D-Y Noh
Seoul National University Hospital
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Featured researches published by D-Y Noh.
Cancer Research | 2009
J. Yu; Wonshik Han; J. Kim; J. Lee; Eunyoung Ko; Eun-Sook Kim; Hyung-Bae Moon; D-Y Noh
CTRC-AACR San Antonio Breast Cancer Symposium: 2008 AbstractsnnAbstract #2062 nnBackground : Apoptosis in response to inappropriate adhesion or lack of adhesion has been termed anoikis. Resistance to anoikis is regarded as a prerequisite for invasion and metastasis in cancer cells. Recently many studies were performed to understand mechanism of anoikis resistance. However, there have been few studies on the role and mechanism of anoikis resistance in cancer cells. Materials and Methods : Anoikis-resistant MDA-MB-231 cells were induced and selected through culture on polyhydroxyethylmethacrylate (Poly-HEMA) substratum and invasiveness by matrigel invasion assay and drug-resistance to doxorubicin were checked. At the same time, expression of genes were evaluated in anoikis-resistant and adherent MDA-MB-231 cells by cDNA microarray. Pathway analysis on high-expressed genes in anoikis-resistant cells was performed by software(Ingenuity Pathway Analysis) Results : Invasion assays revealed that anoikis-resistant cells were more invasive than adherent cells. Anoikis-resistant cells were also more resistant to doxorubicin than adherent cells. Genes related to NF-kB pathway were highly expressed in anoikis-resistant cells. Therefore, the effect of Bay11-7085, inhibitor of NF-kB, on the growth of anoikis-resistant MDA-MB-231 cells was tested. The blockage of NF-kB pathway inhibited the growth of anoikis-resistant MDA-MB-231 cells. Conclusion : These results demonstrated that anoikis resistance was associated with increased invasiveness and resistance to chemotherapeutic agents and that NF-kB pathway involved in anoikis resistance.nnCitation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2062.
Cancer Research | 2009
Eunyoung Ko; Wonshik Han; D-Y Noh
Abstract #5059 Background In this study, we aimed to investigate the effect of anoikis resistance on drug responsiveness and tumor initiating ability in MDA-MB-231 breast cancer cell line, and to determine whether ABCG2 inhibitor and notch-4 inhibitor will modulate the drug resistance and self renewal ability of anoikis-resistant cells. Methods Anoikis-resistant MDA-MB-231 cells isolated from the MDA-MB-231 cell line using sequential passages through the floating culture system and tested the tumor initiating ability (mammosphere-forming efficacy in vitro and limiting dilution transplantation in vivo), tumor growth rate, and drug responsiveness. Results Anoikis resistant cells were shown to have a greater mammosphere forming efficacy than parent cells (19% versus 2%, P Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5059.
Cancer Research | 2013
Mk Kim; H-G Moon; J Kim; Jw Lee; T-K Yoo; Eunsik Lee; D-Y Noh; Wonshik Han
Introduction: Many somatic mutations, structural alterations, and gene expression changes are causally implicated in oncogenesis and tumor progression, and as a result, affect clinical outcome. Although majority of breast cancer patients have benefits from therapeutics targeting tumor biology, such as estrogen receptor and HER-2, still many patients suffer from disease recurrence and metastasis. More kind of specific target therapies are needed, especially for hormone-resistant tumor and triple-negative breast cancer. Materials and Method: To find novel therapeutic target in breast cancer, here we examine the both whole exome and whole transcriptome of fresh-frozen primary breast cancer tissues from 120 patients whose clinical, pathological, and survival data are available. Patients with Stage IV disease or who received neoadjuvant chemotherapy were excluded. 36 patients had distant metastasis within 5 years from surgery, and 84 patients were NED at least 5 years. RNA and DNA were extracted and qualities were assessed in all samples. Exome and transcriptome sequencing were done using NGS technology (Illumina HiSeq 2000). As a control, exome sequencing was done for 93 normal DNA from matched patients. Single nucleotide variations (SNV) identified in cancer samples on exonic region, nonsynonymous SNV or stop gain/loss, whose quality ≥20, and not found in 93 normal samples were included. SNVs registered in dbSNP135_common or 1000 genome allele frequency >0.001 were excluded.Results and Discussion: We identified 11,684 putative somatic mutations in 7,373 genes. Of them, 6,547 were deleterious or damaging mutation by Provean or SIFT analysis. Mutations were found in potential drug target genes, such as PIK3CA(25), PTEN(3), AKT1(3), ALK(3), ROS1(2), FGFR4(3), FGFR3(2), ERBB2(2), and IDH1(1) etc. In a pathway analysis, mutations in insulin signaling pathway were most dominant. We hypothesized that driver gene and therapeutic target has to have recurrent mutation and gene expression at least more than average expression. We calculated expression “Volume” according to the median normalized FPKM value of individual gene9s RNA-seq data. With a cut-off of 3 or more mutations in each gene, 1,116 genes were selected. After the filtering of Volume Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD4-2.
