1.A 10-Gene Signature to Predict the Prognosis of Early-Stage Triple-Negative Breast Cancer
Chang Min KIM ; Kyong Hwa PARK ; Yun Suk YU ; Ju Won KIM ; Jin Young PARK ; Kyunghee PARK ; Jong-Han YU ; Jeong Eon LEE ; Sung Hoon SIM ; Bo Kyoung SEO ; Jin Kyeoung KIM ; Eun Sook LEE ; Yeon Hee PARK ; Sun-Young KONG
Cancer Research and Treatment 2024;56(4):1113-1125
Purpose:
Triple-negative breast cancer (TNBC) is a particularly challenging subtype of breast cancer, with a poorer prognosis compared to other subtypes. Unfortunately, unlike luminal-type cancers, there is no validated biomarker to predict the prognosis of patients with early-stage TNBC. Accurate biomarkers are needed to establish effective therapeutic strategies.
Materials and Methods:
In this study, we analyzed gene expression profiles of tumor samples from 184 TNBC patients (training cohort, n=76; validation cohort, n=108) using RNA sequencing.
Results:
By combining weighted gene expression, we identified a 10-gene signature (DGKH, GADD45B, KLF7, LYST, NR6A1, PYCARD, ROBO1, SLC22A20P, SLC24A3, and SLC45A4) that stratified patients by risk score with high sensitivity (92.31%), specificity (92.06%), and accuracy (92.11%) for invasive disease-free survival. The 10-gene signature was validated in a separate institution cohort and supported by meta-analysis for biological relevance to well-known driving pathways in TNBC. Furthermore, the 10-gene signature was the only independent factor for invasive disease-free survival in multivariate analysis when compared to other potential biomarkers of TNBC molecular subtypes and T-cell receptor β diversity. 10-gene signature also further categorized patients classified as molecular subtypes according to risk scores.
Conclusion
Our novel findings may help address the prognostic challenges in TNBC and the 10-gene signature could serve as a novel biomarker for risk-based patient care.
2.Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach
Tae-Han KIM ; In-Ho KIM ; Seung Joo KANG ; Miyoung CHOI ; Baek-Hui KIM ; Bang Wool EOM ; Bum Jun KIM ; Byung-Hoon MIN ; Chang In CHOI ; Cheol Min SHIN ; Chung Hyun TAE ; Chung sik GONG ; Dong Jin KIM ; Arthur Eung-Hyuck CHO ; Eun Jeong GONG ; Geum Jong SONG ; Hyeon-Su IM ; Hye Seong AHN ; Hyun LIM ; Hyung-Don KIM ; Jae-Joon KIM ; Jeong Il YU ; Jeong Won LEE ; Ji Yeon PARK ; Jwa Hoon KIM ; Kyoung Doo SONG ; Minkyu JUNG ; Mi Ran JUNG ; Sang-Yong SON ; Shin-Hoo PARK ; Soo Jin KIM ; Sung Hak LEE ; Tae-Yong KIM ; Woo Kyun BAE ; Woong Sub KOOM ; Yeseob JEE ; Yoo Min KIM ; Yoonjin KWAK ; Young Suk PARK ; Hye Sook HAN ; Su Youn NAM ; Seong-Ho KONG ;
Journal of Gastric Cancer 2023;23(1):3-106
Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.
