TY - JOUR
T1 - Polygenic breast cancer risk for women veterans in the million veteran program
AU - Minnier, Jessica
AU - Rajeevan, Nallakkandi
AU - Gao, Lina
AU - Park, Byung
AU - Pyarajan, Saiju
AU - Spellman, Paul
AU - Haskell, Sally G.
AU - Brandt, Cynthia A.
AU - Luoh, Shiuh Wen
N1 - Publisher Copyright:
© 2021 American Society of Clinical Oncology. All rights reserved.
PY - 2021
Y1 - 2021
N2 - PURPOSE Accurate breast cancer (BC) risk assessment allows personalized screening and prevention. Prospective validation of prediction models is required before clinical application. Here, we evaluate clinical- and genetic-based BC prediction models in a prospective cohort of women from the Million Veteran Program. MATERIALS AND METHODS Clinical BC risk prediction models were validated in combination with a genetic polygenic risk score of 313 (PRS313) single-nucleotide polymorphisms in genetic females without prior BC diagnosis (n = 35,130, mean age 49 years) with 30% non-Hispanic African ancestry (AA). Clinical risk models tested were Breast and Prostate Cancer Cohort Consortium, literature review, and Breast Cancer Risk Assessment Tool, and implemented with or without PRS313. Prediction accuracy and association with incident breast cancer was evaluated with area under the receiver operating characteristic curve (AUC), hazard ratios, and proportion with high absolute lifetime risk. RESULTS Three hundred thirty-eight participants developed incident breast cancers with a median follow-up of 3.9 years (2.5 cases/1,000 person-years), with 196 incident cases in women of European ancestry and 112 incident cases in AA women. Individualized Coherent Absolute Risk Estimator-literature review in combination with PRS313 had an AUC of 0.708 (95% CI, 0.659 to 0.758) in women with European or non-African ancestries and 0.625 (0.539 to 0.711) in AA women. Breast Cancer Risk Assessment Tool with PRS313 had an AUC of 0.695 (0.62 to 0.729) in European or non-AA and 0.675 (0.626 to 0.723) in AA women. Incorporation of PRS313 with clinical models improved prediction in European but not in AA women. Models estimated up to 9% of European and 18% of AA women with absolute lifetime risk . 20%. CONCLUSION Clinical and genetic BC risk models predict incident BC in a large prospective multiracial cohort; however, more work is needed to improve genetic risk estimation in AA women.
AB - PURPOSE Accurate breast cancer (BC) risk assessment allows personalized screening and prevention. Prospective validation of prediction models is required before clinical application. Here, we evaluate clinical- and genetic-based BC prediction models in a prospective cohort of women from the Million Veteran Program. MATERIALS AND METHODS Clinical BC risk prediction models were validated in combination with a genetic polygenic risk score of 313 (PRS313) single-nucleotide polymorphisms in genetic females without prior BC diagnosis (n = 35,130, mean age 49 years) with 30% non-Hispanic African ancestry (AA). Clinical risk models tested were Breast and Prostate Cancer Cohort Consortium, literature review, and Breast Cancer Risk Assessment Tool, and implemented with or without PRS313. Prediction accuracy and association with incident breast cancer was evaluated with area under the receiver operating characteristic curve (AUC), hazard ratios, and proportion with high absolute lifetime risk. RESULTS Three hundred thirty-eight participants developed incident breast cancers with a median follow-up of 3.9 years (2.5 cases/1,000 person-years), with 196 incident cases in women of European ancestry and 112 incident cases in AA women. Individualized Coherent Absolute Risk Estimator-literature review in combination with PRS313 had an AUC of 0.708 (95% CI, 0.659 to 0.758) in women with European or non-African ancestries and 0.625 (0.539 to 0.711) in AA women. Breast Cancer Risk Assessment Tool with PRS313 had an AUC of 0.695 (0.62 to 0.729) in European or non-AA and 0.675 (0.626 to 0.723) in AA women. Incorporation of PRS313 with clinical models improved prediction in European but not in AA women. Models estimated up to 9% of European and 18% of AA women with absolute lifetime risk . 20%. CONCLUSION Clinical and genetic BC risk models predict incident BC in a large prospective multiracial cohort; however, more work is needed to improve genetic risk estimation in AA women.
UR - http://www.scopus.com/inward/record.url?scp=85116481166&partnerID=8YFLogxK
U2 - 10.1200/PO.20.00541
DO - 10.1200/PO.20.00541
M3 - Article
AN - SCOPUS:85116481166
SN - 2473-4284
VL - 5
SP - 1178
EP - 1191
JO - JCO Precision Oncology
JF - JCO Precision Oncology
ER -