Cancer Research | 2013
Jw Lee; H-G Moon; Wonshik Han; D-Y Noh
Backgrounds: After completion of human genome project, some genetic variants are discovered and highlighted by genome-wide association studies (GWAS). Single nucleotide polymorphisms (SNP) are considered to be the key variations leading to the various breast cancer susceptibility between each individuals. In 2011, our group has validated 5 SNPs as significant risk factor of breast cancer in Korean women for the first time. Recently, there has been some attempts to find clinical meaning of SNPs in each breast cancer patient. But it was not successful. Methods: Consecutive patients with histologically confirmed primary breast cancer subjected to operative procedures between 2002 and 2009 in Seoul National University Hospital were included for analysis. Patients diagnosed with noninvasive breast cancer (ductal carcinoma in situ and lobular carcinoma in situ) or stage IV breast cancer were excluded. Peripheral venous blood samples were obtained and stored at the time of operation. The SNPs genotyped included rs2046210 (6q25.1), rs2981582 (FGFR2), rs889312 (MAP3K1), rs3803662 (TOX3/TNRC9), and rs4973768 (SLC4A7). SNP genotyping was carried out on an Applied Biosystems 7900HT realtime PCR system (Applied Biosystems). We made collaboration with the Korean Central Cancer Registry (KCCR) to improve the validity of the mortality data. Total of 3,209 patients were included for survival and recurrence analysis. Results: 492 (15.33%) patients had recurrence. And there were 277 (8.63%) mortalities overall. The median follow-up was for 85.59 month (±29.979). The GG genotype of SNP rs3803662 showed better survival than other AA, AG genotypes (Cumulative survival was 89% vs 84% at 120 months f/u). And it is validated at multivariate analysis (p = 0.024). Conclusion: This study showed strong association between a certain genotype of single SNP and survival of breast cancer patients for the first time. Further lab investigation including functional study or studies on other races should be performed to find a novel or alternative hidden pathways of cancer progression. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-07-09.
Cancer Research | 2013
Mk Kim; H-G Moon; J Kim; Jw Lee; Eunsik Lee; T-K Yoo; D-Y Noh; Wonshik Han
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.
Cancer Research | 2012
J Kim; H-G Moon; Wonshik Han; D-Y Noh
Backgrounds: The issue of whether concomitant ductal carcinoma in situ (DCIS) affects the prognosis of with invasive breast cancer is important but studies of this have reported inconsistent results. So we aimed to assess the character and prognostic difference in infiltrating ductal carcinoma (IDC) according to accompanying DCIS status. Methods: We reviewed the medical records of the patients who underwent surgery for IDC. Male patients, patients who had received neoadjuvant chemotherapy, patients with synchronous bilateral breast cancer, follow-up periods Results: A total of 1751 patients were included, and 1384 patients (79.0%) had concomitant DCIS; 337 had low-grade DCIS, and 1047 patients had high-grade DCIS. The low-grade DCIS group had a significantly lower TNM stage than the high-grade DCIS group. The majority of cases with low-grade DCIS, were ER-positive (85.2%), PR-positive (81.3%) and had low Her-2 (98.7%). When we analyzed the survival rates according to the presence of DCIS, no statistical significance was founded. However, a subgroup analysis showed that the patients with low-grade DCIS survived significantly longer than other patients, whereas those with high-grade DCIS had poorer survival (5 year event-free survival rate; low-grade DCIS vs . without DCIS vs . high-grade DCIS, 97% vs . 93% vs . 86%, p = 0.001). Specially, in patients with lymph node involvement, accompanying high-grade DCIS was independent predictor distant metastasis (HR 5.0, p = 0.026, 95% CI 1.21–20.92). Conclusion: The important factor that affect prognosis of IDC with DCIS is not the presence itself of DCIS component but the grade of DCIS. The patients with low-grade DCIS had a good prognosis and those with high-grade DCIS had a poor prognosis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-35.
