analytic real-time emergency landing trajectory planner applicable in situations where an aircraft experiences severe damage or failure(s) that contract the feasible lateral plane ight envelope. Solutions are constructed as sequences of spirals that follow a reference arc, extending a traditional Dubins path solver to handle cases in which an aircraft cannot y straight. A comprehensive Turning Dubins Vehicle (TDV) solver is presented to handle the spectrum of relative distances and headings between aircraft initial state and the landing runway approach end. This solver is shown to generate minimum-distance landing paths. Example solutions are presented with future work aimed at assessing the impact of transitions and disturbances as well as application to specic damage/failure scenarios.