{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:27:24Z","timestamp":1791044844009,"version":"4.1.0"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"JOHBOC"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Considering past research in Europe and the USA, the conditions for medical insurance coverage of <jats:italic>BRCA1\/2<\/jats:italic> genetic testing (GT) in Japan have been established as follows: 1. Breast cancer onset at 45\u00a0years or younger age; 2. Triple-negative breast cancer (TNBC) onset at 60\u00a0years or younger age; 3. Onset of two or more primary breast cancers; 4. Family history of breast cancer, ovarian cancer, or pancreatic cancer up to the third degree; 5. Male breast cancer, 6. Ovarian, fallopian, or peritoneal cancers. However, data to determine the importance and extent of each factor in the current conditions are insufficient. Consequently, this study aimed to assess the validity of insurance coverage conditions in Japan, elucidate the relationship between these conditions, and explore the possibility of proposing new indicators.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>A total of 5987 breast cancer patients were enrolled from 92 centers participating in the HBOC consortium and the JOHBOC registry project. Of these, 5904 patients were analyzed after excluding 48 male breast cancer patients due to insufficient numbers for analysis and 35 patients whose age at breast cancer onset was unknown or unregistered. We compared 1,091 cases in which pathogenic variants (PVs) (<jats:italic>BRCA1<\/jats:italic>(B1s): 543, <jats:italic>BRCA2<\/jats:italic>(B2s): 548) were detected with 4580 cases in which no variants (non-Vs) were detected. Variants of uncertain significance (VUS: 233 cases) were not classified as either PVs or non-Vs for subsequent analysis. We investigated the validity of each condition under which an HBOC diagnosis could be considered for medical insurance coverage.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Regardless of the insurance coverage conditions, the detection rate of pathogenic variants (DRPV) of all analyzed cases was 19.2%. The DRPV under the insurance coverage conditions for GT\u2014\u2018Age of breast cancer onset\u2009\u2264\u200945\u00a0years,\u2019 \u2018TNBC onset at\u2009\u2264\u200960\u00a0years,\u2019 \u2018\u2009\u2265\u20092 primary breast cancers,\u2019 \u2018Patients with breast cancer concurrent with ovarian cancer,\u2019 and \u2018\u2009\u2265\u20091 family history of breast or ovarian cancer up to the third degree\u2019\u2014was 25.4%, 31.6%, 24.6%, 48.8%, and 25.6%, respectively. Those within the insurance coverage group showed a pathogenic variant detection rate of 21.1%, compared to only 5.6% outside of the coverage. Our analysis indicates that medical insurance coverage conditions effectively identify candidates for GT. Furthermore, when examining the number of conditions met and the positivity rate, the positivity rate was 11.2%, with only one condition met. This rate increases exponentially as more conditions are met, underscoring the importance of multiple matching conditions. Additionally, those with comorbid ovarian cancer or a family history of ovarian cancer are more likely to have a pathogenic variant. Additionally, we reevaluated cases who did not meet the medical insurance conditions. TNBC occurrence was significantly associated with B1s, even when restricted to onset age\u2009\u2265\u200961\u00a0years. Familial history of prostate cancer also significantly associated with B2s.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This study determined that the Japanese medical insurance coverage conditions effectively identified candidates eligible for GT. Consequently, it is imperative to disseminate information to all patients with breast cancer covered by insurance, emphasizing the opportunity for GT, particularly if they have ovarian cancer complications or a family history of ovarian cancer.