Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting BRCA1/2 mutations in a Southeast Asian country
Background : Germline mutations in the BRCA1 and BRCA2 genes have significant clinical implications for both risk-reducing and early surveillance management. The third and most recent revision of the Manchester scoring system (MSS3) used to distinguish patients indicated for germline BRCA1/2 testing...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2019
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| Online Access: | https://hdl.handle.net/10356/85532 http://hdl.handle.net/10220/49224 |
| _version_ | 1811678719725535232 |
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| author | Chew, Winston Moorakonda, Rajesh Babu Courtney, Eliza Soh, Hazel Li, Shao Tzu Chen, Yanni Shaw, Tarryn Allen, John Carson Evans, Dafydd Gareth R. Ngeow, Joanne |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Chew, Winston Moorakonda, Rajesh Babu Courtney, Eliza Soh, Hazel Li, Shao Tzu Chen, Yanni Shaw, Tarryn Allen, John Carson Evans, Dafydd Gareth R. Ngeow, Joanne |
| author_sort | Chew, Winston |
| collection | NTU |
| description | Background : Germline mutations in the BRCA1 and BRCA2 genes have significant clinical implications for both risk-reducing and early surveillance management. The third and most recent revision of the Manchester scoring system (MSS3) used to distinguish patients indicated for germline BRCA1/2 testing included further adjustments for triple negative breast cancer, high-grade serous ovarian cancer and human epidermal growth factor 2 (HER2) receptor status. This study aims to evaluate the relative effectiveness of MSS3 in a Southeast Asian population. Methods : All patients in our centre were tested using next-generation sequencing (NGS) panels that included full gene sequencing as well as coverage for large deletions/duplications in BRCA1/2. We calculated MSS1-3 scores for index patients between 2014 and 2017 who had undergone BRCA1/2 genetic testing and recorded their genetic test results. MSS1-3 outcomes were compared using receiver operating characteristic analysis, while associations with predictors were investigated using Fisher’s exact test and logistics regression. Calculations were performed using Medcalc17. Results : Of the 330 included patients, 47 (14.2%) were found to have a germline mutation in BRCA1 or BRCA2. A positive HER2 receptor was associated with a lower likelihood of a BRCA1/2mutation (OR=0.125, 95% CI 0.016 to 0.955; P=0.007), while high-grade serous ovarian cancer was conversely associated with an increased likelihood of a BRCA1/2 mutation (OR=5.128, 95% CI 1.431 to 18.370; P=0.012). At the 10% threshold, 43.0% (142/330) of patients were indicated for testing under MSS3, compared with 35.8% (118/330) for MSS1% and 36.4% (120/330) for MSS2. At the 10% threshold, MSS3 sensitivity was 91.5% and specificity 65.0%, significantly better than the previous MSS1 (P=0.037) and MSS2 (P=0.032) models. Conclusion : Our results indicate that the updated MSS3 outperforms previous iterations and relative to the Manchester population, is just as effective in identifying patients with BRCA1/2 mutations in a Southeast Asian population. |
| first_indexed | 2024-10-01T02:57:44Z |
| format | Journal Article |
| id | ntu-10356/85532 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:57:44Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/855322020-03-07T12:57:23Z Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting BRCA1/2 mutations in a Southeast Asian country Chew, Winston Moorakonda, Rajesh Babu Courtney, Eliza Soh, Hazel Li, Shao Tzu Chen, Yanni Shaw, Tarryn Allen, John Carson Evans, Dafydd Gareth R. Ngeow, Joanne Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine BRCA 1 HER2 Receptor Background : Germline mutations in the BRCA1 and BRCA2 genes have significant clinical implications for both risk-reducing and early surveillance management. The third and most recent revision of the Manchester scoring system (MSS3) used to distinguish patients indicated for germline BRCA1/2 testing included further adjustments for triple negative breast cancer, high-grade serous ovarian cancer and human epidermal growth factor 2 (HER2) receptor status. This study aims to evaluate the relative effectiveness of MSS3 in a Southeast Asian population. Methods : All patients in our centre were tested using next-generation sequencing (NGS) panels that included full gene sequencing as well as coverage for large deletions/duplications in BRCA1/2. We calculated MSS1-3 scores for index patients between 2014 and 2017 who had undergone BRCA1/2 genetic testing and recorded their genetic test results. MSS1-3 outcomes were compared using receiver operating characteristic analysis, while associations with predictors were investigated using Fisher’s exact test and logistics regression. Calculations were performed using Medcalc17. Results : Of the 330 included patients, 47 (14.2%) were found to have a germline mutation in BRCA1 or BRCA2. A positive HER2 receptor was associated with a lower likelihood of a BRCA1/2mutation (OR=0.125, 95% CI 0.016 to 0.955; P=0.007), while high-grade serous ovarian cancer was conversely associated with an increased likelihood of a BRCA1/2 mutation (OR=5.128, 95% CI 1.431 to 18.370; P=0.012). At the 10% threshold, 43.0% (142/330) of patients were indicated for testing under MSS3, compared with 35.8% (118/330) for MSS1% and 36.4% (120/330) for MSS2. At the 10% threshold, MSS3 sensitivity was 91.5% and specificity 65.0%, significantly better than the previous MSS1 (P=0.037) and MSS2 (P=0.032) models. Conclusion : Our results indicate that the updated MSS3 outperforms previous iterations and relative to the Manchester population, is just as effective in identifying patients with BRCA1/2 mutations in a Southeast Asian population. 2019-07-09T09:12:02Z 2019-12-06T16:05:28Z 2019-07-09T09:12:02Z 2019-12-06T16:05:28Z 2018 Journal Article Chew, W., Moorakonda, R. B., Courtney, E., Soh, H., Li, S. T., Chen, Y., . . . Ngeow, J. (2018). Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting BRCA1/2 mutations in a Southeast Asian country. Journal of Medical Genetics, 55(5), 344-350. doi:10.1136/jmedgenet-2017-105073 0022-2593 https://hdl.handle.net/10356/85532 http://hdl.handle.net/10220/49224 10.1136/jmedgenet-2017-105073 en Journal of Medical Genetics |
| spellingShingle | Science::Medicine BRCA 1 HER2 Receptor Chew, Winston Moorakonda, Rajesh Babu Courtney, Eliza Soh, Hazel Li, Shao Tzu Chen, Yanni Shaw, Tarryn Allen, John Carson Evans, Dafydd Gareth R. Ngeow, Joanne Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting BRCA1/2 mutations in a Southeast Asian country |
| title | Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting
BRCA1/2
mutations in a Southeast Asian country |
| title_full | Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting
BRCA1/2
mutations in a Southeast Asian country |
| title_fullStr | Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting
BRCA1/2
mutations in a Southeast Asian country |
| title_full_unstemmed | Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting
BRCA1/2
mutations in a Southeast Asian country |
| title_short | Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting
BRCA1/2
mutations in a Southeast Asian country |
| title_sort | evaluation of the relative effectiveness of the 2017 updated manchester scoring system for predicting brca1 2 mutations in a southeast asian country |
| topic | Science::Medicine BRCA 1 HER2 Receptor |
| url | https://hdl.handle.net/10356/85532 http://hdl.handle.net/10220/49224 |
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