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We investigated the relationship between the prognostic importance of anatomic tumour burden and subtypes of breast cancer using data from the Korean Breast Cancer Registry Database. In HR+/HER2+ and HR−/HER2−tumours, an increase in T stage profoundly increased the hazard of death, while the presence of lymph node metastasis was more important in HR+/HER2+ and HR−/HER2+ tumours among 131,178 patients with stage I–III breast cancer. The patterns of increasing mortality risk and tumour growth (per centimetre) and metastatic nodes (per node) were examined in 67,038 patients with a tumour diameter ≤ 7 cm and 3 or 4 nodes. The interactions between the prognostic significance of anatomic tumour burden and subtypes were significant. The prognostic relevance of the anatomic tumour burden was non-linear and highly dependent on the subtypes of breast cancer.

Objective : To evaluate the value of breast density change of mammography and breast MRI as a predictive marker for a response to postoperative anti-hormone therapy by targeting ER-positive postmenopausal breast cancer patient Methods : Density change of mammography, breast MRI density being taken just before start of anti-hormone therapy, mammography being performed after 6 months, 1 year, 2 years thereafter and breast MRI being performed 1 year after start of therapy will be measured by volpara and 3D-MR method. Molecular profile including ER expression level that has a relation with response rate to anti-hormone therapy will be analyzed and outcome will be evaluated based on disease free survival and overall survival. Recurrence rate of each group was estimated based on the data of the patients in breast center of Seoul National University Hospital, 2006-2011, who underwent surgery of ER-positive breast cancer. Among 1065 persons, 7.5% (80/1065) showed recurrence rate and among these, recurrence rate of patients who took AI was 6.9% (12/175). Among these, based on MDR 5% cutoff, 1.6% vs 9.8% was represented. By designating recurrence rate as 1.5%, 9.5% and assuming dropout rate by refusal to clinical test as 10%, registration goal was set at total 411 persons based on each 137, 274 persons per each group. Results : (this is interim analysis) From 2012, total 156 patients are enrolled, among them, 32 patients were eliminated (affirmative consent, switched to Tamoxifen, recurrence and etc). From now total 124 patients are on-going to this study. Compare with Non AI group, breast density change of AI group is much decreased from base line study and it is statistically significant. (1 year follow up – base line, 2 year follow up– base line ; -12.2%, - 18.6% vs - 7.6%, -15.3% P-value 0.002, 0.009 respectively) Only one patient was relapsed within 5 year and there were no death. Psychological anxiety, medication compliance and side effects analysis were done. Psychological anxiety about disease and medication were improved as time goes by (p Discussion : 70% of breast cancer is ER-positive breast cancer. Endocrine therapy (ET) has been clarified as an effective target therapy in large scale, prospective randomized trial and up to the present, it has been settled down as a standard therapeutic method of ER-positive breast cancer. As a result of 20 years' follow-up after intake of AI (aromatase inhibitor) and 20 years' follow-up after intake of tamoxifen, recurrence was represented as 2-2.5% and at present, clear mechanism of such resistance and predictive biomarker have not been clarified. Due to this resistance, all the ER-positive breast cancer patients are forced to receive anti-hormone therapy for 5 years or 10 years. According to the taking AI, breast density is significantly decreased compare Non AI group. Of course need more follow up data and analysis, but we can confirm a meaning of endocrine responsiveness of breast density change being measured after anti-hormone therapy as predictive surrogate. Citation Format: Kim Y, Lee E, Lee H-B, Kim KE, Ju YW, Jung JG, Moon H-G, Noh D-Y, Han W. Prospective study analyzing value of breast Density change predicting ENdocrine therapy response in postmenopausal women taking adjuvant ARomatase inhibitor [DEAR study] (interim 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 P4-14-15.

Purpose: Sentinel lymph node biopsy (SLNB) lowers morbidity of lymphedema then axillary lymph node dissection (ALND). However, there has been concern about incidence of lymphedema after SLNB especially when the number of harvested nodes during sentinel node biopsy procedure is more than a few. In this study, we assessed lymphedema incidence and its risk factors including the number excised lymph nodes in patients who underwent SLNB. Methods: Between January, 2011 and April, 2012, the records of 910 consecutive patients who underwent breast surgery with axillary staging (SLNB/ALND) for breast cancer at Seoul National University Hospital were reviewed. Lymphedema was assessed by circumferential upper extremity measurements. The lymphedema was defined as > 1cm for either the upper arm or the forearm. Patients with clinical records of the treatment for lymphedema in the rehabilitation clinic were regarded as having lymphedema. Univariate and multivariate analyses were performed to identify potential risk factors associated with lymphedema. Association of number of excised lymph nodes with lymphedema was analyzed by Spearman rank correlation coefficient. Results: At median follow-up of 69.8 months, 231 patients (25.4%) presented with lymphedema. In univariate analysis, body mass index (BMI) (P Conclusion: The risk of lymphedema is multifactorial in breast cancer surgery and adjuvant treatments. In SLNB alone patients, higher BMI was only significant factor correlated with lymphedema. Excised number of lymph nodes during sentinel biopsy procedure was not associated with lymphedema. Citation Format: Ju YW, Jung JG, Kim KE, Kim Y, Lee E, Lee H-B, Moon H-G, Han W, Noh D-Y. Breast cancer-related lymphedema: Morbidity of sentinel node biopsy [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 P2-14-15.

Background: Immune cells in the tumor microenvironment play an essential role in tumor progression and regression. However, immunologic characteristics and their prognostic role have not been clearly identified in breast cancer patients. This study aimed to evaluate the immunologic characteristics and their prognostic role in breast cancer patients. Methods: This study enrolled pathologically proven stage I-III breast cancer patients. We performed immunohistochemical staining in stromal tumor-infiltrating lymphocytes (TILs) using 10 immune markers (PD-1, PD-L1, PD-L2, IDO, TIM3, OX40, OX40L, B7-H2, B7-H3, B7-H4) with known/possible clinical relevance. Expression of PD-1, PD-L1, and PD-L2 was also measured in adjacent tumor tissue. Intensity and proportion of the staining was measured for each immune marker. The intensity of immunohistochemical staining (IS, intensity score) was graded as follows: 0 (negative), 1 (weak), 2 (moderate), 3 (strong). The proportion of staining (PS, proportion score) was graded as follows: 0 (stain under 50%). Immune markers were defined as positive with one of the following; IS 1 with PS over 3, IS 2 with PS over 2, IS 3 with PS over 1. Results: A total of 392 patients, 271 (69.1%) luminal A, 36 (9.2%) luminal B, 32 (8.2%) HER2-positive, and 53 (13.5%) triple negative breast cancers were included. In total, PD-1 was expressed by stromal TILs in 130 (33.2%) patients, PD-L1 in 47 (12.0%), PD-L2 in 109 (27.8%), B7-H2 in 225 (57.4%), B7-H3 in 227 (57.9%), B7-H4 in 106 (27.0%), TIM3 in 111 (28.3%), IDO in 96 (24.5%), OX40 in 137 (34.9%), and OX40L in 165 (42.1%). In addition, PD-L1 was expressed in 15 (3.8%) tumor tissue, PD-L2 in 237 (60.5%), and PD-1 was not expressed in tumor tissue. Each breast cancer subtype showed different immunologic characteristics. Expression of PD-1 (stromal TILs) and PD-L1 (Tumor and stromal TILS) was higher in HER2-positive and triple negative breast cancer. By contrast, expression of TIM-3, OX40, and OX40L by stromal TILs were higher in luminal A and luminal B breast cancer. In the univariate analysis, expression of B7-H3 was associated with worse DFS and expression of OX40 and B7-H4 was associated with favorable DFS. Expression of PD-L1, PD-L2, OX40L, and B7-H2 had a tendency of favorable DFS. We devised an immune recurrence score (IRS) using 7 markers with prognostic value (B7-H2, B7-H3, B7-H4, OX40, OX40L, PD-L1, and PD-L2). Patients were classified as high-risk (31 patients, 7.9%), intermediate-risk (265, 67.6%), or low-risk (96, 24.5%) according to 7 immune marker expression. In the multivariate analysis, IRS low-risk (adjusted HR, 0.14; 95% CI, 0.04 – 0.45; p = 0.001) and intermediate-risk (adjusted HR, 0.32; 95% CI, 0.16 - 0.656.42; p = 0.002) had significantly lower risk of recurrence compared with high-risk. In the subgroup analysis, the prognostic role of IRS were maintained in both luminal A patients and non-luminal A patients. Conclusions: This study identified immunologic characteristics of breast cancer patients using 10 immune markers. In addition, we devised an IRS with 7 immune markers which may predict recurrence in stage I-III breast cancer patients. Citation Format: Lee D-W, Ryu HS, Lee K-H, Jin M-S, Woo G-U, Suh KJ, Yang Y, Kim H-J, Lee H-B, Kim T-Y, Moon H-G, Han W, Park IA, Noh D-Y, Im S-A. Immune recurrence score (IRS) using 7 immunoregulatory protein expression can predict recurrence in stage I-III breast cancer patients [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 P2-07-09.

