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Original Articles
Ten-Year Follow-Up Clinical Outcomes and the Role of Adjuvant Chemotherapy in HER2-Positive Patients with Microinvasive Breast Cancer
Yeokyeong Shin, Soo-Young Lee, Hyehyun Jeong, Jin-Hee Ahn, Kyung Hae Jung, Sung-Bae Kim, Hee Jeong Kim, Jong Won Lee, Byung Ho Son, BeomSeok Ko, Ji Sun Kim, Il Yong Chung, Hee Jin Lee, Gyungyub Gong, Sae Byul Lee, Jae Ho Jeong
Received November 22, 2024  Accepted March 3, 2025  Published online March 5, 2025  
DOI: https://doi.org/10.4143/crt.2024.1120    [Accepted]
AbstractAbstract PDF
Purpose
Although HER2 positivity is prevalent in microinvasive breast cancer (MIBC), data focused on HER2-positive MIBC are limited. We investigated the clinical course and long-term outcomes of HER2-positive MIBC and evaluated the role of adjuvant chemotherapy.
Materials and Methods
The study included patients with curatively resected pT1mi pN0 HER2-positive breast cancer between January 2000 and January 2020. Treatments and survival outcomes, including invasive breast cancer-free survival (IBCFS), distant recurrence-free survival (DRFS), and overall survival (OS) were analyzed.
Results
The analysis included 799 female patients. The median age was 51 years (range, 23–79), and 51.6% (n=412) were premenopausal. Multifocality was confirmed in 17.3% (n=138), and estrogen receptor (ER) positivity in 29.8% (n = 238). Adjuvant chemotherapy was administered to 17.5% (n=140), with doxifluridine in 96.4% of cases. One patient (0.1%) received trastuzumab. With a median follow-up of 119.0 months (95% CI, 114.0–127.0), the 8-year IBCFS, DRFS, and OS were 91.2% (95% CI, 89.1–93.3), 97.5% (95% CI, 96.4–98.7), and 98.8% (95% CI, 98.0–99.6), respectively. No significant differences were observed between patients with and without adjuvant chemotherapy. The lack of differences in IBCFS by chemotherapy was consistent across subgroups, including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative disease.
Conclusion
A clinically meaningful proportion of HER2-positive MIBC patients experience IBCFS events with long-term follow-up. Adjuvant chemotherapy did not improve survival, potentially due to the use of an outdated, ineffective regimen. The role of modern adjuvant regimens, particularly those incorporating HER2-targeted therapy, warrants further exploration.
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Prognostic Performance of the Next-Generation Sequencing-Based Multigene Assay in Early Breast Cancer Patients Treated According to the 21-Gene Assay Results
Eunhye Kang, Jong-Ho Cheun, Jeeyeon Lee, Jiwon Koh, Hyunwoo Lee, Ji-Young Park, Hee Jin Lee, Byeongju Kang, Woong Ki Park, Jeongeun Son, Bumjoon Kim, Woosung Chung, Wonshik Han, Han-Byoel Lee, Sae Byul Lee, Jai Min Ryu
Received October 28, 2024  Accepted December 22, 2024  Published online December 23, 2024  
DOI: https://doi.org/10.4143/crt.2024.1035    [Epub ahead of print]
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Multigene assays guide treatment decisions in early-stage hormone receptor-positive breast cancer. OncoFREE, a next-generation sequencing assay using 179 genes, was developed for this purpose. This study aimed to evaluate the concordance between the Oncotype DX (ODX) recurrence score (RS) and the OncoFREE Decision Index (DI) and to compare their performance.
Materials and Methods
We retrospectively collected tumor blocks from patients who underwent ODX and treatment between 2012 and 2022 at four tertiary hospitals and performed OncoFREE on these samples. Distant metastasis-free survival (DMFS) was compared using RS and DI, with score cut-offs of 25 and 20, respectively.
