domingo, 7 de