A large proportion of breast cancer patients receive hormonal therapy as their adjuvant treatment options. For postmenopausal women, the initial choice for the hormonal therapy is aromatase inhibitor (AI), and tamoxifen (TM) is reserved for women experiencing severe side effects against AI or having low bone density. An important but unresolved clinical question regarding the use of AI in postmenopausal women is the safety of AI regarding the risk cardiovascular events. Studies have shown inconsistent results over the cardiovascular safety of AI and TM. In this study, we investigated the risk of developing cardiovascular and cerebrovascular events in women with breast cancer who receive hormonal therapy using AI, TM, or both. To this end, we used the National Health Insurance Sharing Service in Korea which is provided by National Health Insurance Service. The database provides anonymized insurance data for research purposes after the approval of the review committee. In the database, we identified 47,569 women with the age older than 55 who were diagnosed with breast cancer. Patients were classified as no hormonal treatment group (n=18,807), AI group (n=19,584), TM group (n=7,081), or Switch group (n=2,097). The Switch group was defined as the women with history of both AI and TM prescriptions. During the studied period, a total of 2,032 cardiovascular or cerebrovascular events (CVE) were recorded. Overall, the women prescribed with TM had significantly less hazard ratio for developing CVE when compared to the women who did not receive any hormonal treatment (HR 0.809 95% C.I. 0.706-0.928). However, this protective effect of tamoxifen was not observed in either AI or Switch group (HR 0.917 95% C.I. 0.833-1.010, and HR 0.856 95% C.I. 0.695-1.053, respectively). The protective effect of TM was also similar in women older than 60 (HR 0.808 95% C.I. 0.696-0.938). The cardiovascular and cerebrovascular protective effects of tamoxifen was also substantial in high risk women defined by their family history of cardiovascular diseases and the diagnosis of hypertension or diabetes. Our results suggest that the use of TM is associated with a substantial protective effect against developing cardiovascular or cerebrovascular events in women with breast cancer. However, the protective effect was not observed for women receiving AI. Our data suggest the potential tailored approach in hormonal treatment in breast cancer patients who are at high risk of cardiovascular of cerebrovascular events. Citation Format: Moon H-G, Choi SH, Park Y, Jung JG, Ju YW, Kim KE, Kim Y, Lee E, Lee H-B, Han W, Noh D-Y, Yoon H-J. A nationwide data on the cardiovascular protective effect of tamoxifen and aromatase inhibitor in postmenopausal women with 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 P4-14-09.

This abstract was not presented at the conference. Citation Format: Lee H-B, Kim KE, Ju YW, Jung J-G, Ryu H-S, Lee SB, Lee JW, Lee HJ, Kim M-S, Kwon S, Kim J, Kim C, Moon H-G, Noh D-Y, Ahn S-H, Park I-A, Kim S, Yoon S, Kim A, Han W. 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 P2-07-10.

Introduction: Estrogen receptor is expressed in 75% of breast cancers and is related to a relatively indolent phenotype. Yet, up to 25% of these tumors develop resistance to endocrine therapy. Alternative splicing events are observed in almost every hallmarks of cancer, implying that dysregulation of splicing and cancer progression are closely related. The purpose of this study was to detect splice variants related to endocrine resistance in hormone receptor(HR)-positive breast cancer. Methods: RNA sequencing data of 455 HR-positive patients with documented endocrine treatment from The Cancer Genome Atlas (TCGA) database was used for analysis. Splice variants of 96 ESR1 pathway-related genes were detected using a data-mining algorithm recognizing spliceomic heterogeneity. A differential analysis of splice variants between 48 endocrine therapy-resistant and 407 endocrine therapy-responsive patients was performed to discover isoforms frequently detected in endocrine-resistant tumors. Isoforms related to endocrine resistance was further analyzed using whole transcriptome sequencing data from 59 HR-positive invasive breast cancer patients (24 endocrine therapy-resistant, 35 endocrine therapy-responsive who underwent operation at Seoul National University Hospital. Results: Of 96 ESR1 pathway-related genes, 17 genes showed statistically different splice variant isoforms frequencies (AKT1, ATF2, ATF4, CALM2, CALM3, CREB1, EGFR, ESR1, ESR2, GRM1, HRAS, HSP90AA1, OPRM1, PIK3R3, PRKACB, SHC1, and SHC4). A differential analysis of these isoforms using SNUH data confirmed a predominant isoform of HRAS (64.47% vs 57.14%, p-value 0.0037) and a minor isoform of SHC1 (25.53% vs 32.33%, p-value 0.0456) in endocrine therapy-resistant HR-positive patients. In the same analysis using HR-negative patients, the mean isoform percentage was similar between patients with distant recurrence and no recurrence. Potential Spliceomic Signatures Reproduced From Seoul National University Hospital Data Hormone Receptor Positive Hormone Receptor negative GeneMean Isoform % in Resistant SpecimensMean Isoform % in Responsive Specimensp-valueMean Isoform % in Resistant SpecimensMean Isoform % in Responsive Specimensp-valueHRAS64.4757.140.003757.9758.850.8413SHC125.5332.330.045628.3632.580.2551 Conclusions: Phenotype-specific splice variants can be detected using transcriptome sequencing data. Splice variants in HRAS and SHC1 are potential spliceomic signatures that may be used to predict endocrine therapy-resistant breast cancer. Further investigation is warranted to explore the biological role of these isoforms and identify the role of splice variants as a biomarker for endocrine resistance. Citation Format: Lee H-B, Kim M-S, Rhu J, Park JH, Kim KE, Ju YW, Lee E-S, Moon H-G, Noh D-Y, Kim S, Han W. Detection of splice variants related to endocrine resistant hormone receptor-positive breast cancer [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 P2-05-13.

Malignant phyllodes tumor (MPT) which belong to the fibroepithelial neoplasm spectrum is a rare type of breast malignancy, and currently there is no effective targeted approach available for MPT. In this study, we tried to identify key genomic alterations and biologic pathways in MPT by whole exome and RNA sequencing of nine MPT tissues. Whole exome sequencing revealed somatic alterations in EGFR, MED12, PIK3CA, PIK3R1, PDGFRA, PDGFRB, PTEN, and TP53. Transcriptome sequencing showed dysregulation of ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling in MPTs when compared to normal breast or invasive breast cancer tissues. Based on the transcriptome profiles, the MPTs were classified into two subtypes; fibrous subtype with upregulation of stromal genes such as collagens and epithelial subtype with upregulation of E-cadherin and Claudins. The molecular classification of fibrous and epithelial subtypes was validated in 28 paraffin-embedded MPT tissues. The fibrous subtype showed higher mitotic index and increased risk for recurrence when compared to the epithelial subtype. We established a patient-derived xenograft model from one fibrous subtype MPT which harbored somatic mutation in PIK3R1 and PDGFRB. In that model, targeted treatment against PIK3CA/mTOR and PDGFR pathways effectively suppressed the tumor growth in vivo. Our data provide insights on the biologic understanding of MPT and suggest a clinically relevant molecular classification. Furthermore, we show that developing effective targeted approaches in MPT can be possible with genomic profiles and patient-derived xenograft models. The clinical efficacy of targeting PDGFR and PIK3CA/mTOR pathways in MPT should be tested in future clinical trials. Citation Format: Moon H-G, Yun J, Hong BS, Lee E, Lee H-B, Han W, Kim J-I, Noh D-Y, Heo W, Hur S, Kang W, Lee C. Molecular characterization of human malignant phyllodes tumors reveals potential targeted approaches [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 P2-06-01.

Background There are studies suggesting significant association between the patient's comorbidity and perioperative outcomes. In breast cancer, patient comorbidity can also influence the oncologic outcome by affecting the decisions regarding adjuvant treatments. In this study, we examined the long-term oncologic outcome in breast cancer patients who underwent curative surgery according to their pre-existing comorbid conditions. Methods The medical records of 2,501 patients who underwent surgery for primary breast cancer from June 2006 to June 2010 were reviewed retrospectively. The patients were classified into three groups (ASA 1, 2, 3) according to preoperative ASA status determined by the anesthesiologists. Clinico-pathologic characteristics and survival outcomes of the patients were compared among the different co-morbidity groups. Result There were 1,792 (71.6%), 665 (26.6%), and 44 (1.8%) patients in ASA 1, 2, and 3, respectively. Total 95 (3.8%) deaths and 269 (10.8%) recurrences (loco-regional and distant) occurred during the median follow-up period of 71 months. Patients with high comorbidity showed significantly higher rate of death (51 (2.8%), 38 (5.7%) and 6 (13.6%) deaths in ASA 1, 2 and 3 group, respectively, p Conclusion In this study, high comorbidity was related to increased risk of death and recurrence in breast cancer. The increased risk of recurrence in high co-morbidity group was mostly seen in patients who did not receive adjuvant therapies. In patients who underwent the adjuvant therapies, the incidence of serious adverse effects did not differ according to the co-morbidity status. Citation Format: Han J, Lee H-B, Lee E-S, Kang YJ, Kim Y, Choi J, Rhu J, Han W, Noh D-Y, Moon H-G. The association between patient comorbidity and breast cancer survival [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 P2-07-12.

