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Cascade testing in an ovarian cancer traceback genetic testing program: The GRACE study experience.

Jamilyn M Zepp1, Heather S Feigelson2, Yolanda K Prado1

  • 1Department of Translational and Applied Genomics, Kaiser Permanente Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon, USA.

Journal of Genetic Counseling
|November 5, 2025
PubMed
Summary

Genetic traceback testing for ovarian cancer (OC) survivors and relatives identified new cancer risk variants. This approach, offered years after initial diagnosis, proved feasible and effective in U.S. healthcare settings for hereditary cancer risk assessment.

Keywords:
cascade testingfamily historygenetic testingovarian cancertraceback

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Area of Science:

  • Genetics
  • Oncology
  • Public Health

Background:

  • Approximately 20% of ovarian cancer (OC) patients harbor inherited cancer risk gene variants.
  • Genetic testing is recommended at OC diagnosis, but many patients and their relatives miss this opportunity.
  • Hereditary cancer risk information and genetic testing can benefit individuals at any time.

Purpose of the Study:

  • To evaluate the feasibility and effectiveness of a traceback genetic testing program for ovarian cancer survivors and their at-risk relatives (ARR).
  • To assess cascade testing uptake and outcomes in a U.S. healthcare setting.
  • To identify individuals with pathogenic or likely pathogenic (P/LP) variants in cancer risk genes.

Main Methods:

  • The Genetic Risk Assessment in Ovarian CancEr (GRACE) study offered panel-based genetic testing to OC survivors untested at diagnosis and relatives of deceased OC patients.
  • Positive results triggered cascade testing offers to ARR, with support for communication and direct contact options.
  • Testing occurred 10-12 years post-OC diagnosis.

Main Results:

  • Traceback testing identified 20 P/LP variants, making 93 ARR eligible for cascade testing.
  • Cascade testing uptake was 38%, identifying 11 individuals with OC-risk variants and 3 incidental findings.
  • Women showed higher cascade testing completion rates (45%) than men (30%).

Conclusions:

  • Traceback genetic testing programs are feasible and effective in U.S. healthcare systems for identifying hereditary cancer risks.
  • Cascade testing facilitates the identification of at-risk relatives, even years after the initial cancer diagnosis.
  • This strategy enhances cancer risk assessment and potential early intervention for families affected by ovarian cancer.