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Genomic risk prediction for breast cancer in older women

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Genomic risk prediction for breast cancer in older women. / Lacaze, Paul; Bakshi, Andrew; Riaz, Moeen; Orchard, Suzanne G.; Tiller, Jane; Neumann, Johannes T.; Carr, Prudence R.; Joshi, Amit D.; Cao, Yin; Warner, Erica T.; Manning, Alisa; Nguyen-Dumont, T.; Southey, Melissa C.; Milne, Roger L.; Ford, Leslie; Sebra, Robert; Schadt, Eric; Gately, Lucy; Gibbs, Peter; Thompson, Bryony A.; Macrae, Finlay A.; James, Paul; Winship, Ingrid; McLean, Catriona; Zalcberg, John R.; Woods, Robyn L.; Chan, Andrew T.; Murray, Anne M.; McNeil, John J.

in: CANCERS, Jahrgang 13, Nr. 14, 3533, 14.07.2021.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Lacaze, P, Bakshi, A, Riaz, M, Orchard, SG, Tiller, J, Neumann, JT, Carr, PR, Joshi, AD, Cao, Y, Warner, ET, Manning, A, Nguyen-Dumont, T, Southey, MC, Milne, RL, Ford, L, Sebra, R, Schadt, E, Gately, L, Gibbs, P, Thompson, BA, Macrae, FA, James, P, Winship, I, McLean, C, Zalcberg, JR, Woods, RL, Chan, AT, Murray, AM & McNeil, JJ 2021, 'Genomic risk prediction for breast cancer in older women', CANCERS, Jg. 13, Nr. 14, 3533. https://doi.org/10.3390/cancers13143533

APA

Lacaze, 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), [3533]. https://doi.org/10.3390/cancers13143533

Vancouver

Lacaze P, Bakshi A, Riaz M, Orchard SG, Tiller J, Neumann JT et al. Genomic risk prediction for breast cancer in older women. CANCERS. 2021 Jul 14;13(14). 3533. https://doi.org/10.3390/cancers13143533

Bibtex

@article{28a9272ff2b14c59b2a8c2823098a950,
title = "Genomic risk prediction for breast cancer in older women",
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.",
keywords = "Breast cancer, Genomics, Germline, Polygenic risk score, Risk prediction",
author = "Paul Lacaze and Andrew Bakshi and Moeen Riaz and Orchard, {Suzanne G.} and Jane Tiller and Neumann, {Johannes T.} and Carr, {Prudence R.} and Joshi, {Amit D.} and Yin Cao and Warner, {Erica T.} and Alisa Manning and T. Nguyen-Dumont and Southey, {Melissa C.} and Milne, {Roger L.} and Leslie Ford and Robert Sebra and Eric Schadt and Lucy Gately and Peter Gibbs and Thompson, {Bryony A.} and Macrae, {Finlay A.} and Paul James and Ingrid Winship and Catriona McLean and Zalcberg, {John R.} and Woods, {Robyn L.} and Chan, {Andrew T.} and Murray, {Anne M.} and McNeil, {John J.}",
note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2021",
month = jul,
day = "14",
doi = "10.3390/cancers13143533",
language = "English",
volume = "13",
journal = "CANCERS",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "14",

}

RIS

TY - JOUR

T1 - Genomic risk prediction for breast cancer in older women

AU - Lacaze, Paul

AU - Bakshi, Andrew

AU - Riaz, Moeen

AU - Orchard, Suzanne G.

AU - Tiller, Jane

AU - Neumann, Johannes T.

AU - Carr, Prudence R.

AU - Joshi, Amit D.

AU - Cao, Yin

AU - Warner, Erica T.

AU - Manning, Alisa

AU - Nguyen-Dumont, T.

AU - Southey, Melissa C.

AU - Milne, Roger L.

AU - Ford, Leslie

AU - Sebra, Robert

AU - Schadt, Eric

AU - Gately, Lucy

AU - Gibbs, Peter

AU - Thompson, Bryony A.

AU - Macrae, Finlay A.

AU - James, Paul

AU - Winship, Ingrid

AU - McLean, Catriona

AU - Zalcberg, John R.

AU - Woods, Robyn L.

AU - Chan, Andrew T.

AU - Murray, Anne M.

AU - McNeil, John J.

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/7/14

Y1 - 2021/7/14

N2 - 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.

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 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.

KW - Breast cancer

KW - Genomics

KW - Germline

KW - Polygenic risk score

KW - Risk prediction

UR - http://www.scopus.com/inward/record.url?scp=85110001987&partnerID=8YFLogxK

U2 - 10.3390/cancers13143533

DO - 10.3390/cancers13143533

M3 - SCORING: Journal article

AN - SCOPUS:85110001987

VL - 13

JO - CANCERS

JF - CANCERS

SN - 2072-6694

IS - 14

M1 - 3533

ER -