Background: Next-generation sequencing technology allows the simultaneous sequencing of multiple target genes. We developed a gene panel containing 64 genes which were associated with various hereditary cancers. This study was performed to evaluate the frequency of pathogenic mutations associated with hereditary cancer among Korean patients at high risk hereditary breast cancer using multi-gene sequencing panel. Methods: A total of 252 breast cancer patients with high-risk hereditary cancer were included. Among them, 179 patients (71.0%) had multiple primary cancers including breast cancer, 27 patients (10.7%) were diagnosed with bilateral breast cancer at age 40 or younger. Thirty-five patients (13.9%) had breast cancer family history of more than 2 relatives. With the 64-gene panel, sequence variants were detected by next-generation sequencing technology. Results: Sixty seven patients (26.8%) were found to have 77 germline pathogenic mutations, 12 in BRCA1, 13 in BRCA2, 9 in CDH1, 3 in FH, 5 in MSH2, 2 in MSH6, 4 in NAT1, 6 in PTCH1, 3 in RAD51, 7 in RET, 4 in SPINK1, 3 in TP53 and one each in ALK, BRIP1, CHEK2, MLH2, MUTYH, and PTEN. In 20 patients (4.0%), 2 (n=9) or 3 (n=1) pathogenic mutations were detected. In 227 patients with BRCA1/2 negative, CDH1 (n=7), RET (n=7), PTCH1 (n=5), and MSH2 (n=5) were the most prevalent pathogenic mutations. Conclusions: The 64 gene panel detected germline pathogenic mutations in 26.8% of Korean breast cancer patients with feature of hereditary cancer. Mutations of BRCA1, BRCA2, CDH1, RET, and PTCH1 were the most prevalent variants.Mutation carriers were considered as high risk to develop malignancy and recommended to receive genetic counseling and intensive cancer screening. Citation Format: Shin H-C, Yoo T-K, Lee H-B, Moon H-G, Noh D-Y, Han W. Frequency of pathogenic mutation in patients at high risk for hereditary breast cancer [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 P4-06-16.

Ultrafast time-resolved x-ray absorption near edge spectroscopy (XANES) experiment was performed on a magnetite (Fe

In non-osteoporotic postmenopausal women with breast cancer, aromatase inhibitors (AIs) negatively affected bone mineral density (BMD), lumbar spine trabecular bone score (TBS) as a bone microarchitecture index, and hip geometry as a bone macroarchitecture index. AIs increase the risk of fracture in patients with breast cancer. Therefore, we aimed to evaluate the long-term skeletal effects of AIs in postmenopausal women with primary breast cancer. We performed a retrospective longitudinal observational study in non-osteoporotic patients with breast cancer who were treated with AIs for ≥3 years (T-score >−2.5). Patients with previous anti-osteoporosis treatment or those who were given bisphosphonate during AI treatment were excluded from the analysis. We serially assessed BMD, lumbar spine TBS, and hip geometry using dual-energy X-ray absorptiometry. BMD significantly decreased from baseline to 5 years at the lumbar spine (−6.15%), femur neck (−7.12%), and total hip (−6.35%). Lumbar spine TBS also significantly decreased from baseline to 5 years (−2.12%); this change remained significant after adjusting for lumbar spine BMD. The annual loss of lumbar spine BMD and TBS slowed after 3 and 1 year of treatment, respectively, although there was a relatively constant loss of BMD at the femur neck and total hip for up to 4 years. The cross-sectional area, cross-sectional moment of inertia, minimal neck width, femur strength index, and section modulus significantly decreased, although the buckling ratio increased over the treatment period (all P

The purpose of this study was to investigate the correlation of ataxia-telangiectasia-mutated (ATM) protein and p53 expression with clinicopathological features and prognosis in patients with sporadic breast cancers. The expression of ATM and p53 was determined by immunohistochemistry in 420 surgically resected breast cancers. Loss of ATM was observed in 126 out of 407 evaluable cases (31.0%), and was significantly associated with aggressive features with large tumor size, lymph node metastasis, higher tumor grade, and negativity of ER and/or PR. ATM loss was associated with a significantly shorter disease-free survival (DFS) (p = 0.019). Abnormal p53 expression was found in 39.3% of tumors (157 out of 400), conferring a worse DFS as well (p = 0.002). When investigated together, combined ATM and p53 expression status were associated with a worse DFS (p = 0.002). On multivariate analysis, ATM loss and abnormal p53 expression status was an independent predictor of poorer DFS (intact ATM and normal p53 vs. ATM loss and abnormal p53, HR 3.350; 95% CI 1.496 - 7.502; p = 0.003). Furthermore, in patients treated with adjuvant anthracyclines, either p53 alone or p53 combined with ATM significantly influenced DFS (p = 0.004, p = 0.015, respectively). The present study demonstrates that expression of ATM and p53 is an independent prognostic marker in breast cancers, and might be a practical tool for predicting benefits from anthracycline-based adjuvant therapy. Citation Format: Suh KJ, Ryu HS, Lee K-H, Im S-A, Kim T-Y, Kim H, Yang Y, Moon H-G, Han S-W, Oh D-Y, Han W, Kim T-Y, Park IA, Noh D-Y, Bang Y-J. The prognostic significance of ataxia-telangiectasia-mutated (ATM) and p53 expression in breast cancer. [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 P4-07-08.

Background Metabolic syndrome is associated with various malignancies, including breast cancer. Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. NAFLD is frequently observed during chemotherapy, but its clinical implication is unclear. The purpose of this study is to evaluate the prognostic value of NAFLD in patients with stage II/III breast cancer who received neoadjuvant chemotherapy (NAC Tx). Methods The patients with clinical stage II/III breast cancer who received NAC Tx with docetaxel and doxorubicin were enrolled. Treatment sequences were: 3 cycles of NAC Tx → surgery → 3 cycles of adjuvant chemotherapy (AC Tx), or 6 cycles of NAC Tx → surgery, allowing AC Tx at the physician's discretion. NAFLD was determined by ultrasonography (radiologists' decision), non-constrast computed tomography [CT] (the attenuation of liver is less than that of spleen or Results Between 2002 and 2008, 269 patients were enrolled. The median age was 45 (range 18-69), and 51.7% and 28.6% were with hormone receptor and HER2 positive tumors, respectively. The median number of NAC Tx was 3 cycles (range 1-6). NAFLD was observed in 33 (12.4%) patients at diagnosis, 52 (19.3%) after NAC Tx and 71 (26.4%) at the completion of AC Tx. The patients with NAFLD at diagnosis showed shorter overall survival than those without NAFLD (HR=2.688, 95% CI 1.259-5.747, P=0.011). The improvement of NAFLD during NAC Tx was observed in 28 (10.4%, group A) and persistence of NAFLD observed in 24 (8.9%, group B). Group A showed better prognosis in both PFS (HR 0.125, 95 % CI 0.016-0.962) and OS (no event), whereas group B showed worse PFS (HR 2.329, 95% CI 1.280-4.237) and OS (HR 3.721, 95% CI 1.727-8.015) compared to the patients without NAFLD at diagnosis. Conclusions NAFLD at diagnosis was a poor prognostic marker of OS in patients who received NAC Tx. Improvement of NAFLD during NAC TX was associated with good prognosis in terms of PFS and OS. Citation Format: Yang Y, Lee K-H, Kim T-Y, Han S-W, Oh D-Y, Kim T-Y, Han W, Moon H-G, Park IA, Noh D-Y, Im S-A. Prognostic value of non-alcoholic fatty liver disease in stage II/III breast cancer patients who received neoadjuvant chemotherapy. [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 P1-10-11.

Background Immunohistochemistry markers are recognized as a predictive prognostic factor for women with breast cancer. Ki-67 and progesterone receptor (PgR) expression are reported to be independently associated with breast cancer prognosis. Some studies report high Ki-67 expression as a negative predictive marker. Whereas other studies report tendency of similar survival between high and low Ki67 cancers when PgR expression is high. In this study, we examined the prognostic significance of Ki-67 expression under PgR expression status. Methods The records of 2,366 patients were retrospectively reviewed. The patients underwent surgery for primary breast cancer from July 2009 to December 2012 at a single institution. We studied the prognostic significance of Ki-67 expression under PgR expression. We used 20% and 10% as the cut-off value for PgR and Ki-67, respectively. The end point was recurrence-free survival (RFS) evaluated by use of Kaplan-Meier analysis. Result Of the 2,366 analyzed patients, the median follow-up time was 43 months. During follow-up, 44 patients had recurrence, loco-regional recurrence developed in 23 patients and distant recurrence developed in 21 patients. In patients with low PgR expression, high Ki-67 expression group showed significantly worse prognosis compared to low Ki-67 expression group (p=0.005). On the other hand, no significant difference was shown between low and high Ki-67 expression group when PgR expression was high (p=0.637). Also multivariate analysis demonstrated that high Ki-67 expression was an independent prognostic factor only when PgR expression was low. (95% confidence interval [CI], 1.35-10.48; p=0.011) Conclusion This is the largest reported study that prognostic significance of Ki-67 expression is defined by PgR expression. Our study presents that high Ki-67 expression is inversely correlated with recurrence risk in early breast cancer patients only under low PgR expression. At high PgR expression, Ki-67 expression has no influence on breast cancer prognosis. Therefore, attention should be paid to correlation between PgR and Ki-67 expression. Citation Format: Han JH, Kang YJ, Han W, Lee H-B, Kim Y, Yoo T-K, Moon H-G, Noh D-Y. Ki-67 expression is not a valuable predictive prognostic factor when progesterone receptor expression is high in estrogen receptor-positive breast cancer. [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 P5-08-23.

