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Meta-Analysis
. 2022 Dec 10;40(35):4129-4143.
doi: 10.1200/JCO.22.00303. Epub 2022 Aug 12.

Cascade Testing for Hereditary Cancer Syndromes: Should We Move Toward Direct Relative Contact? A Systematic Review and Meta-Analysis

Melissa K Frey  1 , Muhammad Danyal Ahsan  1 , Hannah Bergeron  1 , Jenny Lin  1 , Xuan Li  1 , Rana K Fowlkes  1 , Priyanka Narayan  1 , Roni Nitecki  2 , Jose Alejandro Rauh-Hain  2 , Haley A Moss  3 , Becky Baltich Nelson  1 , Charlene Thomas  1 , Paul J Christos  1 , Jada G Hamilton  4 , Eloise Chapman-Davis  1 , Evelyn Cantillo  1 , Kevin Holcomb  1 , Allison W Kurian  5 , Steven Lipkin  1 , Kenneth Offit  4 , Ravi N Sharaf  1
Affiliations
Meta-Analysis

Cascade Testing for Hereditary Cancer Syndromes: Should We Move Toward Direct Relative Contact? A Systematic Review and Meta-Analysis

Melissa K Frey et al. J Clin Oncol. .

Abstract

Purpose: Evidence-based guidelines recommend cascade genetic counseling and testing for hereditary cancer syndromes, providing relatives the opportunity for early detection and prevention of cancer. The current standard is for patients to contact and encourage relatives (patient-mediated contact) to undergo counseling and testing. Direct relative contact by the medical team or testing laboratory has shown promise but is complicated by privacy laws and lack of infrastructure. We sought to compare outcomes associated with patient-mediated and direct relative contact for hereditary cancer cascade genetic counseling and testing in the first meta-analysis on this topic.

Materials and methods: We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No.: CRD42020134276). We searched key electronic databases to identify studies evaluating hereditary cancer cascade testing. Eligible trials were subjected to meta-analysis.

Results: Eighty-seven studies met inclusion criteria. Among relatives included in the meta-analysis, 48% (95% CI, 38 to 58) underwent cascade genetic counseling and 41% (95% CI, 34 to 48) cascade genetic testing. Compared with the patient-mediated approach, direct relative contact resulted in significantly higher uptake of genetic counseling for all relatives (63% [95% CI, 49 to 75] v 35% [95% CI, 24 to 48]) and genetic testing for first-degree relatives (62% [95% CI, 49 to 73] v 40% [95% CI, 32 to 48]). Methods of direct contact included telephone calls, letters, and e-mails; respective rates of genetic testing completion were 61% (95% CI, 51 to 70), 48% (95% CI, 37 to 59), and 48% (95% CI, 45 to 50).

Conclusion: Most relatives at risk for hereditary cancer do not undergo cascade genetic counseling and testing, forgoing potentially life-saving medical interventions. Compared with patient-mediated contact, direct relative contact increased rates of cascade genetic counseling and testing, arguing for a shift in the care delivery paradigm, to be confirmed by randomized controlled trials.

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Conflict of interest statement

Kenneth Offit

Patents, Royalties, Other Intellectual Property: Patent pending on therapeutic applications of targeting ERCC3 mutations in cancer. Diagnosis & treatment of ercc3-mutant cancer US20210137850A1

Other Relationship: AnaNeo Therapeutics, Inc

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
PRISMA flow diagram. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
FIG 2.
FIG 2.
Cascade genetic counseling: pooled proportions with patient-mediated contact (A) and direct relative contact (B).
FIG 3.
FIG 3.
Cascade genetic testing: pooled proportions with patient-mediated contact (A) and direct relative contact (B).
FIG 4.
FIG 4.
Cascade genetic testing of first-degree relatives: pooled proportions with patient-mediated contact (A) and direct relative contact (B).
FIG A1.
FIG A1.
Funnel plots for genetic counseling and genetic testing outcomes. (A) Cascade genetic counseling, and (B) cascade genetic testing.
See this image and copyright information in PMC

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References

    1. Tuffaha HW, Mitchell A, Ward RL, et al. : Cost-effectiveness analysis of germ-line BRCA testing in women with breast cancer and cascade testing in family members of mutation carriers. Genet Med 20:985-994, 2018 - PubMed
    1. Committee on Gynecologic Practice : ACOG Committee Opinion No. 727: Cascade testing: Testing women for known hereditary genetic mutations associated with cancer. Obstet Gynecol 131:e31-e34, 2018 - PubMed
    1. Randall LM, Pothuri B, Swisher EM, et al. : Multi-disciplinary summit on genetics services for women with gynecologic cancers: A Society of Gynecologic Oncology White Paper. Gynecol Oncol 146:217-224, 2017 - PubMed
    1. Offit K: The future of clinical cancer genomics. Semin Oncol 43:615-622, 2016 - PMC - PubMed
    1. Finch AP, Lubinski J, Møller P, et al. : Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J Clin Oncol 32:1547-1553, 2014 - PMC - PubMed

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