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      Psychosocial outcomes following germline multigene panel testing in an ethnically and economically diverse cohort of patients

      research-article
      , MS 1 , , , MS 1 , , PhD 2 , , MS 3 , , MSN 2 , , MS 4 , , MS 4 , , MS 1 , , MS 4 , , MS 4 , , MS 4 , , MS 4 , , MS 1 , , PhD, MS 4 , , MS 2 , , MS 2 , , BA 4 , , PhD 3 , , PhD 1 , , MD 4 , , MD, PhD 2 , , MD 4 , , MD, PhD, MPH 2 , , MD, MSc 4 , , MD, MS 2 ,
      Cancer
      John Wiley and Sons Inc.
      genetic counseling, genetic techniques, genetic testing, hereditary neoplastic syndromes, psycho‐oncology, psychosocial factors

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          Abstract

          Background

          Little is known about the psychological outcomes of germline multigene panel testing, particularly among diverse patients and those with moderate‐risk pathogenic variants (PVs).

          Methods

          Study participants (N = 1264) were counseled and tested with a 25‐ or 28‐gene panel and completed a 3‐month postresult survey including the Multidimensional Impact of Cancer Risk Assessment (MICRA).

          Results

          The mean age was 52 years, 80% were female, and 70% had cancer; 45% were non‐Hispanic White, 37% were Hispanic, 10% were Asian, 3% were Black, and 5% had another race/ethnicity. Approximately 28% had a high school education or less, and 23% were non–English‐speaking. The genetic test results were as follows: 7% had a high‐risk PV, 6% had a moderate‐risk PV, 35% had a variant of uncertain significance (VUS), and 52% were negative. Most participants (92%) had a total MICRA score ≤ 38, which corresponded to a mean response of “never,” “rarely,” or only “sometimes” reacting negatively to results. A multivariate analysis found that mean total MICRA scores were significantly higher (more uncertainty/distress) among high‐ and moderate‐risk PV carriers (29.7 and 24.8, respectively) than those with a VUS or negative results (17.4 and 16.1, respectively). Having cancer or less education was associated with a significantly higher total MICRA score; race/ethnicity was not associated with the total MICRA score. High‐ and moderate‐risk PV carriers did not differ significantly from one another in the total MICRA score, uncertainty, distress, or positive experiences.

          Conclusions

          In a diverse population undergoing genetic counseling and multigene panel testing for hereditary cancer risk, the psychological response corresponded to test results and showed low distress and uncertainty. Further studies are needed to assess patient understanding and subsequent cancer screening among patients from diverse backgrounds.

          Lay Summary

          • Multigene panel tests for hereditary cancer have become widespread despite concerns about adverse psychological reactions among carriers of moderate‐risk pathogenic variants (mutations) and among carriers of variants of uncertain significance.

          • This large study of an ethnically and economically diverse cohort of patients undergoing panel testing found that 92% “never,” “rarely,” or only “sometimes” reacted negatively to results.

          • Somewhat higher uncertainty and distress were identified among carriers of high‐ and moderate‐risk pathogenic variants, and lower levels were identified among those with a variant of uncertain significance or a negative result.

          • Although the psychological response corresponded to risk, reactions to testing were favorable, regardless of results.

          Abstract

          Multigene panel tests for hereditary cancer have become widespread despite concerns that carriers of moderate‐risk pathogenic variants or uncertain variants could have adverse psychological reactions. This large cohort study of patients undergoing panel testing has found that the psychological response is favorable, regardless of genetic test results.

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          Most cited references28

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          NCCN Guidelines Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 1.2020

          The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic provide recommendations for genetic testing and counseling for hereditary cancer syndromes, and risk management recommendations for patients who are diagnosed with syndromes associated with an increased risk of these cancers. The NCCN panel meets at least annually to review comments, examine relevant new data, and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel’s discussion and most recent recommendations regarding criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2 , pancreas screening and genes associated with pancreatic cancer, genetic testing for the purpose of systemic therapy decision-making, and testing for people with Ashkenazi Jewish ancestry.
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            Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment.

