{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:21:30Z","timestamp":1790061690705,"version":"4.0.1"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2015,7,11]],"date-time":"2015-07-11T00:00:00Z","timestamp":1436572800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2015,7,11]],"date-time":"2015-07-11T00:00:00Z","timestamp":1436572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Breast Cancer Res"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>Mammographic density (MD) is one of the strongest determinants of sporadic breast cancer (BC). In this study, we compared MD in <jats:italic>BRCA1\/2<\/jats:italic> mutation carriers and non-carriers from <jats:italic>BRCA1\/2<\/jats:italic> mutation-positive families and investigated the association between MD and BC among <jats:italic>BRCA1\/2<\/jats:italic> mutation carriers per type of mutation and tumor subtype.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>The study was carried out in 1039 female members of <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> mutation-positive families followed at 16 Spanish Genetic Counseling Units. Participants\u2019 density was scored retrospectively from available mammograms by a single blinded radiologist using a 5-category scale (&lt;10 %, 10-25 %, 25-50 %, 50-75 %, &gt;75 %). In BC cases, we selected mammograms taken prior to diagnosis or from the contralateral breast, whereas, in non-cases, the last screening mammogram was evaluated. MD distribution in carriers and non-carriers was compared using ordinal logistic models, and the association between MD and BC in <jats:italic>BRCA1\/2<\/jats:italic> mutation carriers was studied using logistic regression. Huber-White robust estimators of variance were used to take into account correlations between family members. A similar multinomial model was used to explore this association by BC subtype.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>We identified and scored mammograms from 341 <jats:italic>BRCA1<\/jats:italic>, 350 <jats:italic>BRCA2<\/jats:italic> mutation carriers and 229 non-carriers. Compared to non-carriers, MD was significantly lower among <jats:italic>BRCA2<\/jats:italic> mutation carriers (odds ratio (OR) =0.71; <jats:italic>P-<\/jats:italic>value=0.04), but not among <jats:italic>BRCA1<\/jats:italic> carriers (OR=0.84; <jats:italic>P-<\/jats:italic>value=0.33). MD was associated with subsequent development BC (OR per category of MD=1.45; 95 % confidence interval=1.18-1.78, <jats:italic>P-<\/jats:italic>value&lt;0.001), with no significant differences between <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> mutation carriers (<jats:italic>P-<\/jats:italic>value=0.48). Finally, no statistically significant differences were observed in the association of MD with specific BC subtypes.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Our study, the largest to date on this issue, confirms that MD is an independent risk factor for all BC subtypes in either <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> mutation carriers, and should be considered a phenotype risk marker in this context.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/s13058-015-0604-1","type":"journal-article","created":{"date-parts":[[2015,7,10]],"date-time":"2015-07-10T15:17:17Z","timestamp":1436541437000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Mammographic density and breast cancer in women from high risk families"],"prefix":"10.1186","volume":"17","author":[{"given":"Teresa","family":"Ram\u00f3n y Cajal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Chirivella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefa","family":"Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Teule","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Izquierdo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Balma\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Beatriz","family":"S\u00e1nchez-Heras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Llort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Fisas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Lope","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Hern\u00e1ndez-Agudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Juan-Fita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Tena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Robles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Guill\u00e9n-Ponce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"P\u00e9rez-Segura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari Sol","family":"Luque-Molina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Hernando-Polo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Salinas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Brunet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Dolores","family":"Salas-Trejo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agust\u00ed","family":"Barnadas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Poll\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,7,11]]},"reference":[{"key":"604_CR1","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1158\/1055-9965.EPI-06-0034","volume":"15","author":"VA McCormack","year":"2006","unstructured":"McCormack VA, dos Santos Silva I. 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