Background Existing evidence strongly suggests that exercise is not only safe but also feasible during cancer treatment. Physical activity is recommended for improving multiple post-treatment adverse effects on bone health, muscle strength, and other quality-of-life measures. Yet, limited evidence exists regarding effect of increased physical activity after diagnosis on symptoms management of breast cancer patients. Methods A total of 422 patients were recruited from July 2010 to July 2011 at two cancer hospitals in Seoul, Korea. Physical activity in sports (PAS) was assessed using Minnesota Leisure Time Physical Activity Questionnaire before and 2 weeks, 3-, 6-, 12-, 24- and 36-months after diagnosis. Physical symptoms including fatigue, pain, arm symptom, and insomnia were measured using EORTC-C30 and BR23. Growth mixture models were used to identify trajectory classes of physical activity patterns. Multivariate analysis was used to find impact of PAS on symptom management using SAS. Results Three distinct PAS groups were identified according to 3-year change patterns: moderate to moderate (MM): 40.8%, none to moderate (NM): 31.1% and moderate to high (MH): 28.1%. The LM and MH group increased PAS from diagnosis but it began to decrease from 1 year after diagnosis. Compared to the MM, the NM and MH reported significantly lower level of fatigue (MM:40.7, NM:32.2, MH:33.7), pain(MM:28.0, NM:25.6, MH:20.6), systemic therapy side effects (MM:26.9, NM:22.6, MH:21.8), and breast symptoms (MM:25.4, NM:21.7, MH:20.2) during active treatment (6 months after diagnosis). Change patterns of quality of life according to trajectory groups At diagnosis2 weeks3 months6 months12 months24 months36 monthsFatigueMM31.3±1.930.2±1.935.3±2.0140.7±2.1137.8±2.1138.5±2.1141.0±2.21NM30.2±1.928.2±1.931.9±2.132.2±2.2233.6±2.135.6±2.2137.8±2.31MH28.8±2.327.4±2.233.0±2.433.7±2.51233.9±2.4136.2±2.5137.1±2.51PainMM15.1±1.531.3±1.9123.2±2.0128.0±2.0123.5±2.0122.0±2.0121.2±1.91NM15.4±1.532.4±2.023.3±2.0125.6±2.122.7±2.021.1±2.123.8±2.01MH17.2±1.828.4±2.3121.2±2.320.6±2.4219.7±2.321.1±2.318.6±2.2Systemic therapy side effectsMM16.8±1.114.3±1.2133.2±1.7126.9±1.5125.4±1.5126.2±1.6128.6±1.71NM15.0±1.114.5±1.235.2±1.7122.6±1.61222.0±1.6124.5±1.7127.7±1.81MH15.6±1.412.9±1.4134.4±2.0121.8±1.81221.8±1.7122.1±1.9124.7±2.01Breast symptomsMM13.8±1.226.4±1.6120.8±1.5125.4±1.6123.6±1.6119.2±1.7119.6±1.71NM13.0±1.224.7±1.6119.6±1.5121.7±1.61222.3±1.7119.9±1.8119.1±1.81MH16.0±1.424.1±1.8119.4±1.820.2±1.81217.8±1.8217.4±2.014.0±1.92*adjusted with age, stage, and radiotherapy 1 p Conclusion The results of the study confirmed that increased physical activity after diagnosis, even with patients who did not exercise at all before diagnosis, helps to control fatigue, pain, systemic side effects, and breast symptoms during treatment. It is necessary to find ways to promote physical activity after diagnosis and help patients to stay active during treatment. Citation Format: Lee JK, Kang D, Choi E-K, Kong S, Lee S-K, Lee JE, Han W, Park YH, Ahn JS, Im YH, Noh D-Y, Nam S-J, Cho J. Impact of increased physical activities after diagnosis on fatigue and overall pain during cancer treatment: A prospective cohort study. [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 P1-10-31.

Background In this study, we aimed to identify demographic and clinical variables that correlate with perceived information provision among cancer patients and determine the association of information provision with decisional conflict (DC). Patients and methods We enrolled a total of 625 patients with cancer from two Korean hospitals in 2012. We used the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire (QLQ-INFO26) to assess patients' perception of the information received from their doctors and the Decisional Conflict Scale (DCS) to assess DC. To identify predictive sociodemographic and clinical variables for adequate information provision, backward selective logistic regression analyses were conducted. In addition, adjusted multivariate logistic regression analyses were carried out to identify clinically meaningful differences of perceived level of information subscales associated with high DC. Results More than half of patients with cancer showed insufficient satisfaction with medical information about disease (56%), treatment (73%), other services (83%), and global score (80%). In multiple logistic regression analyses, lower income and education, female, unmarried status, type of cancer with good prognosis, and early stage of treatment process were associated with patients' perception of inadequate information provision. In addition, Information about the medical tests with high DCS values clarity [adjusted odds ratio (aOR), 0.54; 95% confidence interval (CI) 0.30–0.97] and support (aOR, 0.53; 95% CI 0.33–0.85) showed negative significance. For inadequate information perception about treatments and other services, all 5 DCS scales (uncertainty, informed, values clarity, support, and effective decision) were negatively related. Global score of inadequate information provision also showed negative association with high DCS effective decision (aOR, 0.43; 95% CI 0.26–0.71) and DCS uncertainty (aOR, 0.46; 95% CI 0.27–0.77). Conclusion This study found that inadequate levels of perceived information correlated with several demographic and clinical characteristics. In addition, sufficient perceived information levels may be related to low levels of DC.

Achieving a clear resection margin in breast conserving surgery (BCS) is an important factor in tumor recurrence in breast cancer. To obtain clear resection margins and reduce re-excision rates, some surgeons obtain intraoperative assessments of the margins of excised specimens, using intraoperative frozen biopsy. But intraoperative frozen biopsy has several problems such as low sensitivity or longer operation time. We have previously reported a nomogram for prediction of positive resection margin by integrating preoperatively available clinical and pathologic information. The factors were the presence of microcalcification, mammographic density, tumor size discrepancy between magnetic resonance imaging and ultrasonography, and the presence of ductal carcinoma in situ or lobular carcinoma in needle biopsy specimens. We conducted a prospective trial to examine the accuracy and clinical benefits of the nomogram in 442 breast cancer patients (nomogram group) who underwent BCS between Dec 2011 and March 2013, and compared the clinical outcome with that of the 253 patients (control group) who underwent BCS between Jan 2011 and Oct 2011. For nomogram group, the intraoperative frozen section biopsy was omitted in patients with low nomogram scores. Applying our nomogram did not increase the rate of reoperation due to resection margin positivity when compared to the control group (6.56% vs. 4.25%, respectively, p = 0.22). In the nomogram group, the reoperation rate in patients with low nomogram score who did not undergo intraoperative frozen biopsy was 3.2%, and this is lower than the reoperation rate in the control group. Additionally, we experienced a significant reduction in operation time by 15 minutes when compared to the control group (p In conclusion, our results show that out nomogram for predicting positive resection margin for patients who receive BCS can significantly reduce the operation time without increasing reoperation rate. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-15-04.

Background: The downstaging of the primary tumor and the increase in breast conservation rates seems to be the only clinical benefit of Neoadjuvant systemic therapy(NST) in breast cancer treatment, given that several studies failed to demonstrate an improvement of overall survival compared with postoperative adjuvant chemotherapy. In Europe, S6 trial showed better early outcome in survival in favour of the neoadjuvant chemotherapy group compared to adjuvant chemotherapy group in premenopausal patients without significantly modifying long-term event rates. The aim of this study was to assess a potential advantage in survival by neoadjuvant as compared to adjuvant chemotherapy in young age breast cancer patients. Methods: Between January 2001 and December 2008, 1169 consecutive patients with breast cancer aged under 40 underwent adjuvant chemotherapy before or after surgery. Prospectively collected medical records for all patients were reviewed retrospectively. For the comparison of survival between neoadjuvant versus adjuvant chemotherapy group, cinically T2 and node positive patients were retrieved. Survival curves were derived from Kaplan-Meier estimates and compared by log-rank test. Results: Of the 1169 patients, 203(17.3%) patients were treated with neoadjuvant chemotherapy, and they were grouped as ‘NST’ and ‘non-NST’ according to initial treatment. About 47% patients in each group were clinically T2 patients. (99(47.8%) in NST group, 453(46.9%) in non-NST group) Among them, clinically T2 and node positive patients were 188, 97 patients in NST group, 91 patients in non-NST group each. The median age was 35.11±3.9 years old and HER2 amplification was observed as 23.5%, and they were not different between two groups.(p = 0.146 and 0.941 each) Significant lower hormone receptor expression rate and higher Ki-67 level were observed in NST group(p = 0.03 and Conclusion: A potential advantage of primary over adjuvant chemotherapy in young age breast cancer patients’ survival might be proposed by this results. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-20.