            The practice of genetic testing for hereditary breast and/or ovarian cancer (HBOC) is rapidly evolving owing to the recent introduction of multigene panels. While these tests may identify 40% to 50% more individuals with hereditary cancer gene mutations than does testing for BRCA1/2 alone, whether finding such mutations will alter clinical management is unknown.
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              • Article: not found

              Germline and Somatic Tumor Testing in Epithelial Ovarian Cancer: ASCO Guideline

              To provide recommendations on genetic and tumor testing for women diagnosed with epithelial ovarian cancer based on available evidence and expert consensus. A literature search and prospectively defined study selection criteria sought systematic reviews, meta-analyses, randomized controlled trials (RCTs), and comparative observational studies published from 2007 through 2019. Guideline recommendations were based on the review of the evidence. The systematic review identified 19 eligible studies. The evidence consisted of systematic reviews of observational data, consensus guidelines, and RCTs. All women diagnosed with epithelial ovarian cancer should have germline genetic testing for BRCA1/2 and other ovarian cancer susceptibility genes. In women who do not carry a germline pathogenic or likely pathogenic BRCA1/2 variant, somatic tumor testing for BRCA1/2 pathogenic or likely pathogenic variants should be performed. Women with identified germline or somatic pathogenic or likely pathogenic variants in BRCA1/2 genes should be offered treatments that are US Food and Drug Administration (FDA) approved in the upfront and the recurrent setting. Women diagnosed with clear cell, endometrioid, or mucinous ovarian cancer should be offered somatic tumor testing for mismatch repair deficiency (dMMR). Women with identified dMMR should be offered FDA-approved treatment based on these results. Genetic evaluations should be conducted in conjunction with health care providers familiar with the diagnosis and management of hereditary cancer. First- or second-degree blood relatives of a patient with ovarian cancer with a known germline pathogenic cancer susceptibility gene variant should be offered individualized genetic risk evaluation, counseling, and genetic testing. Clinical decision making should not be made based on a variant of uncertain significance. Women with epithelial ovarian cancer should have testing at the time of diagnosis.
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                Author and article information

                Contributors
                jculver@med.usc.edu
                gidos@coh.org
                Journal
                Cancer
                Cancer
                10.1002/(ISSN)1097-0142
                CNCR
                Cancer
                John Wiley and Sons Inc. (Hoboken )
                0008-543X
                1097-0142
                15 December 2020
                15 April 2021
                : 127
                : 8 ( doiID: 10.1002/cncr.v127.8 )
                : 1275-1285
                Affiliations
                [ 1 ] USC Norris Comprehensive Cancer Center University of Southern California Los Angeles California
                [ 2 ] Center for Precision Medicine City of Hope National Medical Center and Beckman Research Institute Duarte California
                [ 3 ] Myriad Genetics Salt Lake City Utah
                [ 4 ] Stanford University School of Medicine Stanford California
                Author notes
                [*] [* ] Corresponding Authors: Julie O. Culver, MS, Cancer Genetics Program, USC Norris Comprehensive Cancer Center, University of Southern California, 1450 Biggy St, #2509L, Los Angeles, CA 90033 ( jculver@ 123456med.usc.edu ); Gregory E. Idos, MD, MS, Center for Precision Medicine, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010 ( gidos@ 123456coh.org ).

                Author information
                https://orcid.org/0000-0001-8658-3507
                https://orcid.org/0000-0003-2887-4079
                https://orcid.org/0000-0003-0665-8797
                https://orcid.org/0000-0002-2513-7025
                https://orcid.org/0000-0002-6175-9470
                Article
                CNCR33357
                10.1002/cncr.33357
                8058169
                33320347
                e0ed2693-b5ab-4474-823d-e55ec22b070a
                © 2020 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 28 September 2020
                : 22 July 2020
                : 24 October 2020
                Page count
                Figures: 4, Tables: 3, Pages: 11, Words: 7679
                Funding
                Funded by: Myriad Genetics
                Award ID: HCP‐005
                Funded by: National Cancer Institute
                Award ID: P30 CA14089
                Award ID: R01 CA197350
                Award ID: R35 CA197461
                Funded by: National Institutes of Health
                Award ID: KL2 TR000131
                Funded by: Jane and Kris Popovich
                Award ID: Chair in Cancer Research
                Funded by: Daniel and Maryann Fong
                Funded by: Anton B. Burg Foundation
                Categories
                Original Article
                Original Articles
                Discipline
                Cancer Prevention
                Custom metadata
                2.0
                April 15, 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:01.07.2021

                Oncology & Radiotherapy
                genetic counseling,genetic techniques,genetic testing,hereditary neoplastic syndromes,psycho‐oncology,psychosocial factors

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