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Southey MC, Dowty JG, Riaz M, et al. Population-based estimates of breast cancer risk for carriers of pathogenic variants identified by gene-panel testing. NPJ Breast Cancer. 2021;7(1):153doi: 10.1038/s41523-021-00360-3.
Southey, M. C., Dowty, J. G., Riaz, M., Steen, J. A., Renault, A. L., Tucker, K., Kirk, J., James, P., Winship, I., Pachter, N., Poplawski, N., Grist, S., Park, D. J., Pope, B. J., Mahmood, K., Hammet, F., Mahmoodi, M., Tsimiklis, H., Theys, D., Rewse, A., Willis, A., Morrow, A., Speechly, C., Harris, R., Sebra, R., Schadt, E., Lacaze, P., McNeil, J. J., Giles, G. G., Milne, R. L., Hopper, J. L., & Nguyen-Dumont, T. (2021). Population-based estimates of breast cancer risk for carriers of pathogenic variants identified by gene-panel testing. NPJ breast cancer, 7(1), 153. https://doi.org/10.1038/s41523-021-00360-3
Southey, Melissa C, et al. "Population-based estimates of breast cancer risk for carriers of pathogenic variants identified by gene-panel testing." NPJ breast cancer vol. 7,1 (2021): 153. doi: https://doi.org/10.1038/s41523-021-00360-3
Southey MC, Dowty JG, Riaz M, Steen JA, Renault AL, Tucker K, Kirk J, James P, Winship I, Pachter N, Poplawski N, Grist S, Park DJ, Pope BJ, Mahmood K, Hammet F, Mahmoodi M, Tsimiklis H, Theys D, Rewse A, Willis A, Morrow A, Speechly C, Harris R, Sebra R, Schadt E, Lacaze P, McNeil JJ, Giles GG, Milne RL, Hopper JL, Nguyen-Dumont T. Population-based estimates of breast cancer risk for carriers of pathogenic variants identified by gene-panel testing. NPJ Breast Cancer. 2021 Dec 09;7(1):153. doi: 10.1038/s41523-021-00360-3. PMID: 34887416.
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NPJ Breast Cancer. 2021 Dec 09;7(1):153. doi: 10.1038/s41523-021-00360-3.

Population-based estimates of breast cancer risk for carriers of pathogenic variants identified by gene-panel testing.

NPJ breast cancer

Melissa C Southey, James G Dowty, Moeen Riaz, Jason A Steen, Anne-Laure Renault, Katherine Tucker, Judy Kirk, Paul James, Ingrid Winship, Nicholas Pachter, Nicola Poplawski, Scott Grist, Daniel J Park, Bernard J Pope, Khalid Mahmood, Fleur Hammet, Maryam Mahmoodi, Helen Tsimiklis, Derrick Theys, Amanda Rewse, Amanda Willis, April Morrow, Catherine Speechly, Rebecca Harris, Robert Sebra, Eric Schadt, Paul Lacaze, John J McNeil, Graham G Giles, Roger L Milne, John L Hopper, Tú Nguyen-Dumont

Affiliations

  1. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia. [email protected].
  2. Department of Clinical Pathology, The University of Melbourne, Melbourne, Australia. [email protected].
  3. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia. [email protected].
  4. Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, Australia.
  5. Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
  6. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Australia.
  7. Hereditary Cancer Centre, Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Sydney, Australia.
  8. Familial Cancer Services, Westmead Hospital, Westmead, Australia.
  9. Peter MacCallum Cancer Centre, Melbourne, Australia.
  10. Royal Melbourne Hospital, Melbourne, Australia.
  11. Department of Medicine, The University of Melbourne, Melbourne, Australia.
  12. King Edward Memorial Hospital, Perth, Australia.
  13. Adult Genetics Unit, Royal Adelaide Hospital, Adelaide, Australia.
  14. School of Medicine, University of Adelaide, Adelaide, Australia.
  15. SA Pathology, Flinders Medical Centre, Adelaide, Australia.
  16. Melbourne Bioinformatics, The University of Melbourne, Melbourne, Australia.
  17. Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, Australia.
  18. Department of Clinical Pathology, The University of Melbourne, Melbourne, Australia.
  19. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  20. Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Australia.

PMID: 34887416 DOI: 10.1038/s41523-021-00360-3

Abstract

Population-based estimates of breast cancer risk for carriers of pathogenic variants identified by gene-panel testing are urgently required. Most prior research has been based on women selected for high-risk features and more data is needed to make inference about breast cancer risk for women unselected for family history, an important consideration of population screening. We tested 1464 women diagnosed with breast cancer and 862 age-matched controls participating in the Australian Breast Cancer Family Study (ABCFS), and 6549 healthy, older Australian women enroled in the ASPirin in Reducing Events in the Elderly (ASPREE) study for rare germline variants using a 24-gene-panel. Odds ratios (ORs) were estimated using unconditional logistic regression adjusted for age and other potential confounders. We identified pathogenic variants in 11.1% of the ABCFS cases, 3.7% of the ABCFS controls and 2.2% of the ASPREE (control) participants. The estimated breast cancer OR [95% confidence interval] was 5.3 [2.1-16.2] for BRCA1, 4.0 [1.9-9.1] for BRCA2, 3.4 [1.4-8.4] for ATM and 4.3 [1.0-17.0] for PALB2. Our findings provide a population-based perspective to gene-panel testing for breast cancer predisposition and opportunities to improve predictors for identifying women who carry pathogenic variants in breast cancer predisposition genes.

© 2021. The Author(s).

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