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Breast cancer
Implication and Influence of Multigene Panel Testing with Genetic Counseling in Korean Patients with BRCA1/2 Mutation-Negative Breast Cancer
Ji Soo Park, Saeam Shin, Yoon Jung Lee, Seung-Tae Lee, Eun Ji Nam, Jung Woo Han, Sun Hwa Lee, Tae Il Kim, Hyung Seok Park
Cancer Res Treat. 2022;54(4):1099-1110.   Published online November 17, 2021
DOI: https://doi.org/10.4143/crt.2021.978
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The aim of the study was to evaluate the clinical implication of multigene panel testing of beyond BRCA genes in Korean patients with BRCA1/2 mutation-negative breast cancer.
Materials and Methods
Between 2016 and 2019, a total of 700 BRCA1/2 mutation-negative breast cancer patients received comprehensive multigene panel testing and genetic counseling. Among them, 347 patients completed a questionnaire about cancer worry, genetic knowledge, and preference for the method of genetic tests during pre- and post-genetic test counseling. The frequency of pathogenic and likely pathogenic variants (PV/LPV) were analyzed.
Results
At least one PV/LPV of 26 genes was found in 76 out of 700 patients (10.9 %). The rate for PV/LPV was 3.4% for high-risk genes (17 PALB2, 6 TP53, and 1 PTEN). PV/LPVs of clinical actionable genes for breast cancer management, high-risk genes and other moderate-risk genes such as ATM, BARD1, BRIP, CHEK2, NF1, and RAD51D, were observed in 7.4%. Patients who completed the questionnaire showed decreased concerns about the risk of additional cancer development (average score, 4.21 to 3.94; p < 0.001), influence on mood (3.27 to 3.13; p < 0.001), influence on daily functioning (3.03 to 2.94; p=0.006); and increased knowledge about hereditary cancer syndrome (66.9 to 68.8; p=0.025) in post-test genetic counseling. High cancer worry scales (CWSs) were associated with age ≤ 40 years and the identification of PV/LPV. Low CWSs were related to the satisfaction of the counselee.
Conclusion
Comprehensive multigene panel test with genetic counseling is clinically applicable. It should be based on interpretable genetic information, consideration of potential psychological consequences, and proper preventive strategies.

