Women's Health and Oncology

Validating the Effectiveness of Cascade Genetic Testing and Cancer Surveillance

    Genetic testing for hereditary cancer syndromes can identify individuals carrying a pathogenic variant that increases risk for diseases such as breast and ovarian cancer before they develop, thus maximizing disease prevention and early detection. Cascade testing refers to the process of starting with the proband (or the first person in the family found to have the genetic variant) and extending genetic testing to the proband's at‐risk relatives. Those relatives who are discovered to carry the familial pathogenic variant can greatly benefit from intensive surveillance and risk‐reducing surgery. For example, for women with BRCA1/2 pathogenic variants, risk‐reducing bilateral salpingo‐oophorectomy and bilateral mastectomy are associated with a reduced risk of breast cancer, and salpingo‐oophorectomy is associated with a decreased risk of ovarian cancer and a dramatically lower mortality rate.

    image of Dr. Eloise Chapman-Davis

    Dr. Eloise Chapman-Davis

    image of Dr. Melissa Frey

    Dr. Melissa Frey

    The Office of Public Health Genomics of the Centers for Disease Control and Prevention has selected cascade genetic testing as a tier one genomic application for hereditary breast and ovarian cancer as well as for Lynch syndrome. And yet, the literature suggests that only about a third of at‐risk relatives follow through with the suggested genetic testing. In 2020, Eloise Chapman-Davis, MD, Director of Gynecologic Oncology, and Melissa K. Frey, MD, a gynecologist oncologist, in the Department of Obstetrics and Gynecology at NewYork-Presbyterian/Weill Cornell Medical Center, led a pilot study to evaluate the feasibility of clinician-facilitated cancer cascade testing by directly contacting the relative through telephone genetic counseling and by mailing saliva kit testing to their homes. This study, published in the 2020 issue of the Journal of Clinical Oncology, demonstrated successful cancer genetic testing for 58 percent of the identified relatives and for 70 percent of relatives reached by the research team significantly better than the current standard.

    While this increased use of genetic testing is encouraging, it is only clinically significant if the relatives act following the receipt of positive genetic testing results. With this in mind, Dr. Frey and Dr. Chapman-Davis conducted a two-year follow-up investigation to measure the long‐term utilization of targeted cancer prevention and quality of life among the at‐risk relatives offered cascade genetic testing in the first study.

    In the current study, the researchers re-contacted the relatives that had enrolled in the initial pilot study and were found on genetic testing to carry the familial cancer-associated pathogenic variant. The relatives were asked whether or not their genetic testing results had prompted completion of the cancer screening interventions or surgeries that were recommended on the basis of the National Comprehensive Cancer Network (NCCN) guidelines.

    Our long‐term follow‐up study demonstrates that clinician‐facilitated cascade testing can result in the successful completion of genetic testing and utilization of genetically targeted primary disease prevention through screening and risk‐reducing surgery.

    — Dr. Eloise Chapman-Davis, Dr. Melissa Frey, and study authors

    Ninety-five at-risk relatives were enrolled in the initial pilot study, and 72 (76 percent) participated in the two-year follow-up investigation. Of the 95 relatives, 57 (79 percent) had completed genetic testing. The results of the follow-up study, which were published in the October 27, 2022, issue of Cancer, showed:

    • 25 of the 57 relatives (44 percent) harbored an inherited pathogenic variant
    • Guideline-based cancer surveillance was recommended to 18 relatives who were informed that their affected gene, age, biologic sex, and personal medical history rendered them candidates for cancer surveillance based on NCCN guidelines
    • 13 of these 18 relatives (72 percent) completed at least one recommended screening
    • 6 relatives (33 percent) completed all recommended screenings
    • Risk-reducing surgery was recommended to 10 relatives, with 4 (40 percent) completing a total of 8 procedures, including bilateral salpingo‐oophorectomy (4), hysterectomy (3), and mastectomy (1)
    • Quality-of-life surveys demonstrated low levels of anxiety, depression, distress, and uncertainty

    Dr. Chapman-Davis and Dr. Frey and their research colleagues demonstrated that cascade testing offers the ability to extend genetic testing and disease prevention to disease‐free, at‐risk relatives and thus strengthen the potential benefits of cancer genetics. “As the true power of genetic testing relies on the translation of a positive testing result into cancer prevention and early detection, our results suggest that genetic navigation programs might consider focusing on both facilitating cascade genetic testing and encouraging affected individuals to engage with the medical system,” wrote the authors.

    Since the inception of genetic sequencing technology, there has been discussion that testing could bring about psychological distress. However, the Weill Cornell Medicine researchers assessed the long‐term quality of life and the psychosocial effects of clinician‐facilitated cascade testing on the study relatives and confirmed low levels of anxiety and depression and high levels of satisfaction with the experience.

      Read More

      What happens in the long term: Uptake of cancer surveillance and prevention strategies among at-risk relatives with pathogenic variants detected via cascade testing. Frey MK, Ahsan MD, Badiner N, Lin J, Narayan P, Nitecki R, Rauh-Hain JA, Moss H, Fowlkes RK, Thomas C, Bergeron H, Christos P, Levi SR, Blank SV, Holcomb K, Cantillo E, Sharaf RN, Lipkin S, Offit K, Chapman-Davis E. Cancer. 2022 Dec 15;128(24):4241-4250.

      Prospective Feasibility Trial of a Novel Strategy of Facilitated Cascade Genetic Testing Using Telephone Counseling. Frey MK, Kahn RM, Chapman‐Davis E, et al. Journal of Clinical Oncology. 2020;38(13):1389‐1397.

      For more information

      Dr. Eloise Chapman-Davis
      Dr. Eloise Chapman-Davis
      [email protected]
      Dr. Melissa Frey
      Dr. Melissa Frey
      [email protected]