Oral Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2023

Universal germline testing for women with newly diagnosed breast cancer in a multidisciplinary setting – impact and benefit (#88)

Dilanka L De Silva 1 2 , Lesley Stafford 2 3 , Anita Skandarajah 2 3 , Michelle Sinclair 4 , Lisa Devereux 2 5 , Kirsten Hogg 2 6 , Maira Kentwell 1 2 , Allan Park 3 , Luxi Lal 3 5 6 , Magnus Zethoven 5 , Madawa W Jayawardana 2 5 , Fiona Chan 4 , Phyllis N Butow 7 , Paul A James 1 2 3 5 , Bruce Mann 2 3 4 , Ian G Campbell 2 5 , Geoffrey J Lindeman 1 2 3 6
  1. Parkville Familial Cancer Centre, The Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia
  2. The University of Melbourne, Melbourne, VIC, Australia
  3. The Royal Melbourne Hospital, Parkville, VIC, Australia
  4. The Royal Women’s Hospital, Parkville, VIC, Australia
  5. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  6. The Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  7. Centre for Medical Psychology and Evidence-based Decision Making, The University of Sydney, Sydney, NSW, Australia

Background: For patients with newly diagnosed breast cancer, identification of germline pathogenic variants in hereditary breast/ovarian cancer (HBOC) genes can inform clinical management and identify a subset who might benefit from targeted therapy. Current guidelines for germline testing, however, fail to identify all patients with germline pathogenic variants. The MAGIC (Mutational Assessment of newly diagnosed breast cancer using Germline and tumour genomICs) study examined whether universal germline testing is feasible, clinically useful, and acceptable to patients and clinicians.

Methods: Patients (n=650) with newly diagnosed non-metastatic breast cancer or high-grade pre-invasive disease were prospectively recruited through the Parkville Breast Service between June 2020 - March 2023 in 2 phases. Phase 1 participants (n=157) underwent germline and tumour DNA sequencing and their perceptions of genetic testing, psychological distress and cancer-specific worry were surveyed before and after genetic testing. Phase 2 participants (n=493) underwent germline testing only. Only pathogenic variants (Class 4 and 5) were reported. The yield of pathogenic variants identified by universal testing was compared to patients selected using current guidelines (Manchester ≥15 and CanRisk ≥10% scores) as well as recently updated NCCN (v3.2023) guidelines. Clinical management of participants with a pathogenic variant was formally re-considered at the Breast Service multidisciplinary team meeting.

Results: Pathogenic variants were identified in 50/650 (7.7%) participants, including in BRCA1 (n=10), BRCA2 (n=12), PALB2 (n=7), CHEK2 (n=10), ATM (n=4), RAD51C (n=2), BARD1 (n=3), PMS2 (n=2) and MSH6 (n=1). Twenty-two of 50 carriers (44%) would have met current genetic testing guidelines, using CanRisk and/or Manchester scores, while 44/50 (88%) met updated NCCN testing criteria. Clinical management changed in 40/50 (80%) of participants carrying a pathogenic variant. Acceptance of routine genetic testing was high among patients (90/103, 87% agreed, 13/103 neutral); no decision regret or adverse impact on psychological distress or cancer-specific worry were reported. Clinicians reported genetic test results helped treatment decisions; none reported patient distress.

Conclusion: Universal genetic testing following the diagnosis of breast cancer detects clinically significant germline pathogenic variants that might otherwise be missed because of testing guidelines. Routine testing and reporting of pathogenic variants is feasible and acceptable for both patients and clinicians.

  1. De Silva et al. Med J Aust. 2023 218(8):368-373. doi: 10.5694/mja2.51906