GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • American Association for Cancer Research (AACR)  (9)
Material
Publisher
  • American Association for Cancer Research (AACR)  (9)
Person/Organisation
Language
Years
Subjects(RVK)
  • 1
    Online Resource
    Online Resource
    Abstract P5-03-14: Prevalence of germline BRCA mutations in unselected Korean patients with HER2-negative breast cancer: A Prospective cohort study
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 5_Supplement ( 2023-03-01), p. P5-03-14-P5-03-14
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 5_Supplement ( 2023-03-01), p. P5-03-14-P5-03-14
    Abstract: Backgrounds Since OlympiAD study, National Comprehensive Cancer Network guideline recommends assessment of germline BRCA1/2 mutation in all patients with recurrent or metastatic breast cancer to identify candidates for PARP inhibitor therapy, which is not always possible in clinical practice due to limited resources for testing. Data on the prevalence of gBRCA mutation is still lacking, especially in patients with non-high risk for hereditary breast and ovarian cancer syndrome. In this study, we investigated prevalence of gBRCA mutation in unselected Korean patients with HER2-negative advanced BC in a prospective cohort and analyzed oncologic outcome. Methods Eligible patients were diagnosed with HER2-negative advanced BC and had initiated palliative systemic treatment. Peripheral blood was prospectively drawn from each patient and gBRCA mutation status was assessed by next generation sequencing using NGeneBio BRCAaccuTest®. In 100 patients, somatic mutations including BRCA1/2 from tumor tissue were investigated using targeted panel sequencing. To estimate the prevalence of gBRCA mutation with margin of error to be no more than ±4% at the 95% confidence interval in a population size of 20,000, 583 patients were to be enrolled. Results A total of 583 patients were enrolled between Oct 2019 and Mar 2022, and the prevalence of gBRCA mutation was analyzed in 570 patients, excluding ineligible patients. Median age was 54 years old (range 26-87) and 567 patients were female. 475 patients had HR+/HER2- BC and 94 patients had triple negative breast cancer (TNBC). The overall prevalence of gBRCA1/2 pathogenic mutation was 7.3% (42/570) in unselected patients. The prevalence of gBRCA1 mutation was 1.6%(9/570) overall, 0.8%(4/475) in HR+/HER2- BC, and 5.3%(5/94) in TNBC. The prevalence of gBRCA2 mutation was 5.8%(33/570) overall, 6.3%(30/475) in HR+/HER2- BC, 3.2%(3/94) in TNBC. Prevalence in low risk TNBC ( & gt;60 years at first BC diagnosis, no known family history of relevant cancer and unilateral breast cancer) was 10.5% (2/19, all 2 patients had gBRCA2 mutation). Prevalence in low risk HR+/HER2- ( & gt;40 years at first BC diagnosis, no known family history of relevant cancer and unilateral breast cancer) was 5.9% (18/307, 17 patients had gBRCA2 mutation). The overall prevalence of gBRCA1/2 pathogenic mutation in Korean patients with low risk HER2-negative advanced BC was 6.1%. The result of somatic mutation, treatment patterns and clinical outcome according to gBRCA1/2 mutation will be further analyzed. Conclusions The prevalence of gBRCA mutation among Korean patients with HER2-negative advanced BC classified as low risk (6.1%) in this study supports routine testing of gBRCA mutation in this population. Citation Format: Hee Kyung Ahn, Jee Hung Kim, Mirae Kim, Seri Park, Su-Jin Koh, Joo Hyuk Sohn, Myoung Joo Kang, Kyung Hae Jung, Kyoung Eun Lee, Jieun Lee, Sung Ae Koh, Yee Soo Chae, Jae Ho Byun, In Hae Park, Hee-Jun Kim, Jee Hyun Kim, Han Jo Kim, Joo Young Jung, Jung Lim Lee, Yoon Young Cho, Kyong Hwa Park, Ji-Yeon Kim, Seock-Ah Im, Yeon Hee Park. Prevalence of germline BRCA mutations in unselected Korean patients with HER2-negative breast cancer: A Prospective cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-14.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS22-P5-03-14
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Abstract C10: Class III β -tubulin predicts pathological response to neoadjuvant docetaxel-based chemotherapy in breast cancer patients.