Results
Among 838 patients, a strong correlation was observed between RS and DI (Pearson correlation coefficient 0.83). At a median follow-up of 54 months, patients with high DI had significantly worse DMFS compared to those with low-DI (log-rank p < 0.001; hazard ratio [HR], 5.73; 95% confidence interval [CI], 1.87 to 17.57; multivariable p=0.048; HR, 3.45; 95% CI, 1.01 to 11.76). In 513 patients aged ≤ 50 years, DMFS was significantly different as a function of DI (p=0.035; HR, 3.98; 95% CI, 1.00 to 15.89) but not RS (p=0.792). Among 376 patients aged ≤ 50 years who avoided chemotherapy based on low-RS, 64 with high DI had worse DMFS (p=0.015; HR, 5.91; 95% CI, 1.17 to 29.78).
Conclusion
OncoFREE showed strong concordance with ODX and effectively identified high-risk patients, particularly in younger individuals. It could be an affordable alternative to ODX for guiding treatment in hormone receptor-positive early breast cancer.
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Breast cancer
Implementation of BRCA Test among Young Breast Cancer Patients in South Korea: A Nationwide Cohort Study
Yung-Huyn Hwang, Tae-Kyung Yoo, Sae Byul Lee, Jisun Kim, Beom Seok Ko, Hee Jeong Kim, Jong Won Lee, Byung Ho Son, Il Yong Chung
Cancer Res Treat. 2024;56(3):802-808.   Published online February 19, 2024
DOI: https://doi.org/10.4143/crt.2023.1186
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to investigate the frequency of BRCA testing and related factors among young breast cancer patients (age < 40 years) in South Korea.
Materials and Methods
We conducted a nationwide retrospective cohort study using data from the Health Insurance Review and Assessment claims. Newly diagnosed breast cancer patients younger than 40 were included. Annual BRCA testing ratios (number of BRCA test recipients/the number of patients undergoing breast cancer surgery in each year) were analyzed by region and health care delivery system. We investigated the location of breast cancer diagnosis and BRCA testing.
Results
From January 2010 to December 2020, there were 25,665 newly diagnosed young breast cancer patients, of whom 12,186 (47.5%) underwent BRCA testing. The BRCA testing ratios increased gradually from 0.084 (154/1,842) in 2010 to 0.961 (1,975/2,055) in 2020. Medical aid (vs. health insurance) and undergoing surgery in metropolitan cities or others (vs. Seoul), general hospitals, and clinics (vs. tertiary hospitals) were associated with a lower likelihood of BRCA testing. While 97.8% of the patients diagnosed in Seoul underwent BRCA testing in Seoul, 22.9% and 29.2% of patients who were diagnosed in metropolitan areas and other regions moved to Seoul and underwent BRCA testing, respectively.
Conclusion
The frequency of BRCA testing has increased over time in South Korea, with Seoul showing a particularly high rate of testing. About one-quarter of patients diagnosed with breast cancer outside of Seoul moved to Seoul and underwent BRCA testing.
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A Nomogram for Predicting the Oncotype DX Recurrence Score in Women with T1-3N0-1miM0 Hormone Receptor‒Positive, Human Epidermal Growth Factor 2 (HER2)‒Negative Breast Cancer
Sae Byul Lee, Junetae Kim, Guiyun Sohn, Jisun Kim, Il Yong Chung, Hee Jeong Kim, Beom Seok Ko, Byung Ho Son, Sei-Hyun Ahn, Jong Won Lee, Kyung Hae Jung
Cancer Res Treat. 2019;51(3):1073-1085.   Published online November 1, 2018
DOI: https://doi.org/10.4143/crt.2018.357
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This preliminary study was conducted to evaluate the association between Oncotype DX (ODX) recurrence score and traditional prognostic factors. We also developed a nomogram to predict subgroups with low ODX recurrence scores (less than 25) and to avoid additional chemotherapy treatments for those patients.
