{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T01:34:42Z","timestamp":1768440882164,"version":"3.49.0"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,16]],"date-time":"2019-01-16T00:00:00Z","timestamp":1547596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Ductal carcinoma in situ (DCIS) is considered a component of the clinical spectrum of breast cancer even in those with <jats:italic>BRCA1\/2<\/jats:italic> mutation. The aim of this study was to report the feature of DCIS raised in Japanese women with <jats:italic>BRCA1\/2<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 325 Japanese women with breast cancer (BC) (with or without invasive cancer) were referred for genetic counseling and underwent genetic testing for mutations in the <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> genes in Showa University Hospital between December 2011 and August 2016. And 49 of them who were pathologically diagnosed as DCIS were included in this study. Logistic regression models were fit to determine the associations between potential predictive factors and <jats:italic>BRCA<\/jats:italic> status. A Cox proportional hazards model is used to predictive value of parameters for Ipsilateral breast tumor recurrence (IBTR) and contralateral breast tumor recurrence (CBTR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>(a) Of 325 patients (with or without invasive cancer), 19.1% (62\/325) tested positive for <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>BRCA2<\/jats:italic> mutations. And 18.4% (9\/49) was positive for <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>BRCA2<\/jats:italic> mutations in DCIS, compared with 19.2% (53\/276) in IDC (<jats:italic>p\u00a0<\/jats:italic>=\u00a01.000). Among <jats:italic>BRCA<\/jats:italic> mutations, 14.5% (9\/62) had DCIS compared with nonmutations (15.2%, 40\/263). Incidence of DCIS was 3.0% (1\/33) of <jats:italic>BRCA1<\/jats:italic> mutations and 27.5% (8\/29) of <jats:italic>BRCA2<\/jats:italic> mutation (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.009). (b) Median age of diagnosis in <jats:italic>BRCA<\/jats:italic> mutation carriers was 39\u00a0years, compared with 46\u00a0years in noncarriers. Age, Family history (FH) of BC, FH of first or second BC and total number of relatives with BC diagnosis (DX) has significant difference between <jats:italic>BRCA<\/jats:italic> mutation carriers and noncarriers in univariate analysis. In a multivariate logistic model, total relatives with BC DX\u00a0\u2265\u00a02 (odds ratio [OR], 5.128; 95% confidence interval [CI], 1.266\u201320.763; <jats:italic>p\u00a0<\/jats:italic>=\u00a00.022), age at diagnosis \u226435\u00a0years (OR 0.149, 95% CI 0.023\u20130.954, <jats:italic>p\u00a0<\/jats:italic>=\u00a00.045) and ER+\/HER2+ status (OR 5.034, 95% CI 1.092\u201323.210, <jats:italic>p\u00a0<\/jats:italic>=\u00a00.038) remained as independent significant predictors for <jats:italic>BRCA<\/jats:italic> mutation. Ki67 index (cut off by 14% or 30%) did not differ between <jats:italic>BRCA<\/jats:italic> mutation carriers and noncarriers (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.459 and <jats:italic>p\u00a0<\/jats:italic>=\u00a00.651). (c) There was a significant difference in ER\u2010positive tumors among <jats:italic>BRCA2<\/jats:italic> carriers and noncarriers (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.042). Subgroup analysis showed <jats:italic>BRCA2<\/jats:italic> carriers tend to be of higher grade (Grade 2 and 3), more frequently ER+\/PR+ (<jats:italic>p\u00a0<\/jats:italic>=\u00a00.041) and lower proliferation (Ki67 index) than noncarriers, whereas differences in nuclear grade and ki67 index were not found significantly in our study. (d) <jats:italic>BRCA<\/jats:italic> mutation was not associated with an increased risk of IBTR and CBTR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>DCIS is equally as prevalent in patients who were <jats:italic>BRCA<\/jats:italic> mutation carriers as in high familial\u2010risk women who were noncarriers, but occurs at earlier age. <jats:italic>BRCA2<\/jats:italic> carriers have higher incidence in DCIS than that of <jats:italic>BRCA1<\/jats:italic> carriers, and tend to be higher grade and more frequently ER positive and lower proliferation. Total relatives with BC DX \u22652, age at diagnosis \u226435\u00a0years and ER+\/HER2+ might be independent predictors for <jats:italic>BRCA<\/jats:italic> mutation in Japanese women with DCIS and patients of these risk factors should be recommended to receive genetic counseling and <jats:italic>BRCA<\/jats:italic> testing.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.493","type":"journal-article","created":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T05:23:40Z","timestamp":1547702620000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<i>BRCA1\/BRCA2<\/i> mutations in Japanese women with ductal carcinoma in situ"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7547-8699","authenticated-orcid":false,"given":"Yan","family":"Liu","sequence":"first","affiliation":[{"name":"The 3rd Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Tianjin China"},{"name":"Key Laboratory of Breast Cancer Prevention and Therapy of Ministry of Education Tianjin China"},{"name":"Key Laboratory of Cancer Prevention and Therapy Tianjin China"},{"name":"Tianjin's Clinical Research Center for Cancer Tianjin China"},{"name":"Division of Breast Surgical Oncology, Department of Surgery Showa University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshimi","family":"Ide","sequence":"additional","affiliation":[{"name":"Division of Breast Surgical Oncology, Department of Surgery Showa University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayuko","family":"Inuzuka","sequence":"additional","affiliation":[{"name":"Division of Breast Surgical Oncology, Department of Surgery Showa University School of Medicine Tokyo 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