    American Association for Cancer Research (AACR) ; 2011
    In:  Molecular Cancer Therapeutics Vol. 10, No. 11_Supplement ( 2011-11-12), p. C10-C10
    Details
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 10, No. 11_Supplement ( 2011-11-12), p. C10-C10
    Abstract: Background: Class III β-tubulin has been suggested as a potential predictor of taxane response for several cancers including breast cancer, although controversies exist. We evaluated correlations between class III β-tubulin and docetaxel response in neoadjuvant setting of breast cancer, focusing on pathological response which is considered the most powerful predictor of outcome. Materials and Methods: Fifty-five patients with primary breast cancer who had undergone neoadjuvant doxetaxel and adriamycin were included in this study. Class III β-tubulin was measured by immunohistochemistry in prechemotherapy paraffin-embedded tumor tissues. The cutoff value of ‘high’ and ‘low’ expression of class III β-tubulin was set at 50% of tumor cell staining. ‘Good pathological response’ was defined by pathological complete response (pCR) or microscopic residual disease (i.e., breast tumor ≤1cm and negative axillary node). The counterpart was designated as ‘poor pathological response’. Results: Before chemotherapy, 14 patients were in clinical stage II and 41 were in clinical stage III. After the median 4 cycles of preoperative chemotherapy, clinical downstaging was observed in 40 patients whereas clinical staging did not change in the remaining patients. Eleven patients (20%) showed good pathological response (pCR, 6; microscopic residual disease, 5) and 44 (80%) showed poor pathological response. Thirty-six (65.5%) and 19 patients (34.5%) were categorized into low and high class III β-tubulin groups, respectively. Low class III β-tubulin was associated with low histologic grade (P=0.052). However, in multivariate logistic regression adjusted by known prognostic factors including histologic grade, low expression of class III β-tubulin (hazard ratio = 11.1; P = 0.049) and triple negative status (hazard ratio = 6.86; P = 0.022) were independent predictors of good pathological response. At the median follow-up of 40.8 months after surgery, recurrence occurred in 11 patients (5 in low class III β-tubulin group; 6 in high). Low expression of class III β-tubulin showed a favorable risk of relapse (P=0.152) which did not reach statistical significance probably due to short follow-up period. Conclusions: Low expression of class III β-tubulin by immunohistochemistry predicts good pathological response to neoadjuvant docetaxel in breast cancer, suggesting implications for improving chance to define docetaxel-beneficial group in this setting. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C10.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    URL: Article
    DOI: 10.1158/1535-7163.TARG-11-C10
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2062135-8
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Phase II Clinical and Exploratory Biomarker Study of Dacomitinib in Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of Head and Neck
    American Association for Cancer Research (AACR) ; 2015
    In:  Clinical Cancer Research Vol. 21, No. 3 ( 2015-02-01), p. 544-552
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 21, No. 3 ( 2015-02-01), p. 544-552
    Abstract: Purpose: The goals of this study were to investigate the clinical activity, safety, and biomarkers of dacomitinib, an irreversible tyrosine kinase inhibitor of EGFR, HER2, and HER4, in recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). Experimental Design: Patients were eligible if the diseases were not amenable to curative treatment and had progressed on platinum-based chemotherapy, and were treated with dacomitinib 45 mg/day. The primary endpoint was objective response rate by RECISTv1.1. Exploratory analysis included the characterization of somatic mutation, gene copy number, gene expression, p16INK4A expression by IHC, and investigation of their relationship with clinical outcomes. Results: Forty-eight patients were evaluable for efficacy and toxicity. Ten patients (20.8%) had partial responses and 31 patients (65%) had stable diseases. The median progression-free survival (PFS) and overall survival (OS) were 3.9 months [95% confidence interval (CI), 2.9–5.0] and 6.6 months (95% CI, 5.4–10.3). Adverse events were mostly grade 1–2. Mutations in the PI3K pathway (PIK3CA, PTEN) and high expression of inflammatory cytokines (IL6, IL8, IL1A, IL1B, IL4, and TNF) were significantly associated with shorter PFS (2.9 vs. 4.9 months without mutations, P = 0.013; 2.8 vs. 9.9 months with low expression, P = 0.004). Those harboring PI3K pathway mutations or high inflammatory cytokine expression had shorter median OS (6.1 vs. 12.5 months lacking PI3K pathway mutations and with low inflammatory cytokine expression, P = 0.005). Conclusions: Dacomitinib demonstrated clinical efficacy with manageable toxicity in platinum-failed R/M-SCCHN patients. Screening of PI3K pathway mutation and inflammatory cytokine expression may help identify which R/M-SCCHN patients are likely to gain benefit from dacomitinib. Clin Cancer Res; 21(3); 544–52. ©2014 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-14-1756