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s12282-025-01704-8","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T11:28:00Z","timestamp":1746444480000},"page":"792-802","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Analysis of the conditions for applying BRCA genetic testing to women with breast cancer using the Japanese HBOC consortium and the Japanese organization of hereditary breast and ovarian cancer (JOHBOC) registry project database"],"prefix":"10.1007","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6641-9598","authenticated-orcid":false,"given":"Masato","family":"Takahashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1926-2927","authenticated-orcid":false,"given":"Yuko","family":"Minoura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2530-3804","authenticated-orcid":false,"given":"Hiroki","family":"Den","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Nomizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4565-4721","authenticated-orcid":false,"given":"Takanori","family":"Ishida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiraku","family":"Kumamaru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7544-4536","authenticated-orcid":false,"given":"Masami","family":"Arai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6597-9107","authenticated-orcid":false,"given":"Seigo","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"key":"1704_CR1","doi-asserted-by":"publisher","first-page":"2402","DOI":"10.1001\/jama.2017.7112","volume":"317","author":"KB Kuchenbaecker","year":"2017","unstructured":"Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. JAMA. 2017;317:2402\u201316.","journal-title":"JAMA"},{"key":"1704_CR2","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1007\/s12282-020-01148-2","volume":"28","author":"R Yoshida","year":"2021","unstructured":"Yoshida R. Hereditary breast and ovarian cancer (HBOC): review of its molecular characteristics, screening, treatment, and prognosis. Breast Cancer. 2021;28:1167\u201380.","journal-title":"Breast Cancer"},{"key":"1704_CR3","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1007\/s12282-017-0803-y","volume":"25","author":"H Yamauchi","year":"2018","unstructured":"Yamauchi H, Nakagawa C, Kobayashi M, Kobayashi Y, Mano T, Nakamura S, et al. Cost-effectiveness of surveillance and prevention strategies in BRCA1\/2 mutation carriers. Breast Cancer. 2018;25:141\u201350.","journal-title":"Breast Cancer"},{"key":"1704_CR4","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1001\/jamasurg.2023.4770","volume":"158","author":"G Martelli","year":"2023","unstructured":"Martelli G, Barretta F, Vernieri C, Folli S, Pruneri G, Segattini S, et al. Prophylactic Salpingo-Oophorectomy and Survival After BRCA1\/2 Breast Cancer Resection. JAMA Surg. 2023;158:1275\u201384.","journal-title":"JAMA Surg"},{"key":"1704_CR5","doi-asserted-by":"publisher","first-page":"4083","DOI":"10.1038\/s41467-018-06581-8","volume":"9","author":"Y Momozawa","year":"2018","unstructured":"Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, et al. Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. Nat Commun. 2018;9:4083.","journal-title":"Nat Commun"},{"key":"1704_CR6","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1136\/ijgc-2019-000384","volume":"29","author":"T Enomoto","year":"2019","unstructured":"Enomoto T, Aoki D, Hattori K, Jinushi M, Kigawa J, Takeshima N, et al. The first Japanese nationwide multicenter study of BRCA mutation testing in ovarian cancer: CHARacterizing the cross-sectional approach to Ovarian cancer geneTic TEsting of BRCA (CHARLOTTE). Int J Gynecol Cancer. 2019;29:1043\u20139.","journal-title":"Int J Gynecol Cancer"},{"key":"1704_CR7","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s10549-014-3100-x","volume":"147","author":"T Byrski","year":"2014","unstructured":"Byrski T, Huzarski T, Dent R, Marczyk E, Jasiowka M, Gronwald J, et al. Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat. 2014;147:401\u20135.","journal-title":"Breast Cancer Res Treat"},{"key":"1704_CR8","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/S0140-6736(10)60892-6","volume":"376","author":"A Tutt","year":"2010","unstructured":"Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, et al. Oral poly (ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010;376:235\u201344.","journal-title":"Lancet"},{"key":"1704_CR9","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.1056\/NEJMoa2105215","volume":"384","author":"ANJ Tutt","year":"2021","unstructured":"Tutt ANJ, Garber JE, Kaufman B, Viale G, Fumagalli D, Rastogi P, et al. Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer. N Engl J Med. 2021;384:2394\u2013405.","journal-title":"N Engl J Med"},{"key":"1704_CR10","unstructured":"NCCN.org: Genetic\/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. NCCN Guideline ver. 3, 2024"},{"key":"1704_CR11","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/s10038-023-01163-z","volume":"68","author":"K Muto","year":"2023","unstructured":"Muto K, Nagai A, Ri I, Takashima K, Yoshida S. Is legislation to prevent genetic discrimination necessary in Japan? An overview of the current policies and public attitudes. J Hum Genet. 2023;68:579\u201385.","journal-title":"J Hum Genet"},{"key":"1704_CR12","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1007\/s10198-019-01038-1","volume":"20","author":"D M\u00fcller","year":"2019","unstructured":"M\u00fcller D, Danner M, Schmutzler R, Engel C, Wassermann K, Stollenwerk B, et al. Economic modeling of risk-adapted screen-and-treat strategies in women at high risk for breast or ovarian cancer. Eur J Health Econ. 2019;20:739\u201350.","journal-title":"Eur J Health Econ"},{"key":"1704_CR13","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1001\/jamaoncol.2015.3048","volume":"1","author":"J Armstrong","year":"2015","unstructured":"Armstrong J, Toscano M, Kotchko N, Friedman S, Schwartz MD, Virgo KS, et al. Utilization and outcomes of BRCA genetic testing and counseling in a national commercially insured population: the ABOUT study. JAMA Oncol. 2015;1:1251\u201360.","journal-title":"JAMA Oncol"},{"key":"1704_CR14","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.annonc.2022.10.004","volume":"34","author":"C Sessa","year":"2023","unstructured":"Sessa C, Balma\u00f1a J, Bober SL, Cardoso MJ, Colombo N, Curigliano G, et al. Risk reduction and screening of cancer in hereditary breast\u2013 ovarian cancer syndromes: ESMO clinical practice guideline. Ann Oncol. 2023;34:33\u201347.","journal-title":"Ann Oncol"},{"key":"1704_CR15","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1001\/jamaoncol.2023.6937","volume":"10","author":"J Kotsopoulos","year":"2024","unstructured":"Kotsopoulos J, Gronwald J, Huzarski T, M\u00f8ller P, Pal T, McCuaig JM, et al. Bilateral oophorectomy and all-cause mortality in women with BRCA1 and BRCA2 sequence variations. JAMA Oncol. 2024;10:484\u201392.","journal-title":"JAMA Oncol"},{"key":"1704_CR16","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1007\/s12282-022-01360-2","volume":"29","author":"Y Minoura","year":"2022","unstructured":"Minoura Y, Takahashi M, Maeda H, Kuwahara S, Tachikawa H, Yamamoto M, et al. Significance of prostate\/pancreatic\/skin cancer family history for detecting BRCA2 pathogenic variant careers among patients with breast cancer. Breast Cancer. 2022;29:808\u201313.","journal-title":"Breast Cancer"},{"key":"1704_CR17","doi-asserted-by":"publisher","first-page":"2243","DOI":"10.1056\/NEJMsr1501341","volume":"372","author":"DF Easton","year":"2015","unstructured":"Easton DF, Pharoah PD, Antoniou AC, Tischkowitz M, Tavtigian SV, Nathanson KL, et al. Gene-panel sequencing and the prediction of breast-cancer risk. N Engl J Med. 2015;372:2243\u201357.","journal-title":"N Engl J Med"}],"container-title":["Breast Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12282-025-01704-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12282-025-01704-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12282-025-01704-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T12:44:37Z","timestamp":1750164277000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12282-025-01704-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,5]]},"references-count":17,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["1704"],"URL":"https:\/\/doi.org\/10.1007\/s12282-025-01704-8","relation":{},"ISSN":["1340-6868","1880-4233"],"issn-type":[{"value":"1340-6868","type":"print"},{"value":"1880-4233","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,5]]},"assertion":[{"value":"18 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Masato Takahashi received lecture fees or honoraria from Astra Zeneca, Daiichi Sankyo, Eisai, Eli Lilly, MSD and Pfizer. Tadanori Ishida received lecture fees or honoraria from Astra Zeneca. Other authors declare that there is no conflict of interest..","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}