Cancer Research | 2012
Jw Lee; H-G Moon; Wonshik Han; D-Y Noh
Backgrounds: Increased expression of HER-2 or amplification of the HER-2/neu gene has been associated with a worse prognosis than with other breast cancer phenotypes. Especially in cases of size of 0.5∼1cm and node-negative status, adjuvant chemotherapy with or without Trastuzumab treatment is suggested by recent National Comprehensive Cancer Network(NCCN) guidelines. In Korea, the breast cancer patient pool is more younger than western data, and there could be some ethnic differences. Methods: The Korean Breast Cancer Society (KBCS) has been collaborating with the Korean Central Cancer Registry (KCCR) to improve the completeness and validity of the breast cancer registry and the mortality data. Data of T1a, bN0M0 breast cancer patients from 1999 to 2006 from KBCS on-line registry was obtained, and a total of 2,962 patients were included for survival analysis. Results: 711 patients (24.0%) was HER-2 positive. Hormone receptor and HER2 status was used to classify 4 molecular subtypes; Hormone receptor(HR)+/HER2−, HR+/HER2+, HR−/HER2+, HR−/HER2−. The median follow-up was for 55.82 month (±24.196). Breast cancer specific survival rate was lowest at HR−/HER2+ subtype(97.9%). It9s 1.0∼1.8% lower than other subtypes. Between all T1N0M0 cases, especially T1b HR−/HER2+ cases showed lowest survival of 96.4%. Conclusion: This study calculated the nationwide survival rates of Korean breast cancer patients with T1a, bN0M0 disease for the first time. HER2 gene positivity was associated with worse prognosis and it9s concordant with western studies. But prognosis of T1N0M0 lesion is much better than that of other nations. So, the usage of chemotherapy and Trastuzumab treatment should be considered more carefully in Korea. Further analysis of the long-term survival and a nationwide collaborative study should be performed to estimate the survival trend of Korean breast cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-23.
Cancer Research | 2012
Mk Kim; D-Y Noh; Wonshik Han; H-G Moon; Sk Ahn; Ji-Won Kim; T. Kim; J Kim; Jw Lee
Background: Breast cancer rarely occurs in very young women(age Patients and Methods: A total of 551 consecutive patients were evaluated, received preoperative chemotherapy and referred to surgery at the Seoul National University Hospital from January 2001 to December 2010. The clinicopathologic factors and the response to neoadjuvant chemotherapy between the very young age group and the older age group were retrospectively compared. A pCR was defined as the absence of residual invasive carcinoma in the breast. Results: Among the 551 patients who received neoadjuvant chemotherapy, 297 patients revealed HR-positive. The median age of all patients was 42 (range, 24∼67)years and very young age group accounted for 17.2%(51/297). Of 297 patients, 262 (88.2%) received taxane-containing regimen pre-operatively, and there9s no difference of chemotherapeutic regimen between two age groups. There were no differences noted between two age groups about clinicopathologic characteristics. The univariate and multivariate analysis of variables related to ORR(CR+PR vs SD+PD) to neoadjuvant chemotherapy showed that very young age at diagnosis was independent predictive factor for poor neoadjuvant chemotherapeutic response.(p = 0.043, OR = 0.528) And this tendency was observed more significantly in age under 30.(p = 0.001, OR = 0.147) Only thirteen patients(4.4%) achieved pCR, which is relatively lower rate, reflective poor chemotherapeutic response in HR-positive group, and there was no relations between pCR rate and the two age groups(p = 0.861) in this study. Taxane-containing regimen(p = 0.004) and Ki67 level(p = 0.005) were related to pCR statistically significantly. Breast conservation rate is not significantly different between two age groups.(age 35= 51.2% vs 41.3%, p = 0.150) Conclusions: The very young age group showed lower ORR(CR+PR) to neoadjuvant chemotherapy, although there was no significant difference in pCR rate between the two age groups in HR-positive breast cancer patients. We might have to consider and revalue the chemotherapeutic role as neoadjuvant therapy in very young age, HR-positive group, since they had lower survival rate than others. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-16.