Citations

Citations to this article as recorded by  
  • Evidence-based advancements in breast cancer genetic counseling: a review
    Zahra Batool, Mohammad Amjad Kamal, Bairong Shen
    Breast Cancer.2025; 32(2): 258.     CrossRef
  • Exploring Literacy and Knowledge Gaps and Disparities in Genetics and Oncogenomics Among Cancer Patients and the General Population: A Scoping Review
    Katerina Nikitara, Maria Luis Cardoso, Astrid Moura Vicente, Célia Maria Batalha Silva Rasga, Roberta De Angelis, Zeina Chamoun Morel, Arcangela De Nicolo, Maria Nomikou, Christina Karamanidou, Christine Kakalou
    Healthcare.2025; 13(2): 121.     CrossRef
  • Korean patients with hereditary cancer: a prospective multicentre cohort study protocol exploring psychosocial and health outcomes
    Jun-Kyu Kim, Mi-Ae Jang, Jong Eun Park, Dongju Won, Jung-Sook Ha, Kyoung-Bo Kim, Boyoung Park, Sun-Young Kong
    BMJ Open.2025; 15(2): e093905.     CrossRef
  • PALB2 germline pathogenic variants: frequency, clinical features, and functional analysis of c.3350+5G>A variant in 3987 Korean cancer patients
    M.-C. Kang, S. Lee, H. Kim, H.-S. Kang, S.-Y. Jung, J.-A. Hwang, J. Kwon, K.S. Lee, M.C. Lim, S.-Y. Park, S.H. Sim, W. Choi, J.E. Park, E.-H. Cho, S.-Y. Kong
    ESMO Open.2025; 10(3): 104132.     CrossRef
  • Human epidermal growth factor receptor-2 expression and subsequent dynamic changes in patients with ovarian cancer
    Yoo-Na Kim, Yun Soo Chung, Eunhyang Park, Seung Tae Lee, Jung-Yun Lee
    Scientific Reports.2024;[Epub]     CrossRef
  • 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 Research and Treatment.2024; 56(3): 802.     CrossRef
  • Germline RAD51C and RAD51D Mutations in High-Risk Chinese Breast and/or Ovarian Cancer Patients and Families
    Ava Kwong, Cecilia Yuen Sze Ho, Chun Hang Au, Sze Keong Tey, Edmond Shiu Kwan Ma
    Journal of Personalized Medicine.2024; 14(8): 866.     CrossRef
  • Prevalence Estimation of the PALB2 Germline Variant in East Asians and Koreans through Population Database Analysis
    Jong Eun Park, Min-Chae Kang, Taeheon Lee, Eun Hye Cho, Mi-Ae Jang, Dongju Won, Boyoung Park, Chang-Seok Ki, Sun-Young Kong
    Cancers.2024; 16(19): 3318.     CrossRef
  • Clinical Significance of PALB2 Pathogenic Germline Variant
    Min-Chae Kang, R.N., Jong Eun Park, Mi-Ae Jang, Dongju Won, Boyoung Park, Seeyoun Lee, Dong Ock Lee, Kum Hei Ryu, Yoon-Jung Chang, Sun-Young Kong
    Laboratory Medicine Online.2024; 14(4): 311.     CrossRef
  • Clinicopathological Features and Oncological Outcomes of Germline Partner and Localizer of Breast Cancer 2-Mutated Breast Cancer in Korea
    Chayanee Sae-lim, Seongyeon Jo, Shinyoung Park, Taeyong Kweon, Jeea Lee, Yoonjung Lee, Sun Hwa Lee, Dongju Won, Eun Ji Nam, Jung Woo Han, Tae Il Kim, Ji Soo Park, Hyung Seok Park
    Journal of Breast Cancer.2024; 27(6): 372.     CrossRef
  • Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer
    Antonella Turchiano, Marilidia Piglionica, Stefania Martino, Rosanna Bagnulo, Antonella Garganese, Annunziata De Luisi, Stefania Chirulli, Matteo Iacoviello, Michele Stasi, Ornella Tabaku, Eleonora Meneleo, Martina Capurso, Silvia Crocetta, Simone Lattaru
    Genes.2023; 14(8): 1530.     CrossRef
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Clinicopathological Features of Patients with the BRCA1 c.5339T>C (p.Leu1780Pro) Variant
Hyung Seok Park, Jai Min Ryu, Ji Soo Park, Seock-Ah Im, So-Youn Jung, Eun-Kyu Kim, Woo-Chan Park, Jun Won Min, Jeeyeon Lee, Ji Young You, Jeong Eon Lee, Sung-Won Kim
Cancer Res Treat. 2020;52(3):680-688.   Published online January 28, 2020
DOI: https://doi.org/10.4143/crt.2019.351
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Recent studies revealed the BRCA1 c.5339T>C, p.Leu1780Pro variant (L1780P) is highly suggested as a likely pathogenic. The aim of this study was to evaluate clinicopathologic features of L1780P with breast cancer (BC) using multicenter data from Korea to reinforce the evidence as a pathogenic mutation and to compare L1780P and other BRCA1/2mutations using Korean Hereditary Breast Cancer (KOHBRA) study data.
Materials and Methods
The data of 54 BC patients with L1780P variant from 10 institutions were collected and the clinicopathologic characteristics of the patients were reviewed. The hereditary breast and/or ovarian cancer–related characteristics of the L1780P variant were compared to those of BC patients in the KOHBRA study.
Results
The median age of all patients was 38 years, and 75.9% of cases showed triple-negative breast cancer. Comparison of cases with L1780P to carriers from the KOHBRA study revealed that the L1780P patients group was more likely to have family history (FHx) of ovarian cancer (OC) (24.1% vs. 19.6% vs. 11.2%, p < 0.001 and p=0.001) and a personal history of OC (16.7% vs. 2.9% vs. 1.3%, p=0.003 and p=0.001) without significant difference in FHx of BC and bilateral BC. The cumulative risk of contralateral BC at 10 years after diagnosis was 31.9%, while the cumulative risk of OC at 50 years of age was 20.0%. Patients with L1780P showed similar features with BRCA1 carriers and showed higher penetrance of OC than patients with other BRCA1 mutations.
Conclusion
L1780P should be considered as a pathogenic mutation. Risk-reducing salpingo-oophorectomy is highly recommended for women with L1780P.