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Abstract 6371: Deep learning algorithm for multi-cancer detection and classification using cf-WGS
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 12_Supplement ( 2022-06-15), p. 6371-6371
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 12_Supplement ( 2022-06-15), p. 6371-6371
    Abstract: Purpose: Several cell-free DNA (cf-DNA) features, such as genome-wide coverage, fragment size, and fragment end motif frequency, have shown their potentials for cancer detection. In this study, we developed two independent models, GC (gross chromatin), and FEMS (fragment end motif frequency and size). Each model uses images generated from genome-wide normalized sequencing coverage and cf-DNA fragment end motif frequencies according to the different cf-DNA size profiles. Then we integrated them into a single ensemble model to improve cancer detection and multi-cancer type classification accuracy. Methods: Low depth cf-WGS data was generated from 1,396 patients (stage I: 14.9%, stage II: 35.6%, stage III: 24.9%, stage IV: 24.2%, unknown: 0.4%) with breast (n=702), liver (n=213), esophageal (n=155), ovarian (n=151), pancreatic (n=85), lung (n=53), head and neck (n=16), biliary tract (n=15), and colon cancer (n=6) and 417 healthy individuals. Samples were randomly split into training, validation, and test set stratifying cancer type and stages. Cancer types with a small number of samples ( & lt;20) were excluded for multi-cancer type classification. Each model was trained using a convolutional neural network, then integrated into a single ensemble model by averaging the predicted probabilities calculated from each model. Results: For cancer detection, the ensemble model achieved sensitivities of 85.2% [95% confidence interval (CI): 71.8% to 94.5%], 74.9% (CI: 68.0% to 88.0%), 73.2% (CI: 66.7% to 85.9%) at a specificity of 95%, 98% and 99% and the AUC value of 0.97(CI: 0.95-0.99) in the test dataset. By the cancer stages, sensitivity was 62.8% (CI: 48.8% to 83.7%) in stage I, 66.3% (CI: 57.7% to 82.7%) in stage II, 85.9% (CI: 77.5% to 94.4%) in stage III, and 76.1% (CI: 63.4% to 87.3%) in stage IV at 99% specificity. For multi-cancer classification, the overall accuracy of 85.1% (CI: 80.4% to 89.3%) was achieved including 6 cancer types. Conclusions: Highly sensitive and accurate deep learning model for cancer detection and multi-cancer classification was generated by combining different types of cf-DNA features. This result provides the opportunity for general population multi-cancer screening using various cf-DNA features. Citation Format: Tae-Rim Lee, Jin Mo Ahn, Joo Hyuk Sohn, Sook Ryun Park, Min Hwan Kim, Gun Min Kim, Ki-Byung Song, Eunsung Jun, Dongryul Oh, Jeong-Won Lee, Joseph J Noh, Young Sik Park, Sun-Young Kong, Sang Myung Woo, Bo Hyun Kim, Eui Kyu Chie, Hyun-Cheol Kang, Youn Jin Choi, Ki-Won Song, Jeong-Sik Byeon, Junnam Lee, Dasom Kim, Chang-Seok Ki, Eunhae Cho. Deep learning algorithm for multi-cancer detection and classification using cf-WGS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6371.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2022-6371
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Abstract P6-08-33: Prognostic value of axillary nodal ratio after neoadjuvant chemotherapy of AC followed by docetaxel: A multicenter retrospective cohort study
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 9_Supplement ( 2015-05-01), p. P6-08-33-P6-08-33
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 9_Supplement ( 2015-05-01), p. P6-08-33-P6-08-33
