Cascade Genetic Testing for Hereditary Cancer Risk: An Underutilized Tool for Cancer Prevention

Whitaker, Katrine B.; Obeid, Elias; Daly, Mary B.; Hall, Michael J.

doi:10.1200/po.21.00163

Cited by 35 publications

(17 citation statements)

References 83 publications

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“…Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer that cascade testing in clinical practice is lacking. 16,37,38 In addition to supporting germline genetic testing for all patients with a cancer diagnosis, the recent report from the President's Cancer Panel states that cascade testing should be offered if variants of concern are identified. 39…”

Section: Jama Network Open | Oncologymentioning

confidence: 99%

Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer

et al. 2022

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ImportanceNational Comprehensive Cancer Network guidelines currently recommend germline testing for high-risk genes in selected patients with breast cancer. The clinical utility of recommending testing all patients with breast cancer with multigene panels is currently under consideration.ObjectiveTo examine the implications of universal testing of patients with breast cancer with respect to clinical decision-making.Design, Setting, and ParticipantsPatients from a previously reported cohort were assessed as in-criteria or out-of-criteria according to the 2017 guidelines and underwent testing with a multigene germline panel between 2017 to 2018. Patients were women and men aged 18 to 90 years, with a new and/or previous diagnosis of breast cancer who had not undergone either single or multigene testing. Clinicians from 20 community and academic sites documented patient clinical information and changes to clinical recommendations made according to test findings. Association between prevalence of pathogenic or likely pathogenic germline variants and previously unreported clinical features, including scores generated by the BRCAPRO statistical model, was determined. Data were analyzed from April 2020 to May 2022.ExposureNew and/or previous diagnosis of breast cancer.Main Outcomes and MeasuresDisease management recommendations that were changed as a result of genetic testing results are reported.ResultsClinicians were asked to assess changes to clinical management as a result of germline genetic testing for 952 patients. Informative clinician-reported recommendations were provided for 939 (467 in-criteria and 472 out-of-criteria) of the patients with breast cancer (936 [99.7%] female; 702 [74.8%] White; mean [SD] age at initial diagnosis, 57.6 [11.5] years). One or more changes were reported for 31 of 37 (83.8%) in-criteria patients and 23 of 34 (67.6%) out-of-criteria patients with a pathogenic or likely pathogenic variant. Recommendations were changed as a result of testing results for 14 of 22 (63.6%) out-of-criteria patients who had a variant in a breast cancer predisposition gene. Clinicians considered testing beneficial for two-thirds of patients with pathogenic or likely pathogenic variants and for one-third of patients with either negative results or variants of uncertain significance. There was no difference in variant rate between patients meeting the BRCAPRO threshold (≥10%) and those who did not (P = .86, Fisher exact test). No changes to clinical recommendations were made for most patients with negative results (345 of 349 patients [98.9%]) or variants of uncertain significance (492 of 509 patients [96.7%]).Conclusions and RelevanceIn this cohort study, germline genetic testing was used by clinicians to direct treatment for most out-of-criteria patients with breast cancer with pathogenic or likely pathogenic germline variants, including those with moderate-risk variants. Universal germline testing informs clinical decision-making and provides access to targeted treatments and clinical trials for all patients with breast cancer.

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Section: Jama Network Open | Oncologymentioning

confidence: 99%

Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer

et al. 2022

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“…Several initiatives and trials that involved offering full [ 22 ] or partially cost-free testing [ 23 , 24 ], online invitations [ 23 ], mailing of saliva kits to relatives following telephone counseling [ 25 ], and pre-testing counseling to the entire family [ 26 ] did not increase the rates of cascade screening above what has been reported in observational studies. Moreover, most studies report an uptake of genetic testing primarily among first-degree relatives (FDR), who are more likely to be invited and to accept testing [ 27 ]. The aforementioned trials also report rates of cascade testing based on responses from index cases, which can be erroneous due to recall and social desirability bias [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Relatives from Hereditary Breast and Ovarian Cancer and Lynch Syndrome Families Forgoing Genetic Testing: Findings from the Swiss CASCADE Cohort