Citations

Citations to this article as recorded by  
  • Whole Exome-Wide Association Identifies Rare Variants in GALNT9 Associated with Middle Eastern Papillary Thyroid Carcinoma Risk
    Rong Bu, Abdul K. Siraj, Saud Azam, Kaleem Iqbal, Zeeshan Qadri, Maha Al-Rasheed, Saif S. Al-Sobhi, Fouad Al-Dayel, Khawla S. Al-Kuraya
    Cancers.2023; 15(17): 4235.     CrossRef
  • Feasibility of targeted cascade genetic testing in the family members of BRCA1/2 gene pathogenic variant/likely pathogenic variant carriers
    Jeeyeon Lee, Ji Yeon Ham, Ho Yong Park, Jin Hyang Jung, Wan Wook Kim, Byeongju Kang, Yee Soo Chae, Soo Jung Lee, In Hee Lee, Nan Young Lee
    Scientific Reports.2022;[Epub]     CrossRef
  • Molecular Characterization of BRCA1 c.5339T>C Missense Mutation in DNA Damage Response of Triple-Negative Breast Cancer
    Jeong Dong Lee, Won-Ji Ryu, Hyun Ju Han, Tae Yeong Kim, Min Hwan Kim, Joohyuk Sohn
    Cancers.2022; 14(10): 2405.     CrossRef
  • Discovery of BRCA1/BRCA2 founder variants by haplotype analysis
    Won Kyung Kwon, Hyeok-Jae Jang, Jeong Eon Lee, Yeon Hee Park, Jai Min Ryu, Jonghan Yu, Ja-Hyun Jang, Jong-Won Kim
    Cancer Genetics.2022; 266-267: 19.     CrossRef
  • Local Laboratory Testing of Germline BRCA Mutations vs. Myriad: A Single-Institution Experience in Korea
    Joohyun Hong, Jiyun Lee, Minsuk Kwon, Ji-Yeon Kim, Jong-Won Kim, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
    Diagnostics.2021; 11(2): 370.     CrossRef
  • Analysis of BRCA1/2 variants of unknown significance in the prospective Korean Hereditary Breast Cancer study
    Joo Heung Kim, Sunggyun Park, Hyung Seok Park, Ji Soo Park, Seung-Tae Lee, Sung-Won Kim, Jong Won Lee, Min Hyuk Lee, Sue K. Park, Woo-Chul Noh, Doo Ho Choi, Wonshik Han, Sung Hoo Jung
    Scientific Reports.2021;[Epub]     CrossRef
  • A Population-Based Analysis of BRCA1/2 Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study
    Kyung-Sun Park, Woochang Lee, Moon-Woo Seong, Sun-Young Kong, Kyung-A Lee, Jung-Sook Ha, Eun-Hae Cho, Sung-Hee Han, Inho Park, Jong-Won Kim
    Cancers.2021; 13(9): 2192.     CrossRef
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  • 189 Download
  • 7 Web of Science
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Detection of Germline Mutations in Patients with Epithelial Ovarian Cancer Using Multi-gene Panels: Beyond BRCA1/2
Kyung Jin Eoh, Ji Eun Kim, Hyung Seok Park, Seung-Tae Lee, Ji Soo Park, Jung Woo Han, Jung-Yun Lee, Sunghoon Kim, Sang Wun Kim, Jae Hoon Kim, Young Tae Kim, Eun Ji Nam
Cancer Res Treat. 2018;50(3):917-925.   Published online September 27, 2017
DOI: https://doi.org/10.4143/crt.2017.220
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Next-generation sequencing (NGS) allows simultaneous sequencing of multiple cancer susceptibility genes and may represent a more efficient and less expensive approach than sequential testing. We assessed the frequency of germline mutations in individuals with epithelial ovarian cancer (EOC), using multi-gene panels and NGS.
Materials and Methods
Patients with EOC (n=117) with/without a family history of breast or ovarian cancer were recruited consecutively, from March 2016 toDecember 2016.GermlineDNAwas sequenced using 35-gene NGS panel, in order to identify mutations. Upon the detection of a genetic alteration using the panel, results were cross-validated using direct sequencing.
Results
Thirty-eight patients (32.5%) had 39 pathogenic or likely pathogenic mutations in eight genes, including BRCA1 (n=21), BRCA2 (n=10), BRIP1 (n=1), CHEK2 (n=2), MSH2 (n=1), POLE (n=1), RAD51C (n=2), and RAD51D (n=2). Among 64 patients with a family history of cancer, 27 (42.2%) had 27 pathogenic or likely pathogenic mutations, and six (9.3%) had mutations in genes other than BRCA1/2, such as CHECK2, MSH2, POLE, and RAD51C. Fifty-five patients (47.0%) were identified to carry only variants of uncertain significance.
Conclusion
Using the multi-gene panel test, we found that, of all patients included in our study, 32.5% had germline cancer-predisposing mutations. NGS was confirmed to substantially improve the detection rates of a wide spectrum of mutations in EOC patients compared with those obtained with the BRCA1/2 testing alone.