Background The use of breast-conserving surgery (BCS) in patients with large breast tumors downstaged by neoadjuvant chemotherapy (NCT) remains controversial in clinical stage III breast cancer patients because of the possibility of residual tumor and resistance to NCT. The aims of this study were 1) to evaluate the local recurrence (LR) rate depending on the use of NCT and 2) to determine the oncologic safety of BCS after NCT by comparing LR between patients treated with preplanned/downstaged BCS and patients treated with NCT and mastectomy in clinical stage III breast cancer patients. Patients and Methods Between 2000 and 2007, 166 patients with clinical stage III breast cancer received BCS or mastectomy after NCT (NCT group) and 193 patients with clinical stage III breast cancer who underwent surgery first (Surgery group). Among 166 patients of the NCT group, 94 patients (56.6%) received mastectomy after NCT (mastectomy after NCT group), 39 patients (23.5%) received preplanned BCS (preplanned BCS group) and 33 patients (19.9%) received downstaged BCS (downstaged BCS group). The LR rates between the groups were compared. Results At a median follow-up period of 66.9 months (range, 6.5 to 104.1 months), 11 patients in the NCT group and 7 patients in the Surgery group had developed LR. The 5-year LR-free survival rates were 93.6% in the NCT group and 95.9% in the Surgery group and the LR rates were not significantly different between the groups (p = 0.196). In the NCT group, LRs were observed in 6 patients in the mastectomy after NCT group, 3 patients in the preplanned BCS group and 2 patients in the downstaged BCS group. The 5-year LR-free survival rates were 94.4% in the mastectomy after NCT group, 92.0% in the preplanned BCS group and 93.9% in the downstaged BCS group, respectively (p = 0.953). Conclusions Our study demonstrated that the LR was not different depending on the use of NCT in the clinical stage III breast cancer patients. Also, clinical stage III breast cancer patients who received preplanned or downstaged BCS after NCT showed similar LR-free survival rates compared to patients who received mastectomy after NCT. This result supports that BCS after NCT in clinical stage III patients is oncologically safe in terms of LR if primary breast tumor size has became 5cm or less after NCT. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-19.

Background: Recently, the information in the IHC score was reported to be similar to that in the 21-gene Genomic Health recurrence score (GHI-RS). The aim of this study is to develop a nomogram based on Ki67 index to predict recurrence and to validate the nomogram by comparison with CS-IHC4 as well as Adjuvant! Online and St. Galen risk stratification. In addition, we validated our nomogram with external cohort. Methods: We retrospectively analyzed the clinicopathologic characteristics and outcomes of 1,070 postoperative HR-positive breast cancer patients between 2004 and 2007 at the Samsung Medical Center to determine recurrence-free survival (RFS). We constructed nomogram using Cox proportional hazard model and validated externally in a cohort of 1,028 at Seoul National University Hospital. A prognostic model that used classical variables, Adjuvant! Online, St. Gallen risk stratification, and the four IHC markers (IHC4 score) were created and assessed in our cohort by LR-χ2 test using the bootstrapping method. Results: Nomogram showed an area under the receiver operating characteristic curve (AUC) of 0.70 (95% CI, 0.62–0.75) in the training set. The validation set showed a good discrimination with an AUC of 0.65 (95% CI, 0.58–0.72). In LR-χ2 test, the nomogram score was found to be more informative than the IHC4 with CS (LR-χ2 4.0539 [df1], 95% CI; 0.1038–8.004 for CS-IHC4 + nomogram score vs. CS-IHC4). Prognostic significance was more prominent in N1 diseases than in the others (LR-χ2 4.199, 95% CI; 1.496–6.902 for CS-IHC4 + nomogram score vs. CS-IHC4). However, Adjuvant! Online and St. Galen risk stratification did not show any definitive additional prognostic value. Conclusions: We developed and validated a nomogram based on Ki67 index in external patients' cohort. It was compared with CS-IHC4 in our patients' cohort in early HR-positive breast cancers. This study implicates the amount of prognostic information contained in the nomogram is superior to that in the CS-IHC4 score. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-20.

Neoadjuvant chemotherapy has been considered valuable beyond its role in facilitating conservative surgery and improving prognosis associated with pathologic complete response. Predictive factors of response would help to assess the expected individual benefit of this treatment. Bcl-2 and p53 have been mostly investigated predictive biomarker for the efficacy of chemotherapy in breast cancer, however, studies documenting predictive significance of biomarkers in triple negative breast cancer(TNBC) are limited by low n values of patients. Furthermore, studies did not provide consistent result to conclude about predictive value of biomarkers. There is no unique explanation to date to account for such inconsistencies across studies. In the present study, the two most studied inhibitors of apoptosis, the bcl-2 and p53, have been evaluated to assess whether they may play a role in modulating response to triple negative breast cancer to neoadjuvant chemotherapy. From January 2003 to December 2011, 187 patients presenting T1-4 N0-3 M0 primary TNBC were submitted to two different chemotherapeutic regimens before surgery. The first 154 received the doxetaxel/doxorubicin regimen, the remaining 33 were submitted to doxorubicin and cyclophosphamide followed by doxetaxel. The expression of p53, bcl-2 was evaluated in TNBC specimens obtained at diagnosis by core needle biopsy and at postchemotherapy surgery. Overall pathologic complete response(pCR) occurred in 43 of the 187 cases(23%). The pCR rate was superimposable in the patient subgroups with bcl-2-positive or –negative primary tumors. Conversely, p53 expression was significantly associated with higher pCR rate(19.5 vs 73.2%; p = 0.026; in patients with p53- and p53+ breast cancer). In a multivariate regression analysis, after adjusting for tumor and node status, treatment administered, p53 status maintained an independent predictive role for pCR.[relative risk(RR)=6.247, 95% confidence interval (CI)=0.9–39.1] In our homogeneous patient population, pCR was not associated with initial clinical stage, nodal status as well as other clinicopathologic factors. The status of the p53, which is mutated in a high percentage of breast tumors, is a predictive factor for cytotoxic drug activity. By contrast, bcl-2 failed to be related to chemotherapy activity. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-16.

Purpose We aimed to identify whether hormonal receptors change throughout tumor progression, because this may influence management and influence prognosis in breast cancer patients. Patients and Methods From the institution's database, we collected data of 963 patients who developed relapse during their follow-ups. To determine estrogen receptor(ER) and progesterone receptor (PR), we retrospectively reviewed immunohistochemical(IHC) results in both primary and relapsed tumors. Results Among a total of 963 patients, 280 and 683 patients experienced locoregional relapse only and distant metastasis irrespective of locoreginal relapse, respectively. ER in 650 patients and PR in 590 patients from both primary tumor and relapse were identified, revealing a change in 157 (24.2%) and 154 (26.1%) patients, respectively. In patients with distant metastasis, assessment of ER and PR showed an alteration in 86 and 56 patients, respectively. The overall survival related to the change of ER and PR status in primary tumor and relapse was significantly different (log rank, P Conclusion The breast cancer showed alterations of hormone receptor status throughout tumor progression, hat were related to the strategy of treatment and significantly influences survival. Therefore, investigations of hormone receptor at relapse are essential and helpful in breast cancer patient management. Citation Format: Lee E-S, Kim J, Yoo T-K, Kim Y, Han J, Kang YJ, Choi J, Rhu J, Lee H-B, Han W, Noh D-Y, Moon H-G. An alteration of hormonal receptor status throughout tumor progression related to prognosis in breast cancer patients [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 P6-07-19.

Background: Improved understanding of factors affecting the accuracy of breast magnetic resonance imaging (MRI) after neoadjuvant systemic therapy (NST) can lead to more tailored use of MRI in deciding surgical extent after NST. Materials and Methods: We analyzed the imaging and clinicopathologic data of 463 patients who underwent NST. We aimed to investigate whether the molecular subtypes, as well as the use of targeted therapies, were associated with changes in the accuracy of MRI predicting residual tumor extent. Results: The accuracy of MRI predicting the residual tumor extent was most accurate in triple negative breast cancer and was least accurate in Luminal A subtype (Pearson's correlation coefficient of 0.754 and 0.531, respectively). Multivariate analysis suggested estrogen receptor status as an independent factor influencing the MRI accuracy. In HER2−amplified tumors, the use of HER2−targeted agents was associated with less accurate MRI prediction. Dual HER2−blockade by using trastuzumab and pertuzumab resulted in lowest MRI accuracy among the patients treated with HER2−targeted agents. Conclusion: The accuracy of MRI in predicting residual tumor extent was lowest in ER positive tumors treated with NST. In HER2 positive tumors, the use of HER2−targeted agents resulted in less accurate MRI after NST. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-16.

Purpose: While chemotherapy-induced alopecia (CIA) is known to be associated with lower quality of life, the longitudinal effect of alopecia on body image and distress in unknown. This study examined effect of CIA on body image and psychological distress during active breast cancer treatment. Patients and Methods Between July and Dec 2010, we recruited patients with non-metastatic breast cancer who were expected to receive adjuvant chemotherapy (N=411) from two cancer hospitals in Seoul, Korea. After excluding 15 patients with recurrence and 65 patients lost to follow-up, the present analysis is based on 331 patients (80.5%). Participants completed questionnaires on body image, quality of life, alopecia distress at enrollment (before surgery), before chemotherapy (2 weeks post surgery), during chemotherapy (3 months post surgery), and after chemotherapy (6 months post surgery). Body image and quality of life were assessed by the EORTC QoL Questionnaire BR23. Alopecia distress was assessed by the Alopecia Distress Scale, which evaluated distress in 4 domains: physical, emotional, daily activity, and relationship. Results: The mean age of the participants was 46.4 (SD 7.91) year. 44.9% and 37.6% of them had stage I and II breast cancer, respectively. 83.0% of the patients had lumpectomy, and 70.6% and 85.9% had chemotherapy and radiotherapy, respectively. Patients who experienced alopecia had a significantly more negative body image and higher distress compared to those who did not experience alopecia. Body image rapidly decreased at 3 months post surgery coinciding with alopecia, and its effects lasted until 6 months post surgery. Moreover, there was a highly statistically significant association between more negative body image and higher alopecia distress after adjusting for other socio-demographic and clinical characteristics. The patterns and changes in body image and distress comparing patients with and without alopecia are reported in Table 1. Discussion: Health professionals need to develop clinical pathways and education programs to help women with breast cancer manage alopecia distress and negative body image during active treatment. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-14-05.