Materials and Methods
Clinicopathological and immunohistochemical variables were retrospectively retrieved and analyzed from a series of 485 T1-3N0-1miM0 hormone receptor-positive, human epidermal growth factor 2‒negative breast cancer patients with available ODX test results at Asan Medical Center from 2010 to 2016. One hundred twenty-seven patients (26%) had positive axillary lymph node micrometastases, and 408 (84%) had ODX recurrence scores of ≤25. Logistic regression was performed to build a nomogram for predicting a low-risk subgroup of the ODX assay.
Results
Multivariate analysis revealed that estrogen receptor (ER) score, progesterone receptor (PR) score, histologic grade, lymphovascular invasion (LVI), and Ki-67 had a statistically significant association with the low-risk subgroup. With these variables, we developed a nomogram to predict the low-risk subgroup with ODX recurrence scores of ≤25. The area under the receiver operating characteristic curve was 0.90 (95% confidence interval [CI], 0.85 to 0.96). When applied to the validation group the nomogram was accurate with an area under the curve = 0.88 (95% CI, 0.83 to 0.95).
Conclusion
The low ODX recurrence score subgroup can be predicted by a nomogram incorporating five traditional prognostic factors: ER, PR, histologic grade, LVI, and Ki-67. Our nomogram, which predicts a low-risk ODX recurrence score, will be a useful tool to help select patients who may or may not need additional ODX testing.

Citations

Citations to this article as recorded by  
  • A Novel Nomogram for Estimating a High-Risk Result in the EndoPredict® Test for Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Carcinoma
    Víctor Macarrón, Itsaso Losantos-García, Alberto Peláez-García, Laura Yébenes, Alberto Berjón, Laura Frías, Covadonga Martí, Pilar Zamora, José Ignacio Sánchez-Méndez, David Hardisson
    Cancers.2025; 17(2): 273.     CrossRef
  • Nomogram Development for Assessing Oncotype DX Recurrence Scores in Breast Cancer: A Chinese Population Study
    Jiayin Song, Lin Yang, Zhengqi Feng, Liyu Jiang
    Cancer Medicine.2025;[Epub]     CrossRef
  • Efficacy, safety, and predictive model of Palbociclib in the treatment of HR-positive and HER2-negative metastatic breast cancer
    Wei Wang, Wenqian Lei, Ziru Fang, Ruiyuan Jiang, Xiaojia Wang
    BMC Cancer.2024;[Epub]     CrossRef
  • Development and validation of a clinical breast cancer tool for accurate prediction of recurrence
    Asim Dhungana, Augustin Vannier, Fangyuan Zhao, Jincong Q. Freeman, Poornima Saha, Megan Sullivan, Katharine Yao, Elbio M. Flores, Olufunmilayo I. Olopade, Alexander T. Pearson, Dezheng Huo, Frederick M. Howard
    npj Breast Cancer.2024;[Epub]     CrossRef
  • Prediction of Oncotype DX Recurrence Score Based on Systematic Evaluation of Ki-67 Scores in Hormone Receptor-Positive Early Breast Cancer
    Ji Min Kim, Eun Yoon Cho
    Journal of Breast Cancer.2024; 27(3): 201.     CrossRef
  • Development of a nomogram to predict recurrence scores obtained using Oncotype DX in Japanese patients with breast cancer
    Akio Shibata, Nobuko Tamura, Keiichi Kinowaki, Aya Nishikawa, Kiyo Tanaka, Yoko Kobayashi, Takuya Ogura, Yuko Tanabe, Hidetaka Kawabata
    Breast Cancer.2024; 31(6): 1018.     CrossRef
