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dc.contributor.authorLacaze, P
dc.contributor.authorBakshi, A
dc.contributor.authorRiaz, M
dc.contributor.authorOrchard, SG
dc.contributor.authorTiller, J
dc.contributor.authorNeumann, JT
dc.contributor.authorCarr, PR
dc.contributor.authorJoshi, AD
dc.contributor.authorCao, Y
dc.contributor.authorWarner, ET
dc.contributor.authorManning, A
dc.contributor.authorNguyen-Dumont, T
dc.contributor.authorSouthey, MC
dc.contributor.authorMilne, RL
dc.contributor.authorFord, L
dc.contributor.authorSebra, R
dc.contributor.authorSchadt, E
dc.contributor.authorGately, L
dc.contributor.authorGibbs, P
dc.contributor.authorThompson, BA
dc.contributor.authorMacrae, FA
dc.contributor.authorJames, P
dc.contributor.authorWinship, I
dc.contributor.authorMcLean, C
dc.contributor.authorZalcberg, JR
dc.contributor.authorWoods, RL
dc.contributor.authorChan, AT
dc.contributor.authorMurray, AM
dc.contributor.authorMcNeil, JJ
dc.date.accessioned2021-10-12T00:21:16Z
dc.date.available2021-10-12T00:21:16Z
dc.date.issued2021-07-01
dc.identifierpii: cancers13143533
dc.identifier.citationLacaze, P., Bakshi, A., Riaz, M., Orchard, S. G., Tiller, J., Neumann, J. T., Carr, P. R., Joshi, A. D., Cao, Y., Warner, E. T., Manning, A., Nguyen-Dumont, T., Southey, M. C., Milne, R. L., Ford, L., Sebra, R., Schadt, E., Gately, L., Gibbs, P. ,... McNeil, J. J. (2021). Genomic Risk Prediction for Breast Cancer in Older Women. CANCERS, 13 (14), https://doi.org/10.3390/cancers13143533.
dc.identifier.issn2072-6694
dc.identifier.urihttp://hdl.handle.net/11343/287416
dc.description.abstractGenomic risk prediction models for breast cancer (BC) have been predominantly developed with data from women aged 40-69 years. Prospective studies of older women aged ≥70 years have been limited. We assessed the effect of a 313-variant polygenic risk score (PRS) for BC in 6339 older women aged ≥70 years (mean age 75 years) enrolled into the ASPREE trial, a randomized double-blind placebo-controlled clinical trial investigating the effect of daily 100 mg aspirin on disability-free survival. We evaluated incident BC diagnoses over a median follow-up time of 4.7 years. A multivariable Cox regression model including conventional BC risk factors was applied to prospective data, and re-evaluated after adding the PRS. We also assessed the association of rare pathogenic variants (PVs) in BC susceptibility genes (BRCA1/BRCA2/PALB2/CHEK2/ATM). The PRS, as a continuous variable, was an independent predictor of incident BC (hazard ratio (HR) per standard deviation (SD) = 1.4, 95% confidence interval (CI) 1.3-1.6) and hormone receptor (ER/PR)-positive disease (HR = 1.5 (CI 1.2-1.9)). Women in the top quintile of the PRS distribution had over two-fold higher risk of BC than women in the lowest quintile (HR = 2.2 (CI 1.2-3.9)). The concordance index of the model without the PRS was 0.62 (95% CI 0.56-0.68), which improved after addition of the PRS to 0.65 (95% CI 0.59-0.71). Among 41 (0.6%) carriers of PVs in BC susceptibility genes, we observed no incident BC diagnoses. Our study demonstrates that a PRS predicts incident BC risk in women aged 70 years and older, suggesting potential clinical utility extends to this older age group.
dc.languageEnglish
dc.publisherMDPI
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleGenomic Risk Prediction for Breast Cancer in Older Women
dc.typeJournal Article
dc.identifier.doi10.3390/cancers13143533
melbourne.affiliation.departmentMelbourne School of Population and Global Health
melbourne.affiliation.departmentClinical Pathology
melbourne.affiliation.departmentMedicine (RMH)
melbourne.affiliation.departmentSurgery (RMH)
melbourne.affiliation.departmentMedicine (St Vincent's)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleCancers
melbourne.source.volume13
melbourne.source.issue14
dc.rights.licenseCC BY
melbourne.elementsid1559264
melbourne.contributor.authorNguyen, Binh Thieu Tu
melbourne.contributor.authorThompson, Bryony
melbourne.contributor.authorMacrae, Finlay
melbourne.contributor.authorGibbs, Peter
melbourne.contributor.authorMilne, Roger
melbourne.contributor.authorWinship, Ingrid
melbourne.contributor.authorZalcberg, John
dc.identifier.eissn2072-6694
melbourne.accessrightsOpen Access


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