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dc.contributor.authorGiardiello, Daniele
dc.contributor.authorSteyerberg, Ewout W
dc.contributor.authorHauptmann, Michael
dc.contributor.authorAdank, Muriel A
dc.contributor.authorAkdeniz, Delal
dc.contributor.authorBlomqvist, Carl
dc.contributor.authorBojesen, Stig E
dc.contributor.authorBolla, Manjeet K
dc.contributor.authorBrinkhuis, Mariël
dc.contributor.authorChang-Claude, Jenny
dc.contributor.authorCzene, Kamila
dc.contributor.authorDevilee, Peter
dc.contributor.authorDunning, Alison M
dc.contributor.authorEaston, Douglas F
dc.contributor.authorEccles, Diana M
dc.contributor.authorFasching, Peter A
dc.contributor.authorFigueroa, Jonine
dc.contributor.authorFlyger, Henrik
dc.contributor.authorGarcía-Closas, Montserrat
dc.contributor.authorHaeberle, Lothar
dc.contributor.authorHaiman, Christopher A
dc.contributor.authorHall, Per
dc.contributor.authorHamann, Ute
dc.contributor.authorHopper, John L
dc.contributor.authorJager, Agnes
dc.contributor.authorJakubowska, Anna
dc.contributor.authorJung, Audrey
dc.contributor.authorKeeman, Renske
dc.contributor.authorKramer, Iris
dc.contributor.authorLambrechts, Diether
dc.contributor.authorLe Marchand, Loic
dc.contributor.authorLindblom, Annika
dc.contributor.authorLubiński, Jan
dc.contributor.authorManoochehri, Mehdi
dc.contributor.authorMariani, Luigi
dc.contributor.authorNevanlinna, Heli
dc.contributor.authorOldenburg, Hester S A
dc.contributor.authorPelders, Saskia
dc.contributor.authorPharoah, Paul D P
dc.contributor.authorShah, Mitul
dc.contributor.authorSiesling, Sabine
dc.contributor.authorSmit, Vincent T H B M
dc.contributor.authorSouthey, Melissa C
dc.contributor.authorTapper, William J
dc.contributor.authorTollenaar, Rob A E M
dc.contributor.authorvan den Broek, Alexandra J
dc.contributor.authorvan Deurzen, Carolien H M
dc.contributor.authorvan Leeuwen, Flora E
dc.contributor.authorvan Ongeval, Chantal
dc.contributor.authorVan't Veer, Laura J
dc.contributor.authorWang, Qin
dc.contributor.authorWendt, Camilla
dc.contributor.authorWestenend, Pieter J
dc.contributor.authorHooning, Maartje J
dc.contributor.authorSchmidt, Marjanka K
dc.date.accessioned2020-01-28T02:37:29Z
dc.date.available2020-01-28T02:37:29Z
dc.date.issued2019-12-17
dc.identifier.issn1465-5411
dc.identifier.other31847907
dc.identifier.otherPMC6918633
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/301369
dc.description.abstractBACKGROUND:Breast cancer survivors are at risk for contralateral breast cancer (CBC), with the consequent burden of further treatment and potentially less favorable prognosis. We aimed to develop and validate a CBC risk prediction model and evaluate its applicability for clinical decision-making. METHODS:We included data of 132,756 invasive non-metastatic breast cancer patients from 20 studies with 4682 CBC events and a median follow-up of 8.8 years. We developed a multivariable Fine and Gray prediction model (PredictCBC-1A) including patient, primary tumor, and treatment characteristics and BRCA1/2 germline mutation status, accounting for the competing risks of death and distant metastasis. We also developed a model without BRCA1/2 mutation status (PredictCBC-1B) since this information was available for only 6% of patients and is routinely unavailable in the general breast cancer population. Prediction performance was evaluated using calibration and discrimination, calculated by a time-dependent area under the curve (AUC) at 5 and 10 years after diagnosis of primary breast cancer, and an internal-external cross-validation procedure. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. RESULTS:In the multivariable model, BRCA1/2 germline mutation status, family history, and systemic adjuvant treatment showed the strongest associations with CBC risk. The AUC of PredictCBC-1A was 0.63 (95% prediction interval (PI) at 5 years, 0.52-0.74; at 10 years, 0.53-0.72). Calibration-in-the-large was -0.13 (95% PI: -1.62-1.37), and the calibration slope was 0.90 (95% PI: 0.73-1.08). The AUC of Predict-1B at 10 years was 0.59 (95% PI: 0.52-0.66); calibration was slightly lower. Decision curve analysis for preventive contralateral mastectomy showed potential clinical utility of PredictCBC-1A between thresholds of 4-10% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers. CONCLUSIONS:We developed a reasonably calibrated model to predict the risk of CBC in women of European-descent; however, prediction accuracy was moderate. Our model shows potential for improved risk counseling, but decision-making regarding contralateral preventive mastectomy, especially in the general breast cancer population where limited information of the mutation status in BRCA1/2 is available, remains challenging.
dc.languageeng
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1465-542X
dc.sourcenlmid: 100927353
dc.subjectClinical Decision-making
dc.subjectContralateral Breast Cancer
dc.subjectRisk Prediction Model
dc.subjectBrca Mutation Carriers
dc.titlePrediction and clinical utility of a contralateral breast cancer risk model.
dc.typeArticle
dc.date.updated2020-01-28T02:37:29Z
dc.identifier.doi10.17863/CAM.48450
rioxxterms.versionofrecord10.1186/s13058-019-1221-1
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidBlomqvist, Carl [0000-0003-3041-1938]
pubs.funder-project-idCancer Research UK (C1275/C22524, C1275/A19187, C1275/A15956, C1287/A10118, C490/A16561, C1275/A11699, C490/A10124, C1287/A16563)
pubs.funder-project-idNCI NIH HHS (UM1 CA164920)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International