  • Shear-wave elastography-based nomograms predicting 21-gene recurrence score for adjuvant chemotherapy decisions in patients with breast cancer
    Ji Hyun Youk, Eun Ju Son, Joon Jeong, Hye Mi Gweon, Na Lae Eun, Jeong-Ah Kim
    European Journal of Radiology.2023; 158: 110638.     CrossRef
  • Prediction of Oncotype DX Recurrence Score Using Clinicopathological Variables in Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer
    Min Chong Kim, Sun Young Kwon, Jung Eun Choi, Su Hwan Kang, Young Kyung Bae
    Journal of Breast Cancer.2023; 26(2): 105.     CrossRef
  • Clinicopathological Factors Associated with Oncotype DX Risk Group in Patients with ER+/HER2- Breast Cancer
    Ran Song, Dong-Eun Lee, Eun-Gyeong Lee, Seeyoun Lee, Han-Sung Kang, Jai Hong Han, Keun Seok Lee, Sung Hoon Sim, Heejung Chae, Youngmee Kwon, Jaeyeon Woo, So-Youn Jung
    Cancers.2023; 15(18): 4451.     CrossRef
  • A simplified risk scoring system for predicting high-risk groups in gene expression tests for patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and node-positive breast cancer
    Kwang Hyun Yoon, Suk Jun Lee, Yujin Kim, Jee Hyun Ahn, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Seho Park
    Annals of Surgical Treatment and Research.2023; 105(6): 360.     CrossRef
  • Deep Learning-Based Pathology Image Analysis Enhances Magee Feature Correlation With Oncotype DX Breast Recurrence Score
    Hongxiao Li, Jigang Wang, Zaibo Li, Melad Dababneh, Fusheng Wang, Peng Zhao, Geoffrey H. Smith, George Teodoro, Meijie Li, Jun Kong, Xiaoxian Li
    Frontiers in Medicine.2022;[Epub]     CrossRef
  • A Novel Surrogate Nomogram Capable of Predicting OncotypeDX Recurrence Score©
    Matthew G. Davey, Amirhossein Jalali, Éanna J. Ryan, Ray P. McLaughlin, Karl J. Sweeney, Michael K. Barry, Carmel M. Malone, Maccon M. Keane, Aoife J. Lowery, Nicola Miller, Michael J. Kerin
    Journal of Personalized Medicine.2022; 12(7): 1117.     CrossRef
  • Use of a supervised machine learning model to predict Oncotype DX risk category in node-positive patients older than 50 years of age
    Austin D. Williams, Kate R. Pawloski, Hannah Y. Wen, Varadan Sevilimedu, Donna Thompson, Monica Morrow, Mahmoud El-Tamer
    Breast Cancer Research and Treatment.2022; 196(3): 565.     CrossRef
  • The Role of Oncotype DX® Recurrence Score in Predicting Axillary Response After Neoadjuvant Chemotherapy in Breast Cancer
    Jaime A. Pardo, Betty Fan, Alessandra Mele, Stephanie Serres, Monica G. Valero, Isha Emhoff, Amulya Alapati, Ted A. James
    Annals of Surgical Oncology.2021; 28(3): 1320.     CrossRef
  • A nomogram to predict the high-risk RS in HR+/HER2-breast cancer patients older than 50 years of age
    Jing Yu, Jiayi Wu, Ou Huang, Jianrong He, Li Zhu, Weiguo Chen, Yafen Li, Xiaosong Chen, Kunwei Shen
    Journal of Translational Medicine.2021;[Epub]     CrossRef
  • Clinicopathological correlates, oncological impact, and validation of Oncotype DX™ in a European Tertiary Referral Centre
    Matthew G. Davey, Éanna J. Ryan, Sami Abd Elwahab, Jessie A. Elliott, Peter F. McAnena, Karl J. Sweeney, Carmel M. Malone, Ray McLaughlin, Michael K. Barry, Maccon M. Keane, Aoife J. Lowery, Michael J. Kerin
    The Breast Journal.2021; 27(6): 521.     CrossRef