Background Hormone receptor (HR) positive breast cancers characterized with ER-associated genes are differentiated luminal B from luminal A tumors mainly by proliferation genes. According to NCCN guideline 2011, node positivity has been a main determinant to decide adjuvant chemotherapy with category 1. However, the experts’ panel at the St. Gallen Consensus in 2009 do not provides definite indications to give or withhold chemotherapy in patient group with intermediate criteria including low numbers (1-3, N1) of involved lymph nodes. Thus, in cases of limited number of nodal metastases, the role of biologic factors including Ki67 index needs to be defined. The aims of this study are to evaluate of Ki67 index as a useful surrogate marker to predict recurrence and to avoid unnecessary adjuvant chemotherapy and to develop nomogram based on Ki67 index to determine adjuvant therapeutic options in HR-positive in N0 and N1 breast cancers. Patients and Methods We retrospectively analyzed the clinicopathologic characteristics and outcomes of 953 postoperative HR-positive N0 and N1 breast cancer patients between 2004 and 2007 at the Samsung Medical Center. We constructed nomogram based on Cox regression model using independent factors demonstrated in multivariate analysis and validated externally in a cohort of 895 patients treated at Seoul National University Hospital. Results: In Cox regression multivariate analysis, ER-ve/PgR+ve and Ki67 index were identified as independent factors. Nomogram base on Cox-regression model showed an AUC of 0.75 (95% CI, 0.72−0.77) in the training set. The validation set showed a good discrimination with an AUC of 0.63 (95% CI, 0.60−0.66). We defined low nomogram score as less than 53, and high nomogram score as 53 or more from the cut-off value of the nomogrma ROC curve. Patients who received anthracycline-containing adjuvant chemotherapy with high nomogram scores showed better RFS with statistical significance than those who did not receive anthracycline-containing adjuvant chemotherapy with high nomogram scores (p Conclusion: Ki67 index is useful as a valuable surrogate marker to predict recurrence and to avoid unnecessary chemotherapy. Nomogram based on Ki67 index is constructed and validated to determine adjuvant therapeutic options in HR-positive N0 and N1 breast cancers. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-12-19.

Purpose Physical activity (PA) has been shown to benefit cancer patients’ physical functioning, emotional well-being, and symptom management. Moderate PA may reduce the side effects of breast cancer treatment and improve quality of life, but most of the studies have been conducted after active treatment was completed and there is little data on patterns of PA during active treatment. This study aims to evaluate patterns and changes in physical activity among breast cancer patients during active treatment. Patients and Methods We recruited 411 women with non-metastatic breast cancer between July 2010 and Dec 2010 from two major cancer hospitals in Seoul, Korea. Trained researchers interviewed participants at enrollment (before surgery), and at 2 weeks, 3 months, and 6 months post surgery. Intensity and duration of PA were assessed using the Minnesota Leisure Time Physical Activity Questionnaire, and energy expenditure (the average calories spent per day) was calculated as metabolic equivalents (METs). Quality of life (EORTC), fatigue (BFI), socio-demographic and clinical characteristics were also assessed. After excluding 15 patients with recurrence during follow-up and 65 patients were lost to follow-up, the final sample size was 331 patients (80.5%). Results The mean (SD) age and BMI of study participants were 46.4 years and 23.3kg/m2 (SD 3.35). 83.7% of women had lumpectomy, and 70.6% and 85.9% had adjuvant chemotherapy and radiotherapy respectively. Breast cancer patients were most likely to spend their energy in lifestyle (walking and driving) and leisure (shopping, reading, and watching TV) activities but spent little energy in sport activities (Table). Conclusion PA declined after the surgery and gradually recovered at 3 and 6 months post surgery but it did not return to the baseline level. Breast cancer patients may need encouragement and support to perform more intensive physical activities during active treatment. *Acknowledgement: The research was accomplished by the support from AMOREPACIFIC and Korea Breast Cancer Foundation. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-12-10.

Purpose: One of substudies of the prospective trials aimed to evaluate the usefulness of serial [18F] 2-fluoro-2-deoxy-D-glucose-positron emission tomography ([18F] FDG-PET) for predicting pathological complete response (pCR) in stage II/III breast cancer with preoperative chemotherapy (PST). Methods: Serial PET was undertaken in 57 breast cancer patients enrolled in three different neoadjuvant trials: 35 patients from a phase II study with paclitaxel/gemcitabine/trastuzumab with ClinicalTrial.gov NCT 00532857, 9 patients from a phase Ib study with paclitaxel/gemcitabine/lapatinib with ClinicalTrial.gov NCT 01133912, and 13 patients from a phase Ib with paclitaxel/gemcitabine/sunitinib with ClinicalTrial.gov NCT0 1070706. All patients received 6 cycles of PST followed by surgery and radiotherapy. We assessed the peak standardized uptake value (SUVp) in the primary tumor at the baseline and after the 2nd cycle (37 patients) or after completion (20 patients) of 6 cycles of PST, and calculated the reduction rate (RR) of the SUVp. Pathological response was classified into pCR and non-pCR. To compare the mean of SUVp and RR of SUVp between different response groups, two-way tables and chi-square tests were used Results: Fifteen (40.6%) of 37 patients who took repeat PET after the 2nd PST and 15 (75%) of 20 patients after completion of PST achieved a pCR with overall pCR rate of 52.6% in the primary tumor. In patients with repeat PET after the 2nd PST, post-treatment SUVp and RR of the SUVp in primary tumors were significantly different by the pathological response (post-treatment SUVp, 1.54 ± 0.63 in pCR vs 2.54 ± 1.06 in non-pCR, P=0.002; RR of the SUVp, 79.2% ± 11.9% in pCR vs 68.9% ± 15.4% in non-pCR, P=0.03). However, in patients with repeat PET after completion of PST, there were no statistical differences of these values (post-treatment SUVp, 1.09 ± 0.63 in pCR vs 1.29 ± 0.36 in non-pCR, P=0.42; RR of the SUVp, 83.7% ± 14.0% in pCR vs 67.5% ± 21.1% in non-pCR, P=0.17) Conclusions: This study demonstrated that repeat PET after the 2nd cycle of PST, not after completion of PST could predict pCR in stage II/III breast cancer with preoperative chemotherapy. Acknowledgement NCC Grant #0910320. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-01.

BACKGROUND: Several serum markers are used in management of breast cancer patients. Among these, tissue polypeptide specific antigen (TPS) has been recently proposed as a potential new marker for breast cancer. METHODS: We reviewed the records of 2247 patents with breast cancer treated between November 2000 and December 2007. We evaluated the association between clinicopathologic features and recurrence free survival with preoperative TPS. RESULTS: Among 2271 breast cancer patients, elevated preoperative TPS level (TPS>80 U/L) were identified in 479 patients (21.1%). Age (>45), tumor size (>2cm), tumor stage, nodal metastasis, progesterone receptor, Ki-67, recurrence and visceral metastasis were associated with elevated TPS levels. 193 patients had evidence of relapse. Elevated TPS were associated with poor recurrence free survival. (P CONCLUSION: Elevated preoperative TPS levels are associated with poor breast cancer outcome. Preoperative TPS can be a valuable prognostic marker for breast cancer. Figure available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-15.

Background: Recently indentified genetic variants from genome-wide association studies of breast cancer have not been validated in Asian population except for Chinese. We sought to confirm the association in ethnically distinct Korean women and to make genetic risk assessment model using multi-gene markers Materials and Methods: 3321 invasive breast cancer patients operated in Seoul National University Hospital and 3500 healthy control women from a population based cohort were genotyped for 5 single nucleotide polymorphisms (SNPs) using Taqman assay. The SNPs genotyped were rs2046210 (6q25.1), rs4973768 (3p), rs2981582 (FGFR2), rs3803662 (TNRC9), and rs889312 (MAP3K1). Results: The five SNPs were significantly associated with the risk of breast cancer in dominant, recessive, and co-dominant model (p-values from 0.012 to 3.41E-08). Minor allele frequencies were between 0.2 and 0.5. Odds ratios were between 1.14 and 1.51. Multi-gene logistic regression risk model was made with this 5 SNPs. Women who have all protective variants showed odds ratio of 0.43, while women who are homozygous for risk variants in all 5 SNPs showed odds ratio of 2.36 compared with women with the most common genotype. Conclusion: We found that 5 SNPs from GWAS in mostly women of European ancestry were also significantly associated with breast cancer risk in Korean women. The multi-gene risk assessment model might be useful to classify women into relevant risk groups. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-19.

