Implication and Influence of Multigene Panel Testing with Genetic Counseling in Korean Patients with BRCA1/2 Mutation-Negative Breast Cancer
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Purpose: The aim of the study was to evaluate the clinical implication of multigene panel testing of beyond BRCA genes in Korean patients with BRCA1/2 mutation-negative breast cancer. Materials and methods: Between 2016 and 2019, a total of 700 BRCA1/2 mutation-negative breast cancer patients received comprehensive multigene panel testing and genetic counseling. Among them, 347 patients completed a questionnaire about cancer worry, genetic knowledge, and preference for the method of genetic tests during pre- and post-genetic test counseling. The frequency of pathogenic and likely pathogenic variants (PV/LPV) were analyzed. Results: At least one PV/LPV of 26 genes was found in 76 out of 700 patients (10.9 %). The rate for PV/LPV was 3.4% for high-risk genes (17 PALB2, 6 TP53, and 1 PTEN). PV/LPVs of clinical actionable genes for breast cancer management, high-risk genes and other moderate-risk genes such as ATM, BARD1, BRIP, CHEK2, NF1, and RAD51D, were observed in 7.4%. Patients who completed the questionnaire showed decreased concerns about the risk of additional cancer development (average score, 4.21 to 3.94; p < 0.001), influence on mood (3.27 to 3.13; p < 0.001), influence on daily functioning (3.03 to 2.94; p=0.006); and increased knowledge about hereditary cancer syndrome (66.9 to 68.8; p=0.025) in post-test genetic counseling. High cancer worry scales (CWSs) were associated with age ≤ 40 years and the identification of PV/LPV. Low CWSs were related to the satisfaction of the counselee. Conclusion: Comprehensive multigene panel test with genetic counseling is clinically applicable. It should be based on interpretable genetic information, consideration of potential psychological consequences, and proper preventive strategies.
Abstract
Purpose: The aim of the study was to evaluate the clinical implication of multigene panel testing of beyond BRCA genes in Korean patients with BRCA1/2 mutation-negative breast cancer. Materials and methods: Between 2016 and 2019, a total of 700 BRCA1/2 mutation-negative breast cancer patients received comprehensive multigene panel testing and genetic counseling. Among them, 347 patients completed a questionnaire about cancer worry, genetic knowledge, and preference for the method of genetic tests during pre- and post-genetic test counseling. The frequency of pathogenic and likely pathogenic variants (PV/LPV) were analyzed. Results: At least one PV/LPV of 26 genes was found in 76 out of 700 patients (10.9 %). The rate for PV/LPV was 3.4% for high-risk genes (17 PALB2, 6 TP53, and 1 PTEN). PV/LPVs of clinical actionable genes for breast cancer management, high-risk genes and other moderate-risk genes such as ATM, BARD1, BRIP, CHEK2, NF1, and RAD51D, were observed in 7.4%. Patients who completed the questionnaire showed decreased concerns about the risk of additional cancer development (average score, 4.21 to 3.94; p < 0.001), influence on mood (3.27 to 3.13; p < 0.001), influence on daily functioning (3.03 to 2.94; p=0.006); and increased knowledge about hereditary cancer syndrome (66.9 to 68.8; p=0.025) in post-test genetic counseling. High cancer worry scales (CWSs) were associated with age ≤ 40 years and the identification of PV/LPV. Low CWSs were related to the satisfaction of the counselee. Conclusion: Comprehensive multigene panel test with genetic counseling is clinically applicable. It should be based on interpretable genetic information, consideration of potential psychological consequences, and proper preventive strategies.