Sarki¹,

Ming²,

Aceti³

et al. 2022

JPM

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Cascade genetic testing of relatives from families with pathogenic variants associated with hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS) has important implications for cancer prevention. We compared the characteristics of relatives from HBOC or LS families who did not have genetic testing (GT (−) group) with those who had genetic testing (GT (+) group), regardless of the outcome. Self-administered surveys collected cross-sectional data between September 2017 and December 2021 from relatives participating in the CASCADE cohort. We used multivariable logistic regression with LASSO variable selection. Among n = 115 relatives who completed the baseline survey, 38% (n = 44) were in the GT (−) group. Being male (OR: 2.79, 95% CI: 1.10–7.10) and without a previous cancer diagnosis (OR: 4.47, 95% CI: 1.03–19.42) increased the odds of being untested by almost three times. Individuals from families with fewer tested relatives had 29% higher odds of being untested (OR: 0.71, 95% CI: 0.55–0.92). Reasons for forgoing cascade testing were: lack of provider recommendation, lack of time and interest in testing, being afraid of discrimination, and high out-of-pocket costs. Multilevel interventions designed to increase awareness about clinical implications of HBOC and LS in males, referrals from non-specialists, and support for testing multiple family members could improve the uptake of cascade testing.

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“…Uptake of cascade screening in families with known pathogenic variants associated with hereditary breast and ovarian cancer or Lynch syndrome continues to be suboptimal, due in part to incomplete notification of at-risk relatives. Approaches to support patient-led risk notification, the current US standard, may help to improve risk notification [ 21 ], subsequent uptake of cascade testing, and improved cancer outcomes [ 22 ]. A more disruptive and potentially more effective strategy to improve rates of relative notification involves direct contact of relatives by health systems; this is the intervention under exploration in the Lynx study.…”

Section: Discussionmentioning

confidence: 99%

Feasibility, acceptability, and limited efficacy of health system-led familial risk notification: protocol for a mixed-methods evaluation

Blasi

Scrol

Anderson

et al. 2022

Pilot Feasibility Stud

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Background Genetic testing for pathogenic variants associated with hereditary breast and ovarian cancer risk can improve cancer outcomes through enhanced preventive care in both people with known variants and their biologic relatives. Cascade screening—the process of case-finding in relatives by notifying and inviting them to consider testing—currently relies on the patient to notify their own at-risk relatives. However, many of these relatives never learn they might be at risk. We developed and implemented a new health system-led familial genetic risk notification process where the care team offers to contact at-risk relatives directly. This protocol describes a study to assess the feasibility, acceptability, and limited efficacy of this intervention. Methods This feasibility study will use a single-arm, nonrandomized, mixed-methods prospective design. We will enroll two groups of participants: probands and relatives of probands. Eligible probands are currently enrolled Kaiser Permanente Washington (KPWA) members with an upcoming appointment for pre-test genetic counseling for hereditary Lynch syndrome, breast, or ovarian cancer. Eligible relatives, who do not have to be KPWA members, are first-and second-degree relatives of probands. During the appointment with the proband, the genetic counselor will determine whether the proband is appropriate for genetic testing and if so, which relatives might benefit from cascade testing. The genetic counselor then will offer to contact any or all identified relatives directly to discuss genetic risk and testing. The primary outcome of this study is the feasibility of the implemented familial notification process, which we will measure using quantitative and qualitative data on intervention reach, intervention acceptability, and limited efficacy. Analyses will be primarily descriptive and exploratory, with the intent of preparing for a future, larger trial of direct contact interventions. Discussion Our findings will provide new, foundational evidence for the creation of US-based familial notification systems that directly address logistical and ethical challenges while prioritizing the preferences of patients and families.

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Cascade Genetic Testing for Hereditary Cancer Risk: An Underutilized Tool for Cancer Prevention

Abstract: Author affiliations and support information (if applicable) appear at the end of this article.

Cited by 35 publications

References 83 publications

Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer

Clinical Utility of Universal Germline Genetic Testing for Patients With Breast Cancer

Relatives from Hereditary Breast and Ovarian Cancer and Lynch Syndrome Families Forgoing Genetic Testing: Findings from the Swiss CASCADE Cohort

Feasibility, acceptability, and limited efficacy of health system-led familial risk notification: protocol for a mixed-methods evaluation

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