Cancer Research | 2011
J Kim; Jm You; H-C Shin; Sun Hee Ahn; H-G Moon; Nariya Cho; W-K Moon; Wonshik Han; D-Y Noh
Preoperative breast MRI has been increasingly performed in patients with newly diagnosed breast cancer due to its high sensitivity in assessing the extent and additional malignant foci. But due to it9s low specificity, role of routine preoperative breast MRI has become an issue. In this study we aught to analyze the characteristics of the additional lesion found in preoperative breast MRI and to evaluate the clinicopathological factors in association with likelihood of having additional malignancy. We retrospectively reviewed 2491 patients who undergone surgery due to breast cancer in Seoul National University Hospital(SNUH) between Jan 2006 and Dec 2010. Neoadjuvant chemotherapy cases, patients undergone initial sonography in other center or ones with prior excision were excluded and total 1068 patients were analyzed. The additional lesion was defined as the lesion not found in initial sonography and detected in preoperative breast MRI. The pathology of the additional lesion was reviewed and the association between the clinicopathologic factors and additional malignancy were evaluated. Accuracy of breast MRI was estimated regarding cancer yield, positive predictive value(PPV). Mean age at diagnosis was 50.9 years (21 to 85 years). Overall detection rate of additional lesion was 26.2%(280 out of 1068). Mean size of the additional lesion was 9.8mm(3-51). Additional lesions consist of 99(35.4% of 280) C4 or higher, 174(62.1% of 280) below C4, 7(2.5% of 280) C0 lesions. Among them 100 patients undergone onstage surgery. 5(55% of 100) lesions were in ipsilateral breast and 45(45% of 100) in contralateral breast. Breast conserving surgery and mastectomy rate of the 100 onstage-operation group was 36% versus 64% and 64.6% versus 35.4% in total 1068 patients, showing no significant change of operation method of the primary cancer owing to additional lesion. Among the 100 patients, 54(19.3% of 280) were benign, 3(1.1% of 280) were atypical ductal hyperplasia, 13(4.6% of 280) were in situ carcinoma, 19(6.8% of 280) were invasive carcinoma and 11(3.9% of 280) were unknown. Cancer yield was 2.99%(32 out of 1068) and PPV of preoperative breast MRI was 39.0%(31 out of 82). In univariate analysis, young age and premenopausal patients showed to have higher rate of additional cancer found in MRI(p=0.022, p=0.036). Breast density, size and LN status of the primary cancer didn9t show significancy and neither the hormone receptor status with each p value 0.705, 0.381, 0.973, 0.375 respectively. Lobular carcinoma(ILC or mixed IDC with ILC) and low grade carcinoma showed significancy of having additional malignancy (p=0.019, 0.022). In multivariate analysis age, low grade carcinoma and lobular carcinoma showed independent association with p value 0.014, 0.039, 0.035 respectively(HR 0.95, 95%CI:0.94 o 0.99),(HR 0.39, 95%CI:0.16 to 0.96),(HR 5.66, 95%CI:1.13 to 28.39). Routine preoperative breast MRI use can result in overtreatment also with delay in surgical management. In our data, younger age, low grade carcinoma, lobular carcinoma showed independent association having additional malignant foci in breast MRI. With the basis of mammography and sonography, preoperative breast MRI should only be done when additional gain is considered to overcome the flaws. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-08-12.
Cancer Research | 2011
Sk Ahn; Hyeong-Gon Moon; J Kim; Jm You; H-C Shin; Wonshik Han; D-Y Noh
BACKGROUND: Although chemotherapy and ovarian ablation independently improve the outcome of breast cancer, there is controversy about the benefit of chemotherapy-induced amenorrhea (CIA) in breast cancer. We investigated impact of CIA on response to neoadjuvant chemotherapy in breast cancer patients. METHODS: We reviewed the records of 198 premenopausal patients with breast cancer treated with neoadjuvant chemotherapy between January 2005 and December 2010. Chemotherapy-induced amenorrhea (CIA) was defined as serum FSH level ≥40 IU/L after completion of all scheduled neoadjuvant chemotherapy and prior to definitive surgery. RESULTS: Among 198 breast cancer patients, 132 pts (66.7%) developed CIA after neoadjuvant chemotherapy. 156 pts (78%) underwent DA chemotherapy. The age of CIA patients was older than non-CIA patients (41.55±5.55 years vs. 38.27 ± 6.86 years, p=0.001). The incidence of CIA after neoadjuvant chemotherapy was significantly higher in responder group (responder vs. nonresponder: 87 pts (74.4%) vs. 45 pts (55.6%); p=0.006). Additionally, FSH level after all scheduled neoadjuvant chemotherapy was significantly higher in responder group (FSH 56.41±32.41 IU/L vs. 45.76±30.31 IU/L; p=0.021). In univariate analysis, CIA (p=0.006) and total number of chemotherapy cycle regardless of chemotherapy regimen (p=0.04) were significantly associated with tumor response. CIA was only independent factor for tumor response after neoadjuvant chemotherapy on multivariate analysis (p=0.012). CONCLUSION: CIA after neoadjuvant chemotherapy was significantly associated with response to neoadjuvant chemotherapy in locally advanced breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-19.