{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:47:37Z","timestamp":1792198057322,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["RS\u20102026\u201025483431"],"award-info":[{"award-number":["RS\u20102026\u201025483431"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["NCC2410821"],"award-info":[{"award-number":["NCC2410821"]}],"id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Germline pathogenic\/likely pathogenic (P\/LP) variants inform cancer treatment and prevention, yet real\u2010world detection patterns and downstream clinical management remain poorly characterized in East Asian hereditary cancer cohorts. This retrospective cohort study included 5829 patients with cancer who underwent germline testing at the National Cancer Center, Republic of Korea, between April 2006 and April 2023 using\n                    <jats:italic>BRCA1\/2<\/jats:italic>\n                    \u2010only testing or multigene panel testing. We examined P\/LP variant prevalence, detection patterns under the revised national reimbursement criteria, gene group\u2010stratified post\u2010test clinical management, and variant reclassification outcomes. Among 5829 patients (96.6% female; median age, 51\u2009years), 987 (16.9%) carried P\/LP variants. Detection rates differed across reimbursement criteria, with the highest rates in patients with ovarian cancer (24.2%) and those meeting multiple criteria (up to 39.3%). Among P\/LP carriers, 773 (78.3%) received at least one post\u2010test clinical action; however, action rates differed substantially across gene groups, ranging from 84.3% among\n                    <jats:italic>BRCA1\/2<\/jats:italic>\n                    carriers to 46.0% among mismatch repair gene carriers. Of 1384 initial variants of uncertain significance, 25 (1.8%) were reclassified as P\/LP, identifying 46 additional carriers. Overall variant frequencies were strongly shaped by the breast and ovarian cancer\u2013predominant cohort composition, whereas documented post\u2010test clinical actions varied across gene groups. Variant reclassification identified additional P\/LP carriers, supporting the need for structured recontact and follow\u2010up pathways.\n                  <\/jats:p>","DOI":"10.1111\/cas.70562","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:34:18Z","timestamp":1792197258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real\u2010World Germline Variant Landscape and Clinical Management in Korean Patients Tested for Suspected Hereditary Cancer"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6991-863X","authenticated-orcid":false,"given":"Min\u2010Chae","family":"Kang","sequence":"first","affiliation":[{"name":"Targeted Therapy Branch National Cancer Center  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3616-0508","authenticated-orcid":false,"given":"Ha\u2010Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Targeted Therapy Branch National Cancer Center  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8325-6009","authenticated-orcid":false,"given":"Sang\u2010Yoon","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Gynecologic Cancer National Cancer Center  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7576-1512","authenticated-orcid":false,"given":"Seeyoun","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Breast Cancer National Cancer Center  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4508-4522","authenticated-orcid":false,"given":"So\u2010Youn","family":"Jung","sequence":"additional","affiliation":[{"name":"Center for Breast Cancer National Cancer Center  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8964-7158","authenticated-orcid":false,"given":"Myong Cheol","family":"Lim","sequence":"additional","affiliation":[{"name":"Center for Gynecologic Cancer National Cancer Center  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0609-4293","authenticated-orcid":false,"given":"Han\u2010Sung","family":"Kang","sequence":"additional","affiliation":[{"name":"Center for Breast Cancer National Cancer Center  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8470-7633","authenticated-orcid":false,"given":"Chang Ahn","family":"Seol","sequence":"additional","affiliation":[{"name":"GC Genome  Yongin\u2010si Republic of Korea"},{"name":"GC Labs  Yongin\u2010si Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4972-2306","authenticated-orcid":false,"given":"Jun\u2010Ha","family":"Jang","sequence":"additional","affiliation":[{"name":"Targeted Therapy Branch National Cancer Center  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3786-4403","authenticated-orcid":false,"given":"Sang Myung","family":"Woo","sequence":"additional","affiliation":[{"name":"Research Institute National Cancer Center  Goyang Republic of Korea"},{"name":"Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy National Cancer Center  Goyang Republic of Korea"},{"name":"Center for Liver and Pancreatobiliary Cancer National Cancer Center  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7971-211X","authenticated-orcid":false,"given":"Jae Young","family":"Joung","sequence":"additional","affiliation":[{"name":"Center for Prostate Cancer National Cancer Center  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8292-3903","authenticated-orcid":false,"given":"Wonyoung","family":"Choi","sequence":"additional","affiliation":[{"name":"Center for Rare Cancers National Cancer Center  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3949-7862","authenticated-orcid":false,"given":"Sung