    Abstract: Background: The ratio of involved to retrieved lymph nodes (LNR) is suggested as a prognostic factor in operable breast cancer. However, there are conflicting results regarding its clinical significance after neoadjuvant chemotherapy. We investigated the prognostic value of LNR with a thorough evaluation of potential prognostic factors in a large cohort constructed from Health Insurance Review and Assessment Service database of Korea. Patients and method: This retrospective analysis is based on the data of 814 patients with clinical stage II/III breast cancer treated with four cycles of adriamycin/cyclophosphamide (AC) followed by four cycles of docetaxel (DOC) before surgery. We evaluated the clinical significance of the LNR (3 categories: Low, 0-0.20 vs. Intermediate, 0.21-0.65 vs. High, 0.66 -1.00) using Kaplan-Meier method, log-rank test, and Cox proportional hazard regression model. Result: A total of 799 patients underwent breast surgery (Median age 45, range 16-74; Mastectomy 369, Lumpectomy 380, and Others 50). Axillary lymph node dissection was performed in 704 (88.1%) patients. Pathologic complete response (pCR, pT0/isN0) was achieved in 129 (16.1%) of 799 patients (HR+/HER2-, 34/373 [9.1%]; HER2+, 45/210 [21.4%] ; TNBC 50/216 [23.1%]). The mean numbers of involved LN and retrieved LN were 2.70 (range 0-42) and 13.98 (range 1-64), respectively. The mean LNR was 0.17 (Low, 574 [71.8%] ; Intermediate, 170 [21.3%]; High, 55 [6.9%] ). In univariate analysis, LNR was significantly associated with worse relapse-free survival (3-yr RFS rate 84.8% in low vs. 66.2% in intermediate vs. 54.3% in high; P & lt;0.0001, log-rank test). In multivariate analysis, LNR was not significantly associated with recurrence after adjustment of other clinical factors (Age, histologic grade, intrinsic subtype, ypT-stage, ypN-stage, lymphatic or vascular invasion, and pCR). Multivariate analysis for relapse-free survival P-valueHR95%CIAGE ( & lt;50, ≥50)0.157--ypT-stage & lt;0.0001--ypN-stage0.035--pCR (T0/isN0)0.027--Lymphovascular invasion0.040--Subtype & lt;0.0001--Histologic grade0.001--LNR Low (0-0.20)0.9541.00-LNR Intermediate (0.21-0.65)0.9731.010.55-1.86LNR High (0.66-1.00)0.7971.120.48-2.59 Conclusion: LNR is not superior to ypN-stage in predicting clinical outcome of breast cancer after neoadjuvant chemotherapy. Citation Format: Se Hyun Kim, Jee Hyun Kim, Tae-Yong Kim, In Sil Choi, Yee Soo Chae, Sun Kyung Baek, Seok Yun Kang, In Hae Park, Yoon Ji Choi, Soohyeon Lee, Joo Hyuk Sohn, Yeon-Hee Park, Young-Hyuck Im, Jin-Hee Ahn, Sung-Bae Kim, Kyung Hae Jung. Prognostic value of axillary nodal ratio after neoadjuvant chemotherapy of AC followed by docetaxel: A multicenter retrospective cohort study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-33.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS14-P6-08-33
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Abstract 2053: Molecular characterization of BRCA1 c.5339T〉C missense mutation in DNA damage response of triple-negative breast cancer cells
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. 2053-2053
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. 2053-2053
    Abstract: Purpose Recent studies re-classified the c.5339T- & gt;C; p.Leu1780Pro (L1780P) BRCA1 missense mutation as “likely pathogenic” in ACMG classification, which shows high prevalence in Korean population. This study aims to reveal the molecular mechanisms and therapeutic relevance of BRCA1 L1780P mutation in DNA damaging response of triple-negative breast cancer (TNBC) cells. Method We established MDA-MB 231 and HCC1937 TNBC cell lines expressing BRCA1 wild-type and BRCA1 L1780P by stable transfection of plasmid DNAs. We performed cell proliferation assays of the TNBC cell lines with treatment of olaparib and carboplatin. We compared the protein and mRNA expression level of RAD51 in BRCA1 wild-type and L1780 transfected TNBC cell lines by western blot and RT-PCR, and BRCA1-mediated DNA damaging responses were evaluated by immunofluorescence staining of RAD51 upon olaparib and carboplatin treatment. The growth inhibitory potential of RAD51 inhibitor, RI-1 was tested in BRCA1 L1780P transfected TNBC cell lines. Results BRCA1 L1780P transfected TNBC cells showed higher migration and invasion capacity, as well as increased sensitivity to olaparib and carboplatin compared to BRCA1 wild-type transfected cells. The induction of RAD51 expression on carboplatin treatment was significantly decreased in BRCA1 L1780P TNBC cells compared with BRCA1 wild-type cells. BRCA1 L1780P transfected TNBC cells showed also showed reduced nuclear RAD51 foci formation on carboplatin and olaparib treatment. The molecular interaction between p-BRCA1 and ATM was decreased by BRCA1 L1780P introduction in TNBC cells, suggesting BRCA1 L1780P mutation disrupts binding of p-BRCA1-ATM. In a cell proliferation assay, BRCA1 L1780P transfected TNBC cells were highly sensitive to RAD51 inhibitor (IC50 = 4.15μM). Conclusion This study shows BRCA1 L1780P mutation causes defects in DNA damage responses of TNBC cells by disrupting molecular interaction between p-BRCA1 and ATM, resulting in RAD51 downregulation. The combinatory inhibition of RAD51 and PARP is a candidate strategy for TNBCs with BRCA1 L1780P mutation. Keywords: Triple-negative Breast Cancer; BRCA1 L1780 Mutation; Homologous Recombination Deficiency; RAD51 Citation Format: Jeong Dong Lee, Min Hwan Kim, Yeon A Choi, Won-Ji Ryu, Hyun Ju Han, Ae Ran Choi, Tae Yeong Kim, Joo Hyuk Sohn. Molecular characterization of BRCA1c.5339T & gt;C missense mutation in DNA damage response of triple-negative breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2053.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-2053
