TY  - JOUR
AU  - Lacaze, P
AU  - Bakshi, A
AU  - Riaz, M
AU  - Orchard, SG
AU  - Tiller, J
AU  - Neumann, JT
AU  - Carr, PR
AU  - Joshi, AD
AU  - Cao, Y
AU  - Warner, ET
AU  - Manning, A
AU  - Nguyen-Dumont, T
AU  - Southey, MC
AU  - Milne, RL
AU  - Ford, L
AU  - Sebra, R
AU  - Schadt, E
AU  - Gately, L
AU  - Gibbs, P
AU  - Thompson, BA
AU  - Macrae, FA
AU  - James, P
AU  - Winship, I
AU  - McLean, C
AU  - Zalcberg, JR
AU  - Woods, RL
AU  - Chan, AT
AU  - Murray, AM
AU  - McNeil, JJ
Y2  - 2021/10/12
Y1  - 2021/07/01
SN  - 2072-6694
UR  - http://hdl.handle.net/11343/287416
AB  - Genomic 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.
LA  - English
PB  - MDPI
T1  - Genomic Risk Prediction for Breast Cancer in Older Women
DO  - 10.3390/cancers13143533
IS  - Cancers
VL  - 13
IS  - 14
L1  - /bitstream/handle/11343/287416/PMC8305131.pdf?sequence=1&isAllowed=y
ER  -