IARC 60th Anniversary - 19-21 May 2026
Session : 19/05/26 - Posters
BRA-STRAP : Updating decades of breast cancer predisposition testing and returning genetic findings
SRINIVASA S. 7, ANDREWS L. 4,16, KIRK J. 7,17, TUCKER K. 4,16, MORROW A. 4,16, NGUYEN-DUMONT T. 1,3, WILLIS A. 16, SOUTHEY M. 1,2,3, SPEECHLY C. 4, YOUNG A. 5, HARRAKA P. 1, BURKE J. 1, O'REILLY R. 1, CHEN P. 1, WINSHIP I. 3,6, HARRIS R. 7, AUSTIN R. 8, NICHOLS C. 9, MURPHY C. 10, ALLI R. 8, TSIMIKLIS H. 1, STEEN J. 1, JACOBS C. 11,12, ROSS K. 13, POPLAWSKI N. 15, PACHETER N. 9, MAR FAN H. 8
1 Monash University, Melbourne, Australia; 2 Cancer Council Victoria, Melbourne, Australia; 3 University of Melbourne, Parkville, Australia; 4 Prince of Wales Hospital, Sydney, Australia; 5 University of Newcastle, Callaghan, Australia; 6 Royal Melbourne Hospital, Parkville, Australia; 7 Westmead Hospital, Westmead, Australia; 8 Royal Brisbane and Women's Hospital, Herston, Australia; 9 King Edward Memorial Hospital, Subiaco, Australia; 10 Canberra Hospital, Canberra, Australia; 11 University of Technology Sydney, Sydney, Australia; 12 University of Surrey, Guildford, United Kingdom; 13 Women’s and Children’s Hospital, North Adelaide, Australia; 14 Royal Adelaide Hospital, Adelaide, Australia; 15 University of New South Wales, Sydney, Australia; 16 University of Sydney, Camperdown, Australia; 17 Garvan Institute of Medical Research, Darlinghurst, Australia
BRA-STRAP : Updating decades of breast cancer predisposition testing and returning genetic findings
Background:
Brca Refined Analysis of Sequence Tests: Risk and Penetrance (BRA-STRAP) was funded in 2015 by the National Breast Cancer Foundation (Australia) to conduct a nationwide study of genetic risk factors for breast cancer at a time when gene panel testing was just starting to become routine in diagnostic laboratories. These tests posed considerable challenge to clinical genetic services as very little was known about the cancer risks associated with the observed genetic variation. BRA-STRAP brought together 30,000 Australian women of all ages across the cancer risk spectrum, affected and unaffected with breast cancer, and their families with a focus on genomic information related to 24 genes commonly included on panel tests for breast cancer predisposition to address this challenge.
BRA-STRAP built a collaboration that included i) large research cohorts of aging populations and of women above population risk (population cohort component), and ii) the clinical genetics community and women who had attended an Australian familial cancer centre for breast cancer predisposition (FCC component) over the last two and a half decades.
Objective:
To update decades of breast cancer predisposition testing and return genetic findings to participants.
Methods:
The FCC component (conducted under a waiver of consent), included 8338 women who had prior genetic testing for breast cancer predisposition in clinical genetic services in Australia since 1998, predominantly involving only BRCA1 and BRCA2 analysis. DNAs were centralised and underwent a 24 gene panel test. Clinically actionable results were returned by participating FCCs to the patient, or if they were deceased the next-of-kin (NOK). The perspectives of genetic health providers (GHPs) and the women/NOK involved in the study about the patient recontacting processes were assessed. Semi-structured interviews explored perspectives on notification, consent and ethical issues.
Results:
In total 521 (6.2%) women participating in the FCC component who had previously tested negative were found to carry a pathogenic or likely pathogenic (PLP) variant in a gene currently supported by Australian best practice guidelines (eviQ). There were a total of 529 PLP variants identified, 32 (6.1%) in BRCA1, 37 (7.0%) in BRCA2, 86 (16.3%) in PALB2, 95 (18.0%) in ATM, 154 (29.1%) in CHEK2, 21 (4.0%) in TP53, 2 (0.4%) in PTEN, 12 (2.3%) in RAD51D and 22 (4.2%) in RAD51C, 13 (2.5%) in BARD1, 28 (5.3%) in BRIP1, 2 (0.4%) in CDH1, 3 (0.6%) in MLH1, 5 (1.0%) in MSH2, 8 (1.5%) in MSH6, 5 (1.0%) in NF1, and 4 (0.8%) in PMS2.
Results from the population cohort component have contributed to population-based estimates of age-specific cumulative risk of breast cancer for carriers of PLP variants in BRCA1, BRCA2, PALB2, CHEK2 and ATM.
Recontact of participants, even without updated consent, was considered by GHPs and patients/NOK to have clear benefits with relatively minimal burdens.
Conclusions:
BRA-STRAP updated breast cancer predisposition testing and returned findings to participants representing women across the breast cancer risk spectrum providing clear benefits to breast cancer risk management for them and their families.