Citations

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    Journal of Personalized Medicine.2024; 14(8): 866.     CrossRef
  • Clinical Significance of PALB2 Pathogenic Germline Variant
    Min-Chae Kang, R.N., Jong Eun Park, Mi-Ae Jang, Dongju Won, Boyoung Park, Seeyoun Lee, Dong Ock Lee, Kum Hei Ryu, Yoon-Jung Chang, Sun-Young Kong
    Laboratory Medicine Online.2024; 14(4): 311.     CrossRef
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Prognostic Factors and Scoring Model for Survival in Metastatic Biliary Tract Cancer
Hyung Soon Park, Ji Soo Park, You Jin Chun, Yun Ho Roh, Jieun Moon, Hong Jae Chon, Hye Jin Choi, Joon Seong Park, Dong Ki Lee, Se-Joon Lee, Dong Sup Yoon, Hei-Cheul Jeung
Cancer Res Treat. 2017;49(4):1127-1139.   Published online February 6, 2017
DOI: https://doi.org/10.4143/crt.2016.538
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Metastatic biliary tract cancer (mBTC) has a dismal prognosis. In this study, an independent dataset of patients with mBTC was used to implement and validate a routine clinico-laboratory parameter-based scoring model for risk group identification.
Materials and Methods
From September 2006 to February 2015, 482 patients with mBTC were assigned randomly (ratio, 7:3) into investigational (n=340) and validation datasets (n=142). The continuous variables were dichotomized using a normal range or the best cutoff values determined using the Contal and O'Quigley statistical methods. Following a Cox’s proportional hazard model, the scoring model was derived by summing the rounded chi-square scores for the factors identified by multivariate analysis.
Results
The performance status (Eastern Cooperative Oncology Group 3-4), hypoalbuminemia (< 3.4 mg/dL), carcinoembryonic antigen (≥ 9 ng/mL), neutrophil-to-lymphocyte ratio (≥ 3.0), and carbohydrate antigen 19-9 (≥ 120 U/mL) were identified as independent prognosticators (Harrell’s C index, 0.682; integrated area under the curve, 0.653). Survival was clearly correlated with the risk groups (low, intermediate, and high, 14.0, 7.3, and 2.3 months, respectively; p < 0.001). The prognosis was also discriminative in the validation data set (median survival, 16.7, 7.5, and 1.9 months, respectively; p < 0.001). Chemotherapy did not offer any survival benefits for high-risk patients.
Conclusion
These proposed prognostic criteria for mBTC can facilitate accurate patient risk stratification and treatment-related decision-making.