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Abstract 4344: Consensus genomic subtypes of gastric adenocarcinoma and their therapeutic implication
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 7_Supplement ( 2023-04-04), p. 4344-4344
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 7_Supplement ( 2023-04-04), p. 4344-4344
    Abstract: Background: Gastric adenocarcinoma (GAC) is heterogeneous lethal disease in genomic and clinical level. Although the clinical relevance of genomic and molecular subtypes of GAC has been demonstrated, their translation to the clinic has been hindered by discrepancies in classification methods. We aim to examine a consensus of genomic subtypes and correlate them with clinical outcomes. Method: We collected genomic data from 2527 GAC tumors and divided the data into discovery (n = 1427) and validation sets (n = 1100). By integrating 8 previously established genomic subtype algorithms, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs) in discovery set. For validation of clinical significance of new subtypes, we constructed GAC predictor of integrated consensus subtype with 120 genes (GPICS120) and applied it to validation data set. In systematic analysis of genomic and proteomic data, we estimated potential response rate of each subtype to standard and experimental treatments such as radiation therapy, target therapy, and immunotherapy and further validated their functional significance in cell line models. Results: Among identified 6 subtypes. CGS1 is characterized by poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 showed canonical epithelial gene expression patterns. CGS3 and CGS4 are characterized by high copy number alterations and low immune activity. However, CGS3 and CGS4 are different in high HER2 activation (CGS3) and SALL4 and KRAS activation (CSG4). CGS5 has highest mutation burden and moderately high immune activity that is characteristics of MSI-high tumors. Most of CGS6 tumors are EBV-positive and shows extremely high methylation and high immune activity. Most interestingly, CSG1 is most responsive to immunotherapy while CGS3 is significantly associated with benefit of chemoradiation therapy due to high basal level ferroptosis. In addition, we also identified potential therapeutic targets for each subtype. Conclusion: Consensus subtype is robust classification system and can be the basis for pre-clinical investigation of subtype-based targeted interventions and future clinical trials. Citation Format: Yun Seong Jeong, Young-Gyu Eun, Sung Hwan Lee, Sang-Hee Kang, Sun Young Yim, Eui Hyun Kim, Joo Kyung Noh, Bo Hwa Sohn, Ju-Seog Lee. Consensus genomic subtypes of gastric adenocarcinoma and their therapeutic implication. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4344.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2023-4344
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Abstract 3897: A difference of HER-2 amplification index between luminal B and HER2 enriched subgroup
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Research Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3897-3897
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 3897-3897
    Abstract: Background: The aim of this study was to compare the HER2 gene amplification index (AI) of luminal B and HER-2 enriched breast cancers using fluorescence in situ hybridization (FISH). Methods: Out of 753 patients with breast cancer who were tested HER2 status by FISH between Jan 2004 to Dec 2009, 224 HER2 amplified patients were available for this study. HER2-amplified breast cancers constitute a heterogenous group that may be subdivided according to their ER status: HER2 amplified ER-positive breast carcinomas that fall into the luminal B group; and HER2 amplified ER-negative cancers which form a distinct molecular subtype, known as the HER2 enriched group according to hormone status by immunohistochemistry and HER2 amplification confirmed as HER2/CEP17 ratio by FISH. A difference of HER2 AI was analyzed between luminal B and HER-2 enriched group. Clinicopathologic parameters were analyzed. Results: Among the HER2 amplified patients, the proportion of luminal B and HER2 breast cancer was 53.5% (N=120) and 46.5% (N=104), respectively. Early breast cancer patients were 84.8% (N=190) and metastatic breast cancer patients were 