@article{a32311b0406f4a4083a59de84f57dad8,
title = "Population-based estimates of breast cancer risk for carriers of pathogenic variants identified by gene-panel testing",
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.",
author = "Southey, {Melissa C.} and Dowty, {James G.} and Moeen Riaz and Steen, {Jason A.} and Renault, {Anne Laure} and Katherine Tucker and Judy Kirk and Paul James and Ingrid Winship and Nicholas Pachter and Nicola Poplawski and Scott Grist and Park, {Daniel J.} and Pope, {Bernard J.} and Khalid Mahmood and Fleur Hammet and Maryam Mahmoodi and Helen Tsimiklis and Derrick Theys and Amanda Rewse and Amanda Willis and April Morrow and Catherine Speechly and Rebecca Harris and Robert Sebra and Eric Schadt and Paul Lacaze and McNeil, {John J.} and Giles, {Graham G.} and Milne, {Roger L.} and Hopper, {John L.} and T{\'u} Nguyen-Dumont",
note = "Funding Information: We thank all the participants in this study, the entire team of the Australian Breast Cancer Family Study/Registry (BCFR-AU) and past and current investigators. This work was supported by the U.S. National Institute of Health (grant number RO1CA159868). The ABCFS was supported in Australia by the National Health and Medical Research Council, the New South Wales Cancer Council, the Victorian Health Promotion Foundation, the Victorian Breast Cancer Research Consortium, Cancer Australia, and the National Breast Cancer Foundation. The six sites of the Breast Cancer Family Registry (BCFR) were supported by grant UM1 CA164920 from the U.S. National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the BCFR. T.N-.D is a National Breast Cancer Foundation (Australia) Career Development Fellow (ECF-17–001), B.J.P. is the recipient of a Victorian Health and Medical Research Fellowship and MCS is a National Health and Medical Research Council (NMHRC, Australia) Senior Research Fellow (APP1155163). This work was supported by an NHMRC Program grant (APP1074383), The National Breast Cancer Foundation (BRA-STRAP; NT-15-016), NHMRC European Union Collaborative Research Grant (APP1101400) and Monash University, Melbourne, Australia. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
day = "9",
doi = "10.1038/s41523-021-00360-3",
language = "English",
volume = "7",
journal = "npj Breast Cancer",
issn = "2374-4677",
publisher = "Nature Publishing Group",
number = "1",
}