Citations

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Identification of a Novel BRCA1 Pathogenic Mutation in Korean Patients Following Reclassification of BRCA1 and BRCA2 Variants According to the ACMG Standards and Guidelines Using Relevant Ethnic Controls
Ji Soo Park, Eun Ji Nam, Hyung Seok Park, Jung Woo Han, Jung-Yun Lee, Jieun Kim, Tae Il Kim, Seung-Tae Lee
Cancer Res Treat. 2017;49(4):1012-1021.   Published online January 17, 2017
DOI: https://doi.org/10.4143/crt.2016.433
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Comparison of variant frequencies in the general population has become an essential part of the American College of Medical Genetics and Genomics (ACMG) standards and guidelines for interpreting sequence variants. We determined the optimal number of relevant ethnic controls that should be used to accurately calculate the odds ratio (OR) of genetic variants.
Materials and Methods
Using the ACMG guidelines, we reclassified BRCA1 and BRCA2 mutations and variants of unknown significance in 745 Korean patients susceptible to hereditary breast and ovarian cancer compared with 1,314 Korean population controls.
Results
We observed that the ORs were falsely inflated when we analyzed several variants using non-Korean population data. Our simulation indicated that the number of controls needed for the lower limit of a 95% confidence interval to exceed 1.0 varied according to the frequency of the variant in each patient group, with more than 820 controls needed for a variant existing in 1% of cases. Using a sufficient number of relevant population data, we could efficiently classify variants and identified the BRCA1 p.Leu1780Pro mutation as a possible pathogenic founder mutation in Korean patients.
Conclusion
Our study suggests that BRCA1 p.Leu1780Pro is a novel pathogenic mutation found in Korean patients. We also determined the optimal number of relevant ethnic controls needed for accurate variant classification according to the ACMG guidelines.

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Comparison of Clinical Outcomes of BRCA1/2 Pathologic Mutation, Variants of Unknown Significance, or Wild Type Epithelial Ovarian Cancer Patients
Kyung Jin Eoh, Hyung Seok Park, Ji Soo Park, Seung-Tae Lee, Jeongwoo Han, Jung-Yun Lee, Sang Wun Kim, Sunghoon Kim, Young Tae Kim, Eun Ji Nam
Cancer Res Treat. 2017;49(2):408-415.   Published online July 27, 2016
DOI: https://doi.org/10.4143/crt.2016.135
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to investigate the clinical features of epithelial ovarian cancer (EOC) patients according to BRCA1/2 mutation status (mutation, variant of uncertain significance [VUS], or wild type).
Materials and Methods
We analyzed 116 patients whose BRCA1/2 genetic test results were available for mutation type and clinical features, including progression-free survival (PFS), overall survival (OS), and response rate. These characteristics were compared according to BRCA1/2 mutation status.
Results
Thirty-seven (37/116, 31.9%) BRCA1/2 mutations were identified (BRCA1, 30; BRCA2, 7). Mutation of c.3627_3628insA (p.Leu1209_Glu1210?fs) in BRCA1 was observed in five patients (5/37, 13.5%). Twenty-five patients had BRCA1/2 VUSs (25/116, 21.6%). Personal histories of breast cancer were observed in 48.6% of patients with BRCA1/2 mutation (18/37), 16.0% of patients with BRCA1/2 VUS (4/25), and 7.4% of patients with BRCA wild type (4/54) (p < 0.001). Patients with BRCA1/2 mutation showed longer OS than those with BRCA1/2 wild type (p=0.005). No significant differences were detected in PFS, OS, or response rates between patients with BRCA1/2 VUS and BRCA1/2 mutation (p=0.772, p=0.459, and p=0.898, respectively).
Conclusion
Patientswith BRCA1/2 mutation had longer OS than thosewith BRCA1/2wild type. Patients with BRCA1/2 mutation and BRCA1/2 VUS displayed similar prognoses.