  • Dynamic contrast enhanced-MRI and diffusion-weighted image as predictors of lymphovascular invasion in node-negative invasive breast cancer
    Bo Bae Choi
    World Journal of Surgical Oncology.2021;[Epub]     CrossRef
  • Prognostic value of the 21-gene recurrence score for regional recurrence in patients with estrogen receptor-positive breast cancer
    Minji Koh, Jinhong Jung, Su Ssan Kim, Seung Do Ahn, Eun Kyung Choi, Il Yong Chung, Jong Won Lee, Sung-Bae Kim, Jae Ho Jeong
    Breast Cancer Research and Treatment.2021; 188(3): 583.     CrossRef
  • A nomogram for predicting probability of low risk of MammaPrint results in women with clinically high-risk breast cancer
    Young Joo Lee, Young Sol Hwang, Junetae Kim, Sei-Hyun Ahn, Byung Ho Son, Hee Jeong Kim, Beom Seok Ko, Jisun Kim, Il Yong Chung, Jong Won Lee, Sae Byul Lee
    Scientific Reports.2021;[Epub]     CrossRef
  • Development of a Nomogram to Predict the Recurrence Score of 21-Gene Prediction Assay in Hormone Receptor–Positive Early Breast Cancer
    Shin Hye Yoo, Tae-Yong Kim, Miso Kim, Kyung-Hun Lee, Eunshin Lee, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han, Dong-Young Noh, Sae-Won Han, Tae-You Kim, Seock-Ah Im
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No Association of Positive Superficial and/or Deep Margins with Local Recurrence in Invasive Breast Cancer Treated with Breast-Conserving Surgery
Tae In Yoon, Jong Won Lee, Sae Byul Lee, Guiyun Sohn, Jisun Kim, Il Young Chung, Hee Jeong Kim, Beom Seok Ko, Byung Ho Son, Gyungyub Gong, Sung-Bae Kim, Su Ssan Kim, Seung Do Ahn, Minsung Chung, Sei Hyun Ahn
Cancer Res Treat. 2018;50(1):275-282.   Published online April 14, 2017
DOI: https://doi.org/10.4143/crt.2017.041
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We evaluated the effect of positive superficial and/or deep margin status on local recurrence (LR) in invasive breast cancer treated with breast-conserving surgery (BCS) followed by radiotherapy.
Materials and Methods
In total, 3,403 stage 1 and 2 invasive breast cancer patients treated with BCS followed by radiotherapy from January 2000 to December 2008 were included in this study. These patients were divided into three groups according to margin status: clear resection margin status for all sections (group 1, n=3,195); positive margin status in superficial and/or deep sections (group 2, n=121); and positive peripheral parenchymal margin regardless of superficial and/or deep margin involvement (group 3, n=87). The LR-free survival between these three groups was compared and the prognostic role of margin status was analyzed.
Results
Across all groups, age, tumor size, nodal status, and human epidermal growth factor receptor 2 status did not significantly differ. High grade, positive extensive intraductal component, hormone receptor positivity, hormone therapy received, and chemotherapy not received were more prevalent in groups 2 and 3 than in group 1. Five-year LR rates in groups 1, 2, and 3 were 1.9%, 1.7%, and 7.7%, respectively. Multivariate analysis revealed that group 3 was a significant predictor for LR (hazard ratio [HR], 4.78; p < 0.001), but that positive superficial and/or deep margin was not (HR, 0.66; p=0.57).
Conclusion
Superficial and/or deep margin involvement following BCS is not an important predictor for LR.

