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dc.contributor.authorTryggvadottir, Laufey
dc.contributor.authorOlafsdottir, Elinborg J
dc.contributor.authorOlafsdottir, Gudridur H
dc.contributor.authorSigurdsson, Helgi
dc.contributor.authorJohannsson, Oskar T
dc.contributor.authorBjorgvinsson, Einar
dc.contributor.authorAlexiusdottir, Kristin
dc.contributor.authorStefansson, Olafur A
dc.contributor.authorAgnarsson, Bjarni A
dc.contributor.authorNarod, Steven A
dc.contributor.authorEyfjord, Jorunn E
dc.contributor.authorJonasson, Jon G
dc.date.accessioned2014-08-12T15:26:25Z
dc.date.available2014-08-12T15:26:25Z
dc.date.issued2013-07
dc.date.submitted2013
dc.identifier.citationBreast Cancer Res. 2013, 140 (2):375-84en
dc.identifier.issn1573-7217
dc.identifier.pmid23857704
dc.identifier.doi10.1007/s10549-013-2637-4
dc.identifier.urihttp://hdl.handle.net/2336/324725
dc.descriptionTo access publisher's full text version of this article click on the hyperlink at the bottom of the pageen
dc.description.abstractIt is not well known to what extent carrying a BRCA2 mutation affects the survival of women with breast cancer and prognostic factors among BRCA2-positive women warrant investigation. Using a record linkage approach we compared the long-term survival in carriers and noncarriers of an inherited BRCA2 founder mutation (999del5), and sought to identify prognostic factors among the BRCA2 mutation-positive subset, including markers of genetic instability (aneuploidy) and mitotic activity (S-phase fraction). We established the genetic status of 2,967 Icelandic breast cancer patients (215 mutation carriers and 2,752 noncarriers) diagnosed from 1955 to 2004, representing 72 % of all cases diagnosed in the country during this period. Tumour ploidy and S-phase fraction were assessed on tumour cells by DNA flow cytometry. Prognostic factors were assessed blindly with respect to mutation status. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival by BRCA2 status, using Cox regression. After a median follow-up of 9.5 years, BRCA2 mutation carriers had a higher risk of death from breast cancer than noncarriers (HR 1.64, 95 % CI 1.24-2.16, p < 0.001). The risk increase was restricted to women with diploid tumours (HR 3.03, 95 % CI 1.91-4.79, p < 0.001). Among breast cancer patients with aneuploid tumours, survival of carriers was similar to that of noncarriers (HR 0.76, 95 % CI 0.41-1.41, p = 0.38). Increased tumour size and a positive nodal status predicted worse prognosis in all patients, whereas the highly correlated prognostic factors diploidy, low proliferative activity and a positive estrogen receptor status had reverse effects in mutation carriers and noncarriers. Breast cancer patients who carry the Icelandic founder BRCA2 mutation have inferior long-term survival than noncarriers, but the adverse prognosis is restricted to mutation carriers with diploid, slowly proliferating tumours.
dc.description.sponsorshipIcelandic Cancer Society US Army Medical Research Acquisition Activity DAMD17-97-1-7002 DAMD17-99-1-9216en
dc.language.isoenen
dc.publisherSpringeren
dc.relation.urlhttp://dx.doi.org/10.1007/s10549-013-2637-4en
dc.relation.urlhttp://download.springer.com/static/pdf/167/art%253A10.1007%252Fs10549-013-2637-4.pdf?auth66=1408029833_986ba3b6b15752594e26e2a1e6f654fe&ext=.pdfen
dc.rightsArchived with thanks to Breast cancer research and treatmenten
dc.subjectBrjóstakrabbameinen
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshBRCA2 Proteinen
dc.subject.meshBreast Neoplasmsen
dc.subject.meshDiploidyen
dc.subject.meshFemaleen
dc.subject.meshHumansen
dc.subject.meshMiddle Ageden
dc.subject.meshMutationen
dc.subject.meshPrognosisen
dc.subject.meshSurvival Analysisen
dc.titleTumour diploidy and survival in breast cancer patients with BRCA2 mutations.en
dc.typeArticleen
dc.contributor.departmentIceland Canc Soc, Iceland Canc Registry, IS-125 Reykjavik, Iceland, Univ Iceland, Fac Med, Reykjavik, Iceland, Landspitali Univ Hosp, Dept Oncol, Reykjavik, Iceland, Univ Iceland, Canc Res Lab, Biomed Ctr, Sch Hlth Sci, Reykjavik, Iceland, Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland, Univ Toronto, Womens Coll, Res Inst, Toronto, ON, Canadaen
dc.identifier.journalBreast cancer research and treatmenten
dc.rights.accessNational Consortium - Landsaðganguren
html.description.abstractIt is not well known to what extent carrying a BRCA2 mutation affects the survival of women with breast cancer and prognostic factors among BRCA2-positive women warrant investigation. Using a record linkage approach we compared the long-term survival in carriers and noncarriers of an inherited BRCA2 founder mutation (999del5), and sought to identify prognostic factors among the BRCA2 mutation-positive subset, including markers of genetic instability (aneuploidy) and mitotic activity (S-phase fraction). We established the genetic status of 2,967 Icelandic breast cancer patients (215 mutation carriers and 2,752 noncarriers) diagnosed from 1955 to 2004, representing 72 % of all cases diagnosed in the country during this period. Tumour ploidy and S-phase fraction were assessed on tumour cells by DNA flow cytometry. Prognostic factors were assessed blindly with respect to mutation status. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival by BRCA2 status, using Cox regression. After a median follow-up of 9.5 years, BRCA2 mutation carriers had a higher risk of death from breast cancer than noncarriers (HR 1.64, 95 % CI 1.24-2.16, p < 0.001). The risk increase was restricted to women with diploid tumours (HR 3.03, 95 % CI 1.91-4.79, p < 0.001). Among breast cancer patients with aneuploid tumours, survival of carriers was similar to that of noncarriers (HR 0.76, 95 % CI 0.41-1.41, p = 0.38). Increased tumour size and a positive nodal status predicted worse prognosis in all patients, whereas the highly correlated prognostic factors diploidy, low proliferative activity and a positive estrogen receptor status had reverse effects in mutation carriers and noncarriers. Breast cancer patients who carry the Icelandic founder BRCA2 mutation have inferior long-term survival than noncarriers, but the adverse prognosis is restricted to mutation carriers with diploid, slowly proliferating tumours.


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