3.Erratum: Korean Practice Guidelines for Gastric Cancer 2022: An Evidencebased, Multidisciplinary Approach
Tae-Han KIM ; In-Ho KIM ; Seung Joo KANG ; Miyoung CHOI ; Baek-Hui KIM ; Bang Wool EOM ; Bum Jun KIM ; Byung-Hoon MIN ; Chang In CHOI ; Cheol Min SHIN ; Chung Hyun TAE ; Chung sik GONG ; Dong Jin KIM ; Arthur Eung-Hyuck CHO ; Eun Jeong GONG ; Geum Jong SONG ; Hyeon-Su IM ; Hye Seong AHN ; Hyun LIM ; Hyung-Don KIM ; Jae-Joon KIM ; Jeong Il YU ; Jeong Won LEE ; Ji Yeon PARK ; Jwa Hoon KIM ; Kyoung Doo SONG ; Minkyu JUNG ; Mi Ran JUNG ; Sang-Yong SON ; Shin-Hoo PARK ; Soo Jin KIM ; Sung Hak LEE ; Tae-Yong KIM ; Woo Kyun BAE ; Woong Sub KOOM ; Yeseob JEE ; Yoo Min KIM ; Yoonjin KWAK ; Young Suk PARK ; Hye Sook HAN ; Su Youn NAM ; Seong-Ho KONG
Journal of Gastric Cancer 2023;23(2):365-373
5.Prediction of Cancer Incidence and Mortality in Korea, 2020
Kyu-Won JUNG ; Young-Joo WON ; Seri HONG ; Hyun-Joo KONG ; Eun Sook LEE
Cancer Research and Treatment 2020;52(2):351-358
Purpose:
This study aimed to report the projected cancer incidence and mortality for the year 2020to estimate Korea’s current cancer burden.
Materials and Methods:
Cancer incidence data from 1999 to 2017 were obtained from the Korea National CancerIncidence Database, and cancer mortality data from 1993 to 2018 were acquired from StatisticsKorea. Cancer incidence and mortality were projected by fitting a linear regressionmodel to observed age-specific cancer rates against observed years and then by multiplyingthe projected age-specific rates by the age-specific population. A Joinpoint regression modelwas used to determine the year in which the linear trend changed significantly; we only usedthe data of the latest trend.
Results:
In total, 243,263 new cancer cases and 80,546 cancer deaths are expected to occur inKorea in 2020. The most common cancer site is expected to be the lung, followed by thestomach, thyroid, colon/rectum, and breast. These five cancers types are expected to representhalf of the overall burden of cancer in Korea. The most common type of canceramong people who die is expected to be lung cancer, followed by liver, colon/rectal, pancreatic,and stomach cancers.
Conclusion
The incidence rates for all types of cancer in Korea are estimated to decrease gradually.These up-to-date estimates of the cancer burden in Korea could be an important resourcefor planning and evaluating cancer-control programs.
6.Outcomes of Pregnancy after Breast Cancer in Korean Women:A Large Cohort Study
Moo Hyun LEE ; Young Ae KIM ; Jin Hyuk HONG ; So-Youn JUNG ; Sunmi LEE ; Sun-Young KONG ; Boyoung PARK ; Eun Sook LEE
Cancer Research and Treatment 2020;52(2):426-437
Purpose:
The purpose of this study was to determine the rate and outcomes of pregnancies subsequentto breast cancer in Korea, and the effect of such pregnancies on the prognosis ofwomen who survived breast cancer and subsequently conceived.
Materials and Methods:
We followed a total of 31,761 Korean women 45 years of age or younger who were treatedfor primary breast cancer from 2002 to 2010. We also included follow-up surveys that wereconducted through December 2011. We identified recurrence and mortality from breastcancer using data linked to the Korea National Health Insurance database. We used propensityscore matching of the study cohort to analyze the risks of recurrence and mortality frombreast cancer depending on pregnancy.
Results:
Within our sample, 992 women (3.1%) became pregnant after receiving treatment for breastcancer. Of those, 622 (67.5%) successfully delivered; the remaining 370 (32.5%) failed todeliver. After propensity score matching, we found that the women who became pregnantafter breast cancer did not have a different risk of recurrence (hazard ratio [HR], 0.503;95% confidence interval [CI], 0.434 to 0.584) and death (HR, 0.520; 95% CI, 0.397 to0.681), compared with those who did not conceive after breast cancer treatment.
Conclusion
Our study is the first to report outcomes for Korean women who survived breast cancer andsubsequently conceived. Women who survived breast cancer and subsequently becamepregnant did not show a poorer survival outcome, compared with those who did not becomepregnant.
