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

      , 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 references 28

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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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            Multiplex genetic testing for cancer susceptibility: out on the high wire without a net?

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              • Article: not found

              Uptake, Results, and Outcomes of Germline Multiple-Gene Sequencing After Diagnosis of Breast Cancer

              Importance Low-cost sequencing of multiple genes is increasingly available for cancer risk assessment. Little is known about uptake or outcomes of multiple-gene sequencing after breast cancer diagnosis in community practice. Objective To examine the effect of multiple-gene sequencing on the experience and treatment outcomes for patients with breast cancer. Design, Setting, and Participants For this population-based retrospective cohort study, patients with breast cancer diagnosed from January 2013 to December 2015 and accrued from SEER registries across Georgia and in Los Angeles, California, were surveyed (n = 5080, response rate = 70%). Responses were merged with SEER data and results of clinical genetic tests, either BRCA1 and BRCA2 ( BRCA1/2 ) sequencing only or including additional other genes (multiple-gene sequencing), provided by 4 laboratories. Main Outcomes and Measures Type of testing (multiple-gene sequencing vs BRCA1/2 -only sequencing), test results (negative, variant of unknown significance, or pathogenic variant), patient experiences with testing (timing of testing, who discussed results), and treatment (strength of patient consideration of, and surgeon recommendation for, prophylactic mastectomy), and prophylactic mastectomy receipt. We defined a patient subgroup with higher pretest risk of carrying a pathogenic variant according to practice guidelines. Results Among 5026 patients (mean [SD] age, 59.9 [10.7] years), 1316 (26.2%) were linked to genetic results from any laboratory. Multiple-gene sequencing increasingly replaced BRCA1/2 -only testing over time: in 2013, the rate of multiple-gene sequencing was 25.6% and BRCA1/2- only testing, 74.4%; in 2015 the rate of multiple-gene sequencing was 66.5% and BRCA1/2- only testing, 33.5%. Multiple-gene sequencing was more often ordered by genetic counselors (multiple-gene sequencing, 25.5% and BRCA1/2- only testing, 15.3%) and delayed until after surgery (multiple-gene sequencing, 32.5% and BRCA1/2- only testing, 19.9%). Multiple-gene sequencing substantially increased rate of detection of any pathogenic variant (multiple-gene sequencing: higher-risk patients, 12%; average-risk patients, 4.2% and BRCA1/2 -only testing: higher-risk patients, 7.8%; average-risk patients, 2.2%) and variants of uncertain significance, especially in minorities (multiple-gene sequencing: white patients, 23.7%; black patients, 44.5%; and Asian patients, 50.9% and BRCA1/2 -only testing: white patients, 2.2%; black patients, 5.6%; and Asian patients, 0%). Multiple-gene sequencing was not associated with an increase in the rate of prophylactic mastectomy use, which was highest with pathogenic variants in BRCA1/2 ( BRCA1/2 , 79.0%; other pathogenic variant, 37.6%; variant of uncertain significance, 30.2%; negative, 35.3%). Conclusions and Relevance Multiple-gene sequencing rapidly replaced BRCA1/2 -only testing for patients with breast cancer in the community and enabled 2-fold higher detection of clinically relevant pathogenic variants without an associated increase in prophylactic mastectomy. However, important targets for improvement in the clinical utility of multiple-gene sequencing include postsurgical delay and racial/ethnic disparity in variants of uncertain significance. This population-based cohort study examines the effect of multiple-gene sequencing on the experiences and treatment outcomes of patients with breast cancer. Question What are the results and outcomes of more comprehensive genetic sequencing after diagnosis of breast cancer? Findings In this population-based study, multiple-gene sequencing markedly replaced BRCA1- and BRCA2 -only tests and enabled 2-fold higher detection of clinically relevant pathogenic variants without an associated increase in prophylactic mastectomy. Multiple-gene sequencing was more often delayed postsurgery and yielded much higher rates of variants of uncertain significance, particularly in racial/ethnic minorities. Meaning Multiple-gene sequencing rapidly replaced more limited testing and enabled 2-fold higher detection of clinically relevant findings, but important targets for improvement include postsurgical delay and racial/ethnic disparity in variants of uncertain significance.
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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 ).

                Article
                CNCR33357
                10.1002/cncr.33357
                8058169
                33320347
                © 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.

                Page count
                Figures: 4, Tables: 3, Pages: 11, Words: 7679
                Product
                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

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