Submitter Withdrawn Oral - Post Notification Clinical Oncology Society of Australia Annual Scientific Meeting 2023

Universal germline mutation testing is better at the detection of breast cancer genetic mutations, clinically impactful and highly acceptable to clinicians and patients (#97)

Dilanka L De Silva 1 2 , Lesley Stafford 2 3 , Anita Skandarajah 2 3 , Michelle Sinclair 4 , Lisa Devereux 2 5 , Kirsten Hogg 6 , Maira Kentwell 1 , Allan Park 3 , Luxi Lal 2 7 , Magnus Zethoven 5 , Madawa Jayawardena 2 5 , Fiona Chan 8 , Paul James 1 2 3 5 , Bruce Mann 2 3 4 , Ian Campbell 2 5 , Geoffrey Lindeman 1 2 5 7
  1. Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne , VIC, Australia
  2. The University of Melbourne, Melbourne, VIC, Australia
  3. Royal Melbourne Hospital, Melbourne , VIC, Australia
  4. Royal Women's Hospital, Melbourne, VIC, Australia
  5. Oncology, Peter MacCallum Cancer Centre, Melbourne , VIC, Australia
  6. Murdoch Children’s Research Institute, Melbourne , VIC, Australia
  7. Walter and Eliza Hall Institute of Medical Research, Melbourne , VIC, Australia
  8. The Royal Children's Hospital Melbourne, Melbourne , VIC, Australia

Background: For newly diagnosed breast cancer (BC) patients, identification of pathogenic germline mutations in hereditary breast cancer (HBC) genes can inform clinical management and risk mitigation strategies and identify patients who would benefit from targeted therapy and clinical trials. Offering germline testing based on current guidelines fails to identify all patients with germline HBC gene mutations, potentially with adverse consequences for patients and their families. 

Methods: This is the largest Australian multi-centre prospective study exploring the prevalence of hereditary BC genes. 650 newly diagnosed consecutive patients with non-metastatic breast cancer or high-grade DCIS were recruited from May 2020 to March 2023 in two phases. Phase 1 (n=157) offered a combination of germline and somatic sequencing, with Phase 2 offering germline testing only. The objectives were to assess the additional actionable HBC gene mutations identified by universal testing compared to algorithmic-based (MANCHESTER and BOADICEA scores) and NCCN guidelines, the prevalence of germline mutations and the clinical impact. Phase 1 participants completed surveys of their perceptions of universal testing, psychological distress, and cancer-specific worry pre-and post-testing.

Results: Actionable germline mutations were identified in 7.7%. Genes included BRCA1 (n=10), BRCA2 (n=12), PALB2 (n=7), CHEK2 (n=10), ATM (n=4), PMS2 (n=2), MSH6 (n=1), RAD51C (n=2), and BARD1 (n=3). NCCN guidelines identified 44/50 (88%), and BOADICEA and MANCHESTER scores identified 22/50 (44%) cases. Clinical management changed in 40/50 (80%) cases. Among 105 participants, cancer-specific distress, anxiety, stress, and depression did not increase. 90/103 participants agreed that genetic testing should be routine, and 100/104 reported their decision to undergo testing as correct. All (n=25) BC clinicians reported that genetic test results were helpful.

Conclusion: Current Australian testing guidelines missed more than 50% of HBC gene mutations. The discovery of mutations led to changed management in most cases, and universal testing is highly acceptable to clinicians and patients.