Citations

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  • Locoregional Recurrence-Free Survival in Postmastectomy Breast Cancer: A Comparative Longitudinal Study of Hypofractionated Versus Conventional Fractionated Radiation Therapy
    Suma Susan Meloot, Ciniraj Raveendran, IP Yadev
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    Seok-Joo Chun, Ji Hwan Jo, Yong Bae Kim, Sangjoon Park, Sung-Ja Ahn, Su Ssan Kim, Kyubo Kim, Kyung Hwan Shin
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  • Comparison of Recurrence Rate Between Re-Excision With Radiotherapy and Radiotherapy-Only Groups in Surgical Margin Involvement of In Situ Carcinoma
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  • 13 Web of Science
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Survival Outcome of Combined GnRH Agonist and Tamoxifen Is Comparable to That of Sequential Adriamycin and Cyclophosphamide Chemotherapy Plus Tamoxifen in Premenopausal Patients with Lymph-Node–Negative, Hormone-Responsive, HER2-Negative, T1-T2 Breast Cancer
Guiyun Sohn, Sei Hyun Ahn, Hee Jeong Kim, Byung-Ho Son, Jong Won Lee, Beom Seok Ko, Yura Lee, Sae Byul Lee, Seunghee Baek
Cancer Res Treat. 2016;48(4):1351-1362.   Published online April 6, 2016
DOI: https://doi.org/10.4143/crt.2015.444
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to compare treatment outcomes between combined gonadotropin-releasing hormone agonist and tamoxifen (GnRHa+T) and sequential adriamycin and cyclophosphamide chemotherapy and tamoxifen (AC->T) in premenopausal patients with hormone-responsive, lymph-node–negative breast cancer.
Materials and Methods
In total, 994 premenopausal women with T1-T2, lymph-node–negative, hormone-receptor-positive, HER2-negative breast cancer between January 2003 and December 2008 were included in this retrospective cohort study. GnRHa+T and AC->T were administered to 608 patients (61.2%) and 386 patients (38.8%), respectively. Propensity score matching and inverse probability weighting were applied to the original cohort, and 260 patients for each treatment arm were included in the final analysis. Recurrence-free, cancer-specific, and overall survival was compared between the two treatment groups.
Results
A total of 994 patients were followed up for a median of 7.4 years (range, 0.5 to 11.4 years). The 5-year follow-up rate was 98.7%, and 13 patients were lost to follow-up. In propensity=matched cohorts (n=520), there was no difference in recurrence-free, cancer-specific, and overall survival rates between the two treatment groups (p=0.306, p=0.212, and p=0.102, respectively), and this was maintained after applying inverse probability weighting.
Conclusion
GnRHa+T is a reasonable alternative to AC-> T in patients with premenopausal, hormoneresponsive, HER2-negative, lymph-node–negative, T1-T2 breast cancer.

Citations

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  • Effectiveness of post-mastectomy adjuvant chemotherapy for the treatment of patients with prognostic stage IB breast cancer: A SEER-based study
    HongMei Wang, Yi Peng, Jianbin Wu, ZhuangWei Chen, HuaLe Zhang
    Asian Journal of Surgery.2023; 46(9): 3634.     CrossRef
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    Elizabeth M. Salvo, Abril Oliva Ramirez, Jenilee Cueto, Ernest H. Law, Aaron Situ, Chris Cameron, Imtiaz A. Samjoo
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    Zhen-Yu Wu, Young-jin Lee, Heejeong Kim, Jongwon Lee, Il Yong Chung, Jisun Kim, Saebyeol Lee, Byung-Ho Son, Sung-Bae Kim, Jae Ho Jeong, Gyungyub Gong, Sei-Hyun Ahn, BeomSeok Ko
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • Changes in bone mineral density during 5 years of adjuvant treatment in premenopausal breast cancer patients
    Minsung Kim, Hanna Kim, Sei Hyun Ahn, Vafa Tabatabaie, Sung Wook Choi, Guiyun Sohn, Sae Byul Lee, Beom Seok Ko, Il Yong Chung, Jisun Kim, Jong Won Lee, Byung Ho Son, Hee Jeong Kim
    Breast Cancer Research and Treatment.2020; 180(3): 657.     CrossRef
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    Young-jin Lee, Zhen-Yu Wu, Hee jeong Kim, Jong Won Lee, Il Yong Chung, Jisun Kim, Sae Byul Lee, Byung Ho Son, Sung-Bae Kim, Jae Ho Jung, Gyungyub Gong, Sei-Hyun Ahn, BeomSeok Ko
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    Molecular and Clinical Oncology.2019;[Epub]     CrossRef
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