Berberine is a pure phenanthren alkaloid isolated from the roots and bark of herbal plants such as Berberis, Hydrastis canadensis and Coptis chinensis. Berberine has been established to inhibit the growth of breast cancer cells, but its effects on the drug resistance and anoikis-resistance of breast cancer cells have yet to be elucidated. Anoikis, or detachment-induced apoptosis, may prevent cancer progression and metastasis by blocking signals necessary for survival of localized cancer cells. Resistance to anoikis is regarded as a prerequisite for metastasis; however, little is known about the role of berberine in anoikis-resistance. We established anoikis-resistant cells from the breast cancer cell lines MCF-7 and MDA-MB-231 by culturing them on a Poly-Hema substratum. We then investigated the effects of berberine on the growth of these cells. The anoikis-resistant cells had a reduced growth rate and were more invasive than their respective adherent cell lines. The effect of berberine on growth was compared to that of doxorubicine, which is a drug commonly used to treat breast cancer, in both the adherent and anoikis-resistant cell lines. Berberine promoted the growth inhibition of anoikis-resistant cells to a greater extent than doxorubicine treatment. Treatment with berberine-induced cell cycle arrest at G0/G1 in the anoikis-resistant MCF-7 and MDA-MB-231 cells as compared to untreated control cells. In summary, these results revealed that berberine can efficiently inhibit growth by inducing cell cycle arrest in anoikis-resistant MCF-7 and MDA-MB-231 cells. Further analysis of these phenotypes is essential for understanding the effect of berberine on anoikis-resistant breast cancer cells, which would be relevant for the therapeutic targeting of breast cancer metastasis.

Background: According to the American College of Surgeons Oncology Group Z0011 trial, complete axillary lymph node dissection (ALND) did not affect survival of patients with clinical T1-T2 invasive breast cancer and one to two sentinel lymph nodes (SLNs) metastases treated with lumpectomy, adjuvant systemic therapy, and radiation therapy. A significant proportion of breast cancer patients may not require ALND, in whom intraoperative analysis of SLNs can be omitted reducing operation time and cost. The aim of this study was to develop a nomogram predicting three or more axillary lymph nodes (ALNs) metastases based on preoperative imaging and clinicopathological factors. Methods: The training set consisted of 1030 patients with clinical T1-T2 invasive breast cancer and clinically negative ALN who received surgery at Seoul National University Hospital (SNUH) between January 2010 and December 2013. Preoperative imaging techniques including ultrasonography (US), computed tomography (CT), positron emission tomography (PET), and clinicopathological features associated with three or more ALN metastases were evaluated by logistic regression analysis. A nomogram predicting three or more ALNs was developed with statistically significant factors. The validation set consisted of 781 independent patients who received surgery at SNUH between January 2014 and December 2015. Results: Of the 1030 patients, 89 (8.6%) had three or more ALN metastases. Multivariate analysis showed that three or more ALN metastases was independently associated with tumor size (cm) by US (p Conclusion: Patients with a strong possibility of three or more ALNs metastases can be identified using preoperative imaging methods including US, CT, and PET. The nomogram measuring this prospect may be valuable in skipping intraoperative analysis of SLNs with advantage of reduced operation time and cost. Citation Format: Park JH, Ju YW, Kim KE, Rhu J, Kim Y, Lee E, Lee H-B, Moon H-G, Noh D-Y, Han W. Nomogram predicting axillary lymph node metastases to skip intraoperative analysis of sentinel lymph nodes [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 P3-01-14.

The quantum efficiency and luminescence properties of double activated terbium aluminum garnet samples were investigated in the present study. A mathematical procedure and PL measurement system are developed for express analysis of quantum efficiency of luminescent materials. The energy-level diagram was proposed to explain the luminescence mechanism. Application of TAG:Ce,Eu with improved CIE and CRI in LED device is demonstrated.

The crystallization of α-Fe2O3/α-Al2O3(0001) thin films has been studied using real-time synchrotron x-ray scattering and atomic force microscope. In the sputter-grown amorphous films of various thicknesses at room temperature, we find the coexistence of α-Fe2O3 and Fe3O4 interfacial crystallites (~50-Å-thick), well aligned to the α-Al2O3[0001] direction. The amorphous precursor is crystallized to the epitaxial α-Fe2O3 grains in three steps with annealing temperature; i) the growth of the well aligned α-Fe2O3 interfacial crystallites to approximately 200-Å-thick, together with the transformation of the Fe3O4 crystallites to the α-Fe2O3 crystallites (< 400°C), ii) the growth of the less aligned α-Fe2O3 grains on top of the well aligned grains (> 400°C), and iii) the nucleation of the different less aligned α-Fe2O3 grains directly on the α-Al2O3 substrate (> 600°C). The surface evolution of the amorphous precursor films after annealing is consistent with the microstructure evolution during the crystallization.

We have measured X-ray reflectivity curves of silicalite-1 microcrystal (MC) monolayers on Si wafers using two different types of molecular linkages, namely, through chloropropyl (CP) groups and through CP/polyethylene imine/CP groups. While the scanning electron microscope images of the two MC monolayers are indistinguishable of molecular linkage between the monolayers and the substrate, their reflectivity curves are distinctively different, despite the fact that the thicknesses of the molecular linkage layers (∼ 10–20 A) are negligibly small compared to the thicknesses of MC monolayers, (∼ 3200 A). We demonstrated that X-ray reflectivity is a very useful tool for the characterization of very thin layers of molecular linkages existing between much thicker MC monolayers and the substrate.

Thermal stability of Ta films grown on Si(100) was investigated by in situ x-ray scattering and ex situ cross-sectional transmission electron microscopy. As a Ta∕Si(100) film was annealed at around 500°C, a uniform Ta–Si interlayer was formed at the interface. This interlayer acts as a diffusion barrier. The Ta film with the interlayer is thermally stable up to 700°C. Meanwhile, Ta films directly annealed to above 640°C exhibit no interlayer formation and transform to randomly nucleated tantalum-silicide phases. Maintaining a uniform interlayer is a critical factor for enhancing thermal stability of Ta∕Si(100) films.

The sapphire orientation dependence of the microstructure of ZnO thin films has been studied in real-time synchrotron X-ray scattering experiments. The ZnO films with a 2400-A-thick were grown on sapphire (001) and sapphire (110) substrates at room temperature by radio frequency magnetron sputtering. The as-deposited ZnO film on sapphire (001) has the only (002) crystal grains, while that on sapphire (110) has not only (002) crystal grains but (100) and (101) additional grains. The ZnO films were changed into fully epitaxial ZnO (002) grains both on sapphire (001) and sapphire (110) substrates with increasing the annealing temperature to 600∘C. The epitaxial relationships of the ZnO grains were summarized as ZnO (00l)[100]//sapphire (00l)[110] and ZnO (00l)[110]//sapphire (110)[001].

Thin films of single c-domain/single crystal ( PbMg 1/3 Nb 2/3 O 3)1-x( PbTiO 3)x, x = 0–0.4 (PMNT) were heteroepitaxially grown on (001) SrTiO 3 and (001) MgO substrates by magnetron sputtering using a quenching process. The lattice parameters of the quenched PMNT thin films were almost the same to the bulk values independently to the lattice parameters of substrates. The quenched PMNT thin films showed stress free structural properties, although the crystal structure of thin films is modified from bulk PMNT. The electromechanical properties are the same to the bulk single c-domain single crystals.

Background: Isolating tumor cells of interest and harvesting histologically pure samples is important for genomic studies. Laser capture microdissection (LCM) is an established method to obtain such purified cell populations for various applications including DNA, gene expression, and single cell analyses. However, LCM possesses problems such as limited optical resolution, cell fragmentation from dissection, and adherence of adjacent tissue to the cells which interrupts with single cell isolation from tissue sections. To overcome these obstacles, we developed a high-throughput pulse laser retrieval system which uses a wavelength that minimizes damage to the cellular content and is processed with a sacrificial layer that provides applicable optical resolution. The aim of this study was to evaluate the performance of the pulse laser retrieval system to provide appropriate samples for genomic analysis using breast cancer tissue. Methods: An indium tin oxide (ITO) coated glass slide was prepared using fresh frozen breast cancer tissue sections of 4㎛ thickness and stained by hematoxylin and eosin. The slide was mounted on the cell isolation machine and imaging was performed with a charge-coupled device camera using a 20× lens. Following identification of the target cells by a pathologist, nano-second pulsed laser (wavelength= 1064nm) was irradiated on the target. Isolated cells were collected in a polymerase chain reaction tube and whole genome amplification (WGA) was carried out using Illustra GenomiPhi V2 DNA Amplification Kit (GE Healthcare Life Sciences, Pittsburgh, PA, USA). Amplified genomic DNA was fragmented and Illumina sequencing libraries were constructed. Sequencing was carried out to generate data with 0.1∼0.2× depth throughout the whole genome for each sample. Copy number variation (CNV) was analyzed by the Variable binning algorithm. Results: Whole genome amplification was performed using bulk tissue and 10 captured single cells from the same specimen. No difference in amplification coverage was observed between the two samples. A CNV analysis of captured single cells revealed similar CNV profiles with those in a matched bulk tumor. Whole exome sequencing (WES) of captured single cells yielded a variant frequency of 15% at a read depth of 15× and 50M base coverage, compared to 0% at 100× and 50M for WES using bulk tumor and 0.5% at 1200× and 100K for targeted sequencing using bulk tumor. Laser capture was performed for DCIS and stromal cells from the same slide. CNV analysis of the two samples showed minimal CNV in normal stromal cells in contrast to DCIS where multiple CNVs were observed. Conclusions: Newly developed pulse laser retrieval system is suitable for capturing single cells for genomic analysis of breast cancer. WGA, WES, and CNV analysis was successfully carried out using the captured single cells and showed no difference in profile compared to those performed with bulk tissue. This method may have the potential to replace LCM for certain applications such as single cell analyses. Citation Format: Lee H-B, Kim S, Lee K-M, Jung Y, Lee AC, Kim J, Bae S, Ryu HS, Yoo T-K, Moon H-G, Noh D-Y, Kwon S, Han W. Genomic analysis of single cells isolated by a pulse laser retrieval system. [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 P1-02-01.

