TRACEBACK: Testing of Historical Tubo-Ovarian Cancer Patients for Hereditary Risk Genes as a Cancer Prevention Strategy in Family Members

• DOI: 10.1200/jco.21.02108
• Publication Date: 2022-03-09T20:59:42Z
• Authors: Rachel Delahunty; Linh Nguyen; Stuart Craig; Belinda Creighton; Dinuka Ariyaratne; Dale W. Garsed; Elizabeth Christie; Sian Fereday; Lesley Andrews; Alexandra Lewis; Sharne Limb; Ahwan Pandey; Joy Hendley; Nadia Traficante; Natalia Carvajal; Amanda B. Spurdle; Bryony Thompson; Michael T. Parsons; Victoria Beshay; Mila Volcheck; Timothy Semple; Richard Lupat; Kenneth Doig; Jiaan Yu; Xiao Qing Chen; Anna Marsh; Christopher Love; Sanela Bilic; Maria Beilin; Cassandra B. Nichols; Christina Greer; Yeh Chen Lee; Susan Gerty; Lynette Gill; Emma Newton; Julie Howard; Rachel Williams; Christie Norris; Andrew N. Stephens; Erin Tutty; Courtney Smyth; Shona O'Connell; Thomas Jobling; Colin J.R. Stewart; Adeline Tan; Stephen B. Fox; Nicholas Pachter; Jason Li; Jason Ellul; Gisela Mir Arnau; Mary-Anne Young; Louisa Gordon; Laura Forrest; Marion Harris; Karen Livingstone; Jane Hill; Georgia Chenevix-...; Paul A. Cohen; Penelope M. Webb; Michael Friedlander; Paul James; David Bowtell; Kathryn Alsop
• Keywords: Male; Ovarian Neoplasms; 0301 basic medicine; Australia; 610; Breast Neoplasms; Pilot Projects; ORIGINAL REPORTS; Carcinoma, Ovarian Epithelial; 03 medical and health sciences; Humans; Family; Female; Genetic Predisposition to Disease; Genetic Testing; Retrospective Studies

PURPOSE Tubo-ovarian cancer (TOC) is a sentinel cancer for BRCA1 and BRCA2 pathogenic variants (PVs). Identification of a PV in the first member of a family at increased genetic risk (the proband) provides opportunities for cancer prevention in other at-risk family members. Although Australian testing rates are now high, PVs in patients with TOC whose diagnosis predated revised testing guidelines might have been missed. We assessed the feasibility of detecting PVs in this population to enable genetic risk reduction in relatives. PATIENTS AND METHODS In this pilot study, deceased probands were ascertained from research cohort studies, identification by a relative, and gynecologic oncology clinics. DNA was extracted from archival tissue or stored blood for panel sequencing of 10 risk-associated genes. Testing of deceased probands ascertained through clinic records was performed with a consent waiver. RESULTS We identified 85 PVs in 84 of 787 (11%) probands. Familial contacts of 39 of 60 (65%) deceased probands with an identified recipient (60 of 84; 71%) have received a written notification of results, with follow-up verbal contact made in 85% (33 of 39). A minority of families (n = 4) were already aware of the PV. For many (29 of 33; 88%), the genetic result provided new information and referral to a genetic service was accepted in most cases (66%; 19 of 29). Those who declined referral (4 of 29) were all male next of kin whose family member had died more than 10 years before. CONCLUSION We overcame ethical and logistic challenges to demonstrate that retrospective genetic testing to identify PVs in previously untested deceased probands with TOC is feasible. Understanding reasons for a family member's decision to accept or decline a referral will be important for guiding future TRACEBACK projects.