15.2% (N=34). HER-2 AI of luminal B group and HER2 enriched group were 4.99 and 5.84 respectively, which values showed the quantitative difference statistically significant (p=0.003). However, increasing value of HER2 AI was not associated with a better overall survival or progression free survival. In luminal B group, a significant difference of HER2 AI between ER/PR +/+ subgroup and ER/PR +/- subgroup existed which were 4.02 and 5.32, respectively (p=0004). Conclusions: The HER2 AI of HER2 enriched group was higher than that of luminal B group statistically significant. It was not clear whether the extent of HER-2 amplification relates to the survival benefit of treatment in HER-2 positive breast cancer. Further research to understand how the level of HER2 amplification is related to prognosis is warranted in order to understand the breast cancer biology associated with the intrinsic subtypes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3897. doi:10.1158/1538-7445.AM2011-3897
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2011-3897
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Abstract CT151: Phase 2 study of TAS-117 in advanced solid tumors harboringphosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog gene aberrations
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 13_Supplement ( 2021-07-01), p. CT151-CT151
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 13_Supplement ( 2021-07-01), p. CT151-CT151
    Abstract: Purpose: TAS-117 is a highly potent and selective allosteric pan-v-akt murine thymoma viral oncogene homolog (Akt) inhibitor administered orally. We conducted a single-arm, single-center, phase 2 study of TAS-117 in heavily treated patients with multiple tumors refractory to systemic chemotherapy harboring phosphatidylinositol 3-kinase (PI3K)/Akt mutations using a basket trial design. Methods: Patients with gastrointestinal (GI) cancers were administered 16 mg TAS-117 daily and those with non-GI tumors were treated with 24 mg TAS-117 for 4 days followed by a 3-day rest. The study was conducted over 21-day treatment cycles. Tumors were assessed by imaging every six weeks until disease progression, intolerable toxicity, or withdrawal. The primary endpoint was the overall response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), PFS ratio, and safety and tolerability of TAS-117. This study was registered with ClinicalTrial.gov (NCT03017521). Results: A total of 13 patients were enrolled, including eight patients with non-GI cancer (breast cancer (n = 4, 31%), ovarian cancer (n = 2, 15%), endometrial cancer (n = 1, 8%), and non-small cell lung cancer (NSCLC; n = 1, 8%)) and five patients with GI cancer (colon cancer (n = 2, 15%), rectal cancer (n = 1, 8%), gastric cancer (n = 1, 8%), and gallbladder cancer (n = 1, 8%)). The median age was 53 years (range, 34-71). The Eastern Cooperative Oncology Group (ECOG) performance status was 0 in eight patients (62%), and 10 patients (77%) were treated with TAS-117 after & gt;4 lines of therapy. Twelve patients showed mutations in PIK3 catalytic subunit alpha (PIK3CA): E542K (n = 2, 15%), E545A (n = 1, 8%), E545K (n = 4, 31%), H1047R (n = 4, 31%), and Q546K (n = 1, 8%) One patient harbored an Akt1E17K mutation. The median treatment duration was 1.4 months (range, 0.4-3.2), and the median number of treatment cycles was 2 (range 1-5). The ORR was 8% (n = 1), and the DCR was 23% (n = 3). The median PFS was 1.4 months (95% confidence interval (CI): 1.2-1.6), and the median OS was 4.8 months (95% CI: 2.6-11.2 months). At the time of data-cut off in February 19, 2020, 9 patients had disease progression, 2 patients experienced adverse events, 1 patient withdrew from study, and 1 patient discontinued treatment due to physician's decision. Treatment-related adverse events (AEs) occurred in 85% of patients, and 27% (n = 3) experienced grade 3-4 AEs (grade 3 anorexia, n = 1, 9%) and hyperglycemia (grade 3, n = 1, 9%; grade 4, n = 1, 9%). Conclusion: TAS-117 showed limited anti-tumor activity and a manageable toxicity profile in patients with advanced solid tumors. Clinical efficacy was observed in patients with ovarian cancer harboring PIK3CA E545K mutations, and in those with breast cancer harboring PIK3CA H1047R and Akt1E17K mutations. Citation Format: Jii Bum Lee, Minkyu Jung, Seung Hoon Beom, Gun Min Kim, Hye Ryun Kim, Joo Hyuk Sohn, Joong Bae Ahn, Sun Young Rha, Hyun Cheol Chung. Phase 2 study of TAS-117 in advanced solid tumors harboringphosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog gene aberrations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT151.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.AM2021-CT151
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...