7.Cancer Statistics in Korea: Incidence, Mortality, Survival, andPrevalence in 2017
Seri HONG ; Young-Joo WON ; Young Ran PARK ; Kyu-Won JUNG ; Hyun-Joo KONG ; Eun Sook LEE ; ;
Cancer Research and Treatment 2020;52(2):335-350
Purpose:
This study reports the cancer statistics and temporal trends in Korea on a nationwide scale,including incidence, survival, prevalence, and mortality in 2017.
Materials and Methods:
The incidence, survival, and prevalence rates of cancer were evaluated using data from theKorea National Cancer Incidence Database from 1999 to 2017 with follow-up until December31, 2018. Deaths from cancer were assessed using cause-of-death data from 1983 to2017, obtained from Statistics Korea. Crude and age-standardized rates (ASRs) for incidence,mortality, and prevalence, and 5-year relative survival rates were calculated andtrend analysis was performed.
Results:
In 2017, newly diagnosed cancer cases and deaths from cancer numbered 232,255 (ASR,264.4 per 100,000) and 78,863 (ASR, 76.6 per 100,000), respectively. The overall cancerincidence rates increased annually by 3.5% from 1999 to 2011 and decreased by 2.7%annually thereafter. Cancer mortality rates have been decreasing since 2002, by 2.8%annually. The 5-year relative survival rate for all patients diagnosed with cancer between2013 and 2017 was 70.4%, which contributed to a prevalence of approximately 1.87 millioncases by the end of 2017.
Conclusion
The burden of cancer measured by incidence and mortality rates have improved in Korea,with the exception of a few particular cancers that are associated with increasing incidenceor mortality rates. However, cancer prevalence is increasing rapidly, with the dramaticimprovement in survival during the past several years. Comprehensive cancer control strategiesand efforts should continue, based on the changes of cancer statistics.
8.Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test
Hee-Chul SHIN ; Han-Byoel LEE ; Tae-Kyung YOO ; Eun-Shin LEE ; Ryong Nam KIM ; Boyoung PARK ; Kyong-Ah YOON ; Charny PARK ; Eun Sook LEE ; Hyeong-Gon MOON ; Dong-Young NOH ; Sun-Young KONG ; Wonshik HAN
Cancer Research and Treatment 2020;52(3):697-713
Purpose:
Hereditary cancer syndrome means that inherited genetic mutations can increase a person's risk of developing cancer. We assessed the frequency of germline mutations using an nextgeneration sequencing (NGS)–based multiple-gene panel containing 64 cancer-predisposing genes in Korean breast cancer patients with clinical features of hereditary breast and ovarian cancer syndrome (HBOC).
Materials and Methods:
A total of 64 genes associated with hereditary cancer syndrome were selected for development of an NGS-based multi-gene panel. Targeted sequencing using the multi-gene panel was performed to identify germline mutations in 496 breast cancer patients with clinical features of HBOC who underwent breast cancer surgery between January 2002 and December 2017.
Results:
Of 496 patients, 95 patients (19.2%) were found to have 48 deleterious germline mutations in 16 cancer susceptibility genes. The deleterious mutations were found in 39 of 250 patients (15.6%) who had breast cancer and another primary cancer, 38 of 169 patients (22.5%) who had a family history of breast cancer (≥ 2 relatives), 16 of 57 patients (28.1%) who had bilateral breast cancer, and 29 of 84 patients (34.5%) who were diagnosed with breast cancer at younger than 40 years of age. Of the 95 patients with deleterious mutations, 60 patients (63.2%) had BRCA1/2 mutations and 38 patients (40.0%) had non-BRCA1/2 mutations. We detected two novel deleterious mutations in BRCA2 and MLH1.
Conclusion
NGS-based multiple-gene panel testing improved the detection rates of deleterious mutations and provided a cost-effective cancer risk assessment.