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Prognostic Scoring Index for Patients with Metastatic Pancreatic Adenocarcinoma
Hyung Soon Park, Hye Sun Lee, Ji Soo Park, Joon Seong Park, Dong Ki Lee, Se-Joon Lee, Dong Sup Yoon, Min Goo Lee, Hei-Cheul Jeung
Cancer Res Treat. 2016;48(4):1253-1263.   Published online February 3, 2016
DOI: https://doi.org/10.4143/crt.2015.400
AbstractAbstract PDFPubReaderePub
Purpose
This study focused on implementation of a prognostic scoring index based on clinico-laboratory parameters measured routinely on admission in metastatic pancreatic cancer patients.
Materials and Methods
Records from 403 patients of metastatic disease were analyzed retrospectively. Continuous variables were dichotomized according to the normal range or the best cut-off values statistically determined by Contal and O’Quigley method, and then analyzed in association with prognosis—overall survival (OS), using Cox’s proportional hazard model. Scores were calculated by summing the rounded chi-square scores for the factors that emerged in the multivariate analysis.
Results
Performance status, hemoglobin, leucocyte count, neutrophil-lymphocyte ratio, and carcinoembryonic antigen were independent factors for OS. When patients were divided into three risk groups according to these factors, median survival was 11.7, 6.2, and 1.3 months for the low, intermediate, and high-risk groups, respectively (p < 0.001). Palliative chemotherapy has a significant survival benefit for low and intermediate-risk patients (median OS; 12.5 months vs. 5.9 months, p < 0.001 and 8.0 months vs. 2.0 months, p < 0.001, respectively).
Conclusion
We advocate the use of a multivariable approach with continuous variables for prognostic modeling. Our index is helpful in accurate patient risk stratification and may aid in treatment selection.

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Prognostic Factors of Second and Third Line Chemotherapy Using 5-FU with Platinum, Irinotecan, and Taxane for Advanced Gastric Cancer
Ji Soo Park, Jae Yun Lim, Seung Kyo Park, Min Kyung Kim, Hee Sung Ko, Sun Och Yoon, Jong Won Kim, Seung Ho Choi, Jae Yong Cho
Cancer Res Treat. 2011;43(4):236-243.   Published online December 27, 2011
DOI: https://doi.org/10.4143/crt.2011.43.4.236
AbstractAbstract PDFPubReaderePub
PURPOSE
The aims of this study are to find out whether the sequence of chemotherapeutic regimens including second- and third-line taxane and irinotecan influences the survival of patients with unresectable gastric carcinoma and to identify clinical characteristics of patients with improved response.
MATERIALS AND METHODS
Fifty gastric carcinoma patients who were treated by third-line sequential chemotherapy between November 2004 and July 2010 were enrolled in this study. Their overall survival (OS) and time to progression (TTP) were set up as primary and secondary end points. For the sequence of chemotherapy regimen, two arms were used. Arm A was defined as 5-fluorouracil (5-FU)+cisplatin (FP) or folinic acid, 5-FU and oxaliplati (FOLFOX), followed by folinic acid, 5-FU and irinotecan (FOLFIRI), and paclitaxel or docetaxel plus 5-FU, with or without epirubicin. Arm B was defined as FP or FOLFOX, followed by paclitaxel or docetaxel plus 5-FU, and FOLFIRI.
RESULTS
The median OS of all patients was 16.0 months (95% confidence interval, 13.6 to 18.3 months), which is longer than historical control of patients who did not receive third-line chemotherapy. The sequence of second and third-line regimen, including irinotecan and taxane, did not present significant difference in OS or TTP after failure of 5-FU with platinum chemotherapy. In survival analysis of patients' clinicopathologic characteristics, poor prognosis was shown in patients with poorly differentiated histologic features, elevated serum carcinoembryonic level, and shorter TTP of first line chemotherapy.
CONCLUSION
It is possible for patients to respond differently to chemotherapy due to differences in clinical features and underlying gene expression profiles. Development of individualized chemotherapy regimens based on gene expression profiles is warranted.

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