Cancer Res Treat.  2022 Oct;54(4):1099-1110. 10.4143/crt.2021.978.

Implication and Influence of Multigene Panel Testing with Genetic Counseling in Korean Patients with BRCA1/2 Mutation-Negative Breast Cancer

• Park JS
• Shin S
• Lee YJ
• Lee ST
• Nam EJ
• Han JW
• Lee SH
• Kim TI
• Park HS

• KMID: 2534189
• DOI: http://doi.org/10.4143/crt.2021.978

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.

Keyword

Breast neoplasms; Genetic testing; Multigene panels; Beyond; Cancer worry

Figure

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  Fig. 1 Result of germline multigene panel tests in BRCA mutation-negative patients with high risk for hereditary breast cancer (n=700). (A) Proportion of the patients according to the results. (B) Frequency of likely pathogenic/pathogenic genetic variants (genes, n=26; patients, n=76)a). VUS, variants of unknown significance. a)Three patients had two likely pathogenic/pathogenic variants simultaneously (RAD50 and PMS2, EPCAM and SDHA, and JAK2 and NTRK1).

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  Fig. 2 Result of the survey about genetic counseling on multigene panel testing (n=374). (A) Satisfaction about the information gained by genetic tests with counseling. (B) Preference of the sequence and method of genetic testing for BRCA1/2 mutation test and multigene test beyond BRCA.

Reference

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