Chan","family":"Park","sequence":"additional","affiliation":[{"name":"Center for Colorectal Cancer National Cancer Center  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0620-4058","authenticated-orcid":false,"given":"Sun\u2010Young","family":"Kong","sequence":"additional","affiliation":[{"name":"Targeted Therapy Branch National Cancer Center  Goyang Republic of Korea"},{"name":"Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy National Cancer Center  Goyang Republic of Korea"},{"name":"Department of Laboratory Medicine National Cancer Center  Goyang Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"issue":"2","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.5306\/wjco.v14.i2.40","article-title":"Hereditary Cancer Syndromes","volume":"14","author":"Imyanitov E. N.","year":"2023","journal-title":"World Journal of Clinical Oncology"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.ygyno.2022.12.012","article-title":"Beyond BRCA: Patterns of Risk\u2010Reducing Surgery for Non\u2010BRCA, Homologous Recombination Repair Pathway Gene Variant Carriers","volume":"170","author":"Lee S. S.","year":"2023","journal-title":"Gynecologic Oncology"},{"issue":"3","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/cncr.32572","article-title":"Clinical Utility of Hereditary Cancer Panel Testing: Impact of PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and RAD51D Results on Patient Management and Adherence to Provider Recommendations","volume":"126","author":"Vysotskaia V.","year":"2020","journal-title":"Cancer"},{"issue":"3","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.ygyno.2016.01.019","article-title":"Genetic Testing for Hereditary Cancer Predisposition: BRCA1\/2, Lynch Syndrome, and Beyond","volume":"140","author":"Hall M. J.","year":"2016","journal-title":"Gynecologic Oncology"},{"issue":"11","key":"e_1_2_11_6_1","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2024.44526","article-title":"Clinical Variant Reclassification in Hereditary Disease Genetic Testing","volume":"7","author":"Kobayashi Y.","year":"2024","journal-title":"JAMA Network Open"},{"issue":"1","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13073-020-00744-3","article-title":"Ancestry\u2010Specific Predisposing Germline Variants in Cancer","volume":"12","author":"Oak N.","year":"2020","journal-title":"Genome Medicine"},{"key":"e_1_2_11_8_1","volume-title":"Scope of Accreditation on BRCA (BRCA1, BRCA2) Gene Mutation Test","author":"Health Insurance Review & Assessment Service","year":"2012"},{"key":"e_1_2_11_9_1","volume-title":"Notification No. 2020\u2010135 of the Ministry of Health and Welfare","author":"Ministry of Health and Welfare","year":"2020"},{"issue":"5","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards S.","year":"2015","journal-title":"Genetics in Medicine"},{"issue":"11","key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1038\/s41588-021-00949-1","article-title":"The Context\u2010Specific Role of Germline Pathogenicity in Tumorigenesis","volume":"53","author":"Srinivasan P.","year":"2021","journal-title":"Nature Genetics"},{"key":"e_1_2_11_12_1","unstructured":"National Comprehensive Cancer Network \u201cGenetic\/Familial High\u2010Risk Assessment: Breast Ovarian Pancreatic and Prostate Version 3.2026 \u201dhttps:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/genetics_bop.pdf."},{"issue":"8","key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/gim.2015.166","article-title":"Pathogenic and Likely Pathogenic Variant Prevalence Among the First 10,000 Patients Referred for Next\u2010Generation Cancer Panel Testing","volume":"18","author":"Susswein L. R.","year":"2016","journal-title":"Genetics in Medicine"},{"issue":"2","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/s41436-019-0633-8","article-title":"A Clinical Guide to Hereditary Cancer Panel Testing: Evaluation of Gene\u2010Specific Cancer Associations and Sensitivity of Genetic Testing Criteria in a Cohort of 165,000 High\u2010Risk Patients","volume":"22","author":"LaDuca H.","year":"2020","journal-title":"Genetics in Medicine"},{"issue":"6","key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1002\/cncr.34056","article-title":"Prevalence and Spectrum of Pathogenic Variants Among Patients With Multiple Primary Cancers Evaluated by Clinical Characteristics","volume":"128","author":"Bychkovsky B. L.","year":"2022","journal-title":"Cancer"},{"issue":"3","key":"e_1_2_11_16_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.esmoop.2025.104495","article-title":"Pathogenic Germline Variants in Cancer Predisposition Genes in Patients With Multiple Primary Cancers in an Asian Population and the Role of Extended Panel Genetic Testing","volume":"10","author":"Cheo S. W.","year":"2025","journal-title":"ESMO Open"},{"issue":"9","key":"e_1_2_11_17_1","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1001\/jamaoncol.2017.0424","article-title":"Associations Between Cancer Predisposition Testing Panel Genes and Breast Cancer","volume":"3","author":"Couch F. 