Introduction Fusions genes and it's products are widely applied as biomarker and therapeutic target in hematopoietic cancers. It's role as a “driver” of oncogenic pathway have also been proved in several epithelial solid cancers including prostate, lung and breast cancer. We performed high throughput next generation sequencing technique (RNA-Seq) to identify the novel fusion transcript(FT) in a large set of primary breast cancer samples. Materials and Method Total RNA was prepared using the Illumina® TrueSeq™ RNA sample Preparation Kit and TrueSeq mRNA library was constructed. Clustering was done with HiSeq 2000 and Solexa's sequencing was performed. We used tissues extracted from previously collected 100 fresh-frozen primary breast cancer samples obtained after surgical resection. Among 100 samples, 1 failed to pass the process of RNA sequencing and no expression of fusion transcripts were observed in 7 samples resulting in 92 samples with mRNA-Seq data of fusion transcripts. Fourteen(15.2%) samples were cases with distant metastasis during follow up. Estrogen receptor(ER) was positive in 40(43.5%) samples and 23(25%) were triple negative breast cancer. Results and discussion We detected 958 fusion transcripts among 92 tumors and 58 were chosen for tumor-specific fusion transcript candidate (Fragments per kilo-base of exon per million fragments mapped, FPKM>500 and 3 times higher than average, probability>0.6). Most of the fusion transcripts were “private”, expressed only in one sample. Estrogen receptor(ER) positive breast cancer samples had 29 fusion transcripts and ER negative had 25 fusion transcripts among the 58 tumor-specific candidates. HER2 negative samples exhibited 29 fusion transcripts while 15 were identified in HER2 negative samples. Triple negative sample showed 4 TF candidates. Among the 17 recurrence samples 190 fusion transcripts were identified. Of the 190 fusion transcripts in recurred samples, 24 candidates of recurrence-specific FTs were chosen by it's high expression level (FPKM>300 and 2 times higher than average, probability>0.5). Eight were expressed both in recurred, non-recurred samples and 16 were exclusively expressed in recurred samples. No fusion transcript matched directly with the currently known actionable gene-list owing to the limited number while majority is unexploited. Further validation and functional pathway analysis is under progress to ascertain the role of highly suspected fusion transcripts with oncogenic property. Considering the high incidence of breast cancer world-wide, identification of TF expressed even in only a minor percentage among the whole breast cancer population, if druggable, it can be applicable to large number of patients. Conclusion We performed a whole-transcriptome sequencing with a large set of primary breast cancer samples and detected abundant fusion transcripts. The majority of breast cancer(92.9%, 92/99) had at least one fusion transcript suggesting it's role during the tumorigenesis and progression process. With scarce evidence and confirmed data of actionable fusion gene and it's product, data interpretation for it's clinical utility is rather complicated. Accumulation of these large set data of fusion transcript must serve as a groundwork for future work. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD05-07.

The annealing effects of the thin aluminum silicate films grown on Si(100) by sputtering method were investigated using various physical and electrical measurements. All the films grown at the temperature of 300 °C using sputtering Al2O3 target show an amorphous structure as examined by x-ray diffraction and transmission electron microscopy. The amorphous structure is maintained up to 700 °C and then transformed to crystalline Al1.7SiO0.15O2.85 or mullite phase above the annealing temperature of 800 °C. The conduction process, charge trapping and detrapping characteristics, and trap charge density in metal–oxide–semiconductor structure are influenced by the annealing temperature. The depth profiling data using x-ray photoelectron spectroscopy show that the properties are closely related to the change of the interfacial layer and chemical state under the high temperature annealing. The breakdown characteristics are degraded after the annealing temperature of 900 °C due to the rapid change of the interfacia...

Background: The management of benign intraductal papillomas on core biopsy is controversial. The aim of this study was to determine factors that predict under-evaluation of atypical lesion or malignancy in patients diagnosed with benign papilloma at ultrasound-guided core needle biopsy (CNB), and to develop a prediction algorithm for scoring the possibility of a diagnosis upgrade to atypical lesion or malignancy based on clinical, radiological and pathological factors. Methods: The study enrolled patients diagnosed with benign papilloma at ultrasound-guided CNB who subsequently underwent surgical excision of the lesion. Multivariate analysis was used to identify relevant clinical, radiological and pathological factors that may predict malignancy. Results: A total of 520 CNBs led to a diagnosis of benign papilloma (including benign and atypical papillary lesion), of which 452 CNBs were benign papilloma without atypia. Of the 250 lesions in 234 women were underwent subsequent surgical excision, 44 (17.6%) were diagnosed with atypia or malignancy. Multivariate analysis revealed that bloody nipple discharge, size on imaging ≥15 mm, BIRADS≥4b, peripheral location, and a palpable lesion were independent predictors of atypical lesion or malignancy. A scoring system was developed based on logistic regression models and beta coefficients for each variable. The area under the ROC curve was 0.830 (95% CI: 0.665-0.996), and the negative predictive value was 100% for a score ≤4. Conclusions: A scoring system to predict malignancy in patients diagnosed with benign papilloma at CNB was developed based on five factors: bloody nipple discharge, size on imaging ≥15 mm, BIRADS≥4b, peripheral location, and a palpable lesion. This system was able to identify a subset of patients with lesions likely to be benign, indicating that imaging follow-up rather than surgical excision may be appropriate. Citation Format: Ahn Sk, Moon H-G, Han W, Noh D-Y, Ko E. To excise or not?: Scoring system for predicting malignancy in patients diagnosed with intraductal papilloma at ultrasound-guided core needle biopsy [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 P5-03-04.

Cytokeratin19 (KRT19) is widely used as a biomarker for the detection of disseminated tumors. Using an LC-MS/MS proteomics approach, we found that KRT19 was upregulated in HER2-overexpressing cells and tissues. KRT19 expression was induced by HER2-downstream ERK at the transcriptional level. Another HER2-downstream kinase, Akt, was found to phosphorylate KRT19 on Ser35 and induce membrane translocation of KRT19 and remodeling of KRT19 from filamentous to granulous form. KRT19 phosphorylated by Akt could bind HER2 on the plasma membrane and stabilized HER2 via inhibition of proteasome-mediated degradation of HER2. Silencing of KRT19 by shRNA resulted in increased ubiquitination and destabilization of HER2. Moreover, treatment of KRT19 antibody resulted in downregulation of HER2 and reduced cell viability. These data provide a new rationale for targeting HER2-positive breast cancers.

Interfacial microstructure in GaN nucleation layers was investigated using synchrotron x-ray scattering and transmission electron microscopy. We find that tensile-strained, aligned, interfacial domains coexist with misaligned domains in an as-grown nucleation layer of mostly cubic stacking. The tensile strain originates in a 6/7 matched interfacial structure, wherein 6-Ga atomic distances in GaN match to 7-Al atomic distances in sapphire. The tensile state of the aligned, interfacial domains is preserved during annealing to 1100 °C, while the stacking sequence changes from cubic to hexagonal order. The correlation length of the stacking order is rather short, ∼9 A in the hexagonal phase, compared to that of the cubic phase in the as-grown nucleation layer, ∼25 A, due to stacking faults generated during the kinetically limited transformation.

We investigated the dependence of the crystallinity, strain, and morphological characteristics of epitaxial Y2O3 films grown on Si(111) by ion beam-assisted deposition. Various characterization tools, such as reflection high-energy electron diffraction, X-ray diffraction, high-resolution transmission electron and atomic force microscopy, were used to reveal the physical properties which depend on the assisted energy of the oxygen-ion beam. When the assisted energy of the oxygen-ion beam was applied to grow films, the growth temperature for epitaxy was lowered. The crystallinity was improved and the film was compressed as the assisted energy increased up to 45 eV, while the improvement of crystallinity and the strain increment was suppressed as the assisted energy increased further. Moreover, the morphological shape shows that island growth is induced when ion energy is supplied. That is, when the ion energy is increased, islands are expanded and the surfaces are flattened. The surface morphology yields information on film characteristics, such as crystallinity and strain, both of which depend on the assisted energy of the oxygen ion.

Heteroepitaxial Y2O3 films were grown on oxidized and clean Si (100) surfaces by ion assisted evaporation under an ultrahigh vacuum. The crystalline structure, crystallinity, morphology, and electrical properties were investigated using various techniques. The crystallinity assessed by x-ray diffraction and Rutherford backscattering spectroscopy shows that the films grown on the oxidized Si substrates have better crystallinity and smoother morphology compared to those on the clean Si. As the annealing temperature increases, the crystallinity and morphology are stable for the films grown on the oxidized Si, while those of the films grown on clean Si substrates degrade. The difference between the two films is attributed to the formation of hillocks and a chemical reaction at the interface between the film and SiO2. The low crystallinity, strain change, and the reaction of excess Y in the films grown on the clean Si contribute to the crystalline structure and the formation of hillock. These changes of crysta...