참고문헌 (37)
- Kuchenbaecker KB, "Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers", JAMA, 317, pp.2402~2416 (2017)
- Chen S, "Meta-analysis of BRCA1 and BRCA2 penetrance", J Clin Oncol, 25, pp.1329~1333 (2007)
- Mavaddat N, "Cancer risks for BRCA1 and BRCA2 mutation carriers : results from prospective analysis of EMBRACE", J Natl Cancer Inst, 105, pp.812~822 (2013)
- Paluch-Shimon S, "Prevention and screening in BRCA mutation carriers and other breast", ovarian hereditary cancer syndromes : ESMO Clinical Practice Guidelines for cancer prevention and screening, 2016, pp.27, v103~v110
- US Preventive Services Task Force, "Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer : US Preventive Services Task Force recommendation statement", JAMA, 322, pp.652~665 (2019)
- Tung NM, "Management of hereditary breast cancer : American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology guideline", J Clin Oncol, 38, pp.2080~2106 (2020)
- Daly MB, "Genetic", familial high-risk assessment: breast, ovarian, and pancreatic, version 2.2021, NCCN Clinical Practice Guidelines in Oncology, 2021, pp.19, 77~102
- Katz SJ, "Association of germline genetic test type and results with patient cancer worry after diagnosis of breast cancer", JCO Precis Oncol, 2018, pp.PO.18.0022~ (2018)
- Obeid EI, "Multigene panel testing and breast cancer risk : is it time to scale down?", JAMA Oncol, 3, pp.1176~1177 (2017)
- Plagnol V, "A robust model for read count data in exome sequencing experiments and implications for copy number variant calling", Bioinformatics, 28, pp.2747~2754 (2012)
- Richards S, "Standards and guidelines for the interpretation of sequence variants : a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology", Genet Med, 17, pp.405~424 (2015)
- Plon SE, "Sequence variant classification and reporting : recommendations for improving the interpretation of cancer susceptibility genetic test results", Hum Mutat, 29, pp.1282~1291 (2008)
- Desmond A, "Clinical actionability of multigene panel testing for hereditary breast and ovarian cancer risk assessment", JAMA Oncol, 1, pp.943~951 (2015)
- Foulkes WD, "Inherited susceptibility to common cancers", N Engl J Med, 359, pp.2143~2153 (2008)
- Shiovitz S, "Genetics of breast cancer : a topic in evolution", Ann Oncol, 26, pp.1291~1299 (2015)
- Tung N, "Counselling framework for moderate-penetrance cancer-susceptibility mutations", Nat Rev Clin Oncol, 13, pp.581~588 (2016)
- Lerman C, "Attitudes about genetic testing for breast-ovarian cancer susceptibility", J Clin Oncol, 12, pp.843~850 (1994)
- Choi E, "Relationship between cancer worry and stages of adoption for breast cancer screening among Korean women", PLoS One, 10, pp.e0132351~ (2015)
- Anh Thi Ngoc Tran, "Impact of Awareness of Breast Density on Perceived Risk, Worry, and Intentions for Future Breast Cancer Screening among Korean Women", Cancer Research and Treatment, 53(1), pp.55~64 (2021), 대한암학회[DOI]
- Erblich J, "Development and validation of a Breast Cancer Genetic Counseling Knowledge Questionnaire", Patient Educ Couns, 56, pp.182~191 (2005)
- 최경숙, "국내 간호사의 유전성 유방암에 대한 지식정도 조사연구", 한국간호교육학회지, 12(2), pp.272~179 (2006), 한국간호교육학회
- 이상희, "장액성 난소암 환자의 유전성 난소암에 대한 지식 및 불안정도", 여성건강간호학회지, 25(4), pp.365~378 (2019), 한국여성건강간호학회[DOI]
- Kurian AW, "Clinical evaluation of a multiple-gene sequencing panel for hereditary cancer risk assessment", J Clin Oncol, 32, pp.2001~2009 (2014)
- Castera L, "Landscape of pathogenic variations in a panel of 34 genes and cancer risk estimation from 5131 HBOC families", Genet Med, 20, pp.1677~1686 (2018)
- Couch FJ, "Associations between cancer predisposition testing panel genes and breast cancer", JAMA Oncol, 3, pp.1190~1196 (2017)
- Hauke J, "Gene panel testing of 5589 BRCA1", 2-negative index patients with breast cancer in a routine diagnostic setting : results of the German Consortium for Hereditary Breast and Ovarian Cancer, 2018, pp.7, 1349~1358
- Hu C, "A population-based study of genes previously implicated in breast cancer", N Engl J Med, 384, pp.440~451 (2021)
- Zhou J, "Spectrum of PALB2 germline mutations and characteristics of PALB2-related breast cancer : screening of 16, 501 unselected patients with breast cancer and 5890 controls by next-generation sequ-encing", Cancer, 126, pp.3202~3208 (2020)
- Li FP, "A cancer family syndrome in twenty-four kindreds", Cancer Res, 48, pp.5358~5362 (1988)
- Birch JM, "Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families", Cancer Res, 54, pp.1298~1304 (1994)
- Eeles RA, "Germline mutations in the TP53 gene", Cancer Surv, 25, pp.101~124 (1995)
- Bougeard G, "Revisiting Li-Fraumeni syndrome from TP53 mutation carriers", J Clin Oncol, 33, pp.2345~2352 (2015)
- Braithwaite D, "Psychological impact of genetic counseling for familial cancer : a systematic review and meta-analysis", J Natl Cancer Inst, 96, pp.122~133 (2004)
- Richter S, "Variants of unknown significance in BRCA testing: impact on risk perception, worry, prevention and counseling", Ann Oncol, 24(Suppl 8), pp.viii69~viii74 (2013)
- Mighton C, "Clinical and psychological outcomes of receiving a variant of uncertain significance from multigene panel testing or genomic sequencing : a systematic review and meta-analysis", Genet Med, 23, pp.22~33 (2021)
- Fraser FC, "Genetic counseling", Am J Hum Genet, 26, pp.636~659 (1974)
- Biesecker BB, "Goals of genetic counseling", Clin Genet, 60, pp.323~330 (2001)