9.Interaction Effect Between Breast Density and Reproductive Factors on Breast Cancer Risk in Korean Population
Se Eun LIM ; HyoJin AHN ; Eun Sook LEE ; Sun Young KONG ; So Youn JUNG ; Seeyoun LEE ; Han Sung KANG ; Eun Gyeong LEE ; Jai Hong HAN ; Boyoung PARK
Journal of Cancer Prevention 2019;24(1):26-32
BACKGROUND: This study was conducted to explore the effect of known risk factors, focusing on risk factors including age at menarche, age at menopause, number of children, family history of breast cancer, and age at first birth according to breast density, in consideration of interaction among East-Asian women. METHODS: Case-control study with 2,123 cases and 2,121 controls with mammographic density was conducted. Using the mammographic film, breast density was measured using Breast Imaging-Reporting and Data System. To identify the association of selected reproductive factors including age at menarche, age at menopause, number of children, family history of breast cancer, and age at first birth according to breast density, stratified analysis was conducted according to breast density groups and interaction effects was assessed. The results were presented with adjusted OR and 95% CIs. RESULTS: Significant interaction effect between age at first birth and breast density on breast cancer (P = 0.048) was observed. Women with age at first birth ≥ 28 years old showed increased breast cancer risk in extremely dense breast group (≥ 75%) (OR = 1.627, 95% CI = 1.190–2.226). However, women with fatty breast (< 50%) and heterogeneously dense breast (50%–75%) did not show an increased association. Age at menarche, age at menopause, number of children, and family history of breast cancer did not show significant interaction with breast cancer and similar risk patterns were observed. CONCLUSIONS: Age at first birth showed significant interaction with breast density on breast cancer risk. Further studies considering biologically plausable model between exposure, intermediate outcomes and breast cancer risk with prospective design need to be undertaken in East Asian women.
Asian Continental Ancestry Group
;
Birth Order
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Breast Neoplasms
;
Breast
;
Case-Control Studies
;
Child
;
Female
;
Humans
;
Information Systems
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Menarche
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Menopause
;
Prospective Studies
;
Reproductive History
;
Risk Factors
10.Different Patterns of Risk Reducing Decisions in Affected or Unaffected BRCA Pathogenic Variant Carriers.
Eun Gyeong LEE ; Hyok Jo KANG ; Myong Cheol LIM ; Boyoung PARK ; Soo Jin PARK ; So Youn JUNG ; Seeyoun LEE ; Han Sung KANG ; Sang Yoon PARK ; Boram PARK ; Jungnam JOO ; Jai Hong HAN ; Sun Young KONG ; Eun Sook LEE
Cancer Research and Treatment 2019;51(1):280-288
PURPOSE: The purpose of this study was to investigate decision patterns to reduce the risks of BRCArelated breast and gynecologic cancers in carriers of BRCA pathogenic variants. We found a change in risk-reducing (RR) management patterns after December 2012, when the National Health Insurance System (NHIS) of Korea began to pay for BRCA testing and riskreducing salpingo-oophorectomy (RRSO) in pathogenic-variant carriers. MATERIALS AND METHODS: The study group consisted of 992 patients, including 705 with breast cancer (BC), 23 with ovarian cancer (OC), 10 with both, and 254 relatives of high-risk patients who underwent BRCA testing at the National Cancer Center of Korea from January 2008 to December 2016.We analyzed patterns of and factors in RR management. RESULTS: Of the 992 patients, 220 (22.2%) were carriers of BRCA pathogenic variants. About 92.3% (203/220) had a family history of BC and/or OC,which significantly differed between BRCA1 and BRCA2 carriers (p < 0.001). All 41 male carriers chose surveillance. Of the 179 female carriers, 59 of the 83 carriers (71.1%) with BC and the 39 of 79 unaffected carriers (49.4%) underwent RR management. None of the carriers affected with OC underwent RR management. Of the management types, RRSO had the highest rate (42.5%) of patient choice. The rate of RR surgery was significantly higher after 2013 than before 2013 (46.3% [74/160] vs. 31.6% [6/19], p < 0.001). CONCLUSION: RRSO was the preferred management for carriers of BRCA pathogenic variants. The most important factors in treatment choice were NHIS reimbursement and/or the severity of illness.
Breast
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Breast Neoplasms
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Female
;
Humans
;
Korea
;
Male
;
National Health Programs
;
Ovarian Neoplasms
;
Prophylactic Surgical Procedures

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