Projects per year
Abstract
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 dis-ability-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.
Original language | English |
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Article number | 3533 |
Number of pages | 12 |
Journal | Cancers |
Volume | 13 |
Issue number | 14 |
DOIs | |
Publication status | Published - Jul 2021 |
Keywords
- Breast cancer
- Genomics
- Germline
- Polygenic risk score
- Risk prediction
Projects
- 3 Finished
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Genetic protection against cardiovascular disease in the healthy elderly
1/01/20 → 31/12/23
Project: Research
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ASPREE Completion Project
McNeil, J., Nelson, M., Tonkin, A. & Woods, R.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/16 → 31/12/18
Project: Research
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A randomised double-blind placebo-controlled trial of aspirin in primary prevention of CVD events or dementia in the aged ID: 334047
McNeil, J., Beilin, L. J., Krum, H., Nelson, M., Reid, C. & Tonkin, A.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/05 → 31/12/09
Project: Research