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

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.
Competing Interests: Belinda CreightonEmployment: Cancer Specialists 1/84 Bridge Rd, Richmond VIC 3121 AustraliaConsulting or Advisory Role: Bristol Myers Squibb, Eisai Dinuka AriyaratneResearch Funding: AstraZeneca Elizabeth ChristieHonoraria: AstraZeneca Sian FeredayConsulting or Advisory Role: Geneseq Biosciences Pty LtdResearch Funding: AstraZeneca (Inst), AstraZeneca (Inst) Nadia TraficanteResearch Funding: AstraZeneca (Inst) Bryony ThompsonConsulting or Advisory Role: Genetic Technologies Kenneth DoigStock and Other Ownership Interests: CSL Limited Christopher LoveEmployment: Geneseq Biosciences Yeh Chen LeeConsulting or Advisory Role: GlaxoSmithKlineResearch Funding: AstraZeneca (Inst)Travel, Accommodations, Expenses: AstraZeneca Rachel WilliamsHonoraria: AstraZeneca Andrew N. StephensConsulting or Advisory Role: Invion Pty Ltd (Inst)Research Funding: Invion Pty Ltd (Inst) Adeline TanEmployment: Sonic HealthcareStock and Other Ownership Interests: Sonic Healthcare Stephen B. FoxConsulting or Advisory Role: Novartis (Inst), BMS (Inst), AstraZeneca (Inst), MSD (Inst), Pfizer (Inst), Roche (Inst)Research Funding: AstraZeneca (Inst), Amgen (Inst), Roche (Inst), BMS (Inst)Expert Testimony: AstraZeneca (Inst), MSD (Inst)Travel, Accommodations, Expenses: Ventana Medical Systems, AstraZeneca, MSD Mary-Anne YoungUncompensated Relationships: Illumina (Inst) Jane HillOther Relationship: Medicines Australia Paul A. CohenEmployment: St John of God HealthcareStock and Other Ownership Interests: Clinic IQHonoraria: AstraZenecaConsulting or Advisory Role: Clinic IQResearch Funding: ANZGOG, St John of God Foundation Penelope M. WebbResearch Funding: AstraZeneca (Inst) Michael FriedlanderHonoraria: AstraZeneca, MSD, Lilly, Takeda, Novartis, GlaxoSmithKlineConsulting or Advisory Role: AstraZeneca, MSD, AbbVie, Lilly, Takeda, Novartis, GlaxoSmithKlineSpeakers' Bureau: AstraZeneca, ACT GenomicsResearch Funding: BeiGene (Inst), AstraZeneca (Inst), Novartis (Inst)Travel, Accommodations, Expenses: AstraZeneca David BowtellHonoraria: AstraZenecaConsulting or Advisory Role: Exo TherapeuticsResearch Funding: Roche/Genentech, AstraZeneca, BeiGenePatents, Royalties, Other Intellectual Property: AstraZeneca Genentech Roche Kathryn AlsopResearch Funding: AstraZeneca (Inst)No other potential conflicts of interest were reported.