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R.","year":"2020","journal-title":"Journal of the National Cancer Institute"},{"issue":"35","key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"3918","DOI":"10.1200\/JCO.21.00640","article-title":"Germline Pathogenic Variants in Cancer Predisposition Genes Among Women With Invasive Lobular Carcinoma of the Breast","volume":"39","author":"Yadav S.","year":"2021","journal-title":"Journal of Clinical Oncology"},{"issue":"15","key":"e_1_2_11_21_1","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1200\/JCO.20.01200","article-title":"Mutations in BRCA1\/2 and Other Panel Genes in Patients With Metastatic Breast Cancer\u2014Association With Patient and Disease Characteristics and Effect on Prognosis","volume":"39","author":"Fasching P. A.","year":"2021","journal-title":"Journal of Clinical Oncology"},{"issue":"1","key":"e_1_2_11_22_1","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1158\/1078-0432.CCR-24-1884","article-title":"Pathogenic Variants in Cancer Susceptibility Genes Predispose to Ductal Carcinoma In\u00a0Situ of the Breast","volume":"31","author":"Huang H.","year":"2025","journal-title":"Clinical Cancer Research"},{"issue":"1","key":"e_1_2_11_23_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-025-95834-w","article-title":"Comprehensive Germline and Somatic Profiling of High\u2010Risk Thai Breast Cancer via Next\u2010Generation Sequencing","volume":"15","author":"Kamdee K.","year":"2025","journal-title":"Scientific Reports"},{"issue":"4","key":"e_1_2_11_24_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers12040956","article-title":"Multigene Panel Germline Testing of 1333 Czech Patients With Ovarian Cancer","volume":"12","author":"Lhotova K.","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"10","key":"e_1_2_11_25_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.gim.2024.101230","article-title":"Extended Panel Testing in Ovarian Cancer Reveals BRIP1 as the Third Most Important Predisposition Gene","volume":"26","author":"Morgan R. D.","year":"2024","journal-title":"Genetics in Medicine"},{"key":"e_1_2_11_26_1","doi-asserted-by":"crossref","DOI":"10.1200\/GO.22.00104","article-title":"Germline Pathogenic Variant Prevalence Among Latin American and US Hispanic Individuals Undergoing Testing for Hereditary Breast and Ovarian Cancer: A Cross\u2010Sectional Study","volume":"8","author":"Ossa Gomez C. A.","year":"2022","journal-title":"JCO Global Oncology"},{"issue":"12","key":"e_1_2_11_27_1","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1093\/jnci\/djaa030","article-title":"Ovarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D","volume":"112","author":"Yang X.","year":"2020","journal-title":"Journal of the National Cancer Institute"},{"issue":"12","key":"e_1_2_11_28_1","doi-asserted-by":"crossref","first-page":"3952","DOI":"10.1111\/cas.16367","article-title":"Prevalence and Outcomes of Germline Pathogenic Variants of Homologous Recombination Repair Genes in Ovarian Cancer","volume":"115","author":"Miwa M.","year":"2024","journal-title":"Cancer Science"},{"issue":"1","key":"e_1_2_11_29_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12885-022-10456-z","article-title":"Clinical Characteristics and Survival Analysis of Chinese Ovarian Cancer Patients With RAD51D Germline Mutations","volume":"22","author":"Yao H.","year":"2022","journal-title":"BMC Cancer"},{"issue":"2","key":"e_1_2_11_30_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s10549-018-5015-4","article-title":"Prevalence and Oncologic Outcomes of BRCA 1\/2 Mutations in Unselected Triple\u2010Negative Breast Cancer Patients in Korea","volume":"173","author":"Ryu J. M.","year":"2019","journal-title":"Breast Cancer Research and Treatment"},{"issue":"31","key":"e_1_2_11_31_1","doi-asserted-by":"crossref","first-page":"3660","DOI":"10.1200\/JCO.2015.63.0996","article-title":"American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility","volume":"33","author":"Robson M. E.","year":"2015","journal-title":"Journal of Clinical Oncology"},{"issue":"18","key":"e_1_2_11_32_1","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1200\/JCO.20.00299","article-title":"Management of Hereditary Breast Cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Guideline","volume":"38","author":"Tung N. M.","year":"2020","journal-title":"Journal of Clinical Oncology"},{"key":"e_1_2_11_33_1","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2022.867226","article-title":"The Impact of Proband Indication for Genetic Testing on the Uptake of Cascade Testing Among Relatives","volume":"13","author":"Schmidlen T. J.","year":"2022","journal-title":"Frontiers in Genetics"},{"issue":"2","key":"e_1_2_11_34_1","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1001\/jamaoncol.2020.6252","article-title":"Comparison of Universal Genetic Testing vs Guideline\u2010Directed Targeted Testing for Patients With Hereditary Cancer Syndrome","volume":"7","author":"Samadder N. J.","year":"2021","journal-title":"JAMA Oncology"},{"issue":"2","key":"e_1_2_11_35_1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s10689-024-00360-9","article-title":"Cascade Screening in HBOC and Lynch Syndrome: Guidelines and Procedures in a UK Centre","volume":"23","author":"Evans D. G.","year":"2024","journal-title":"Familial Cancer"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70562","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.70562","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70562","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:34:23Z","timestamp":1792197263000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.70562"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,16]]},"references-count":34,"alternative-id":["10.1111\/cas.70562"],"URL":"https:\/\/doi.org\/10.1111\/cas.70562","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,16]]},"assertion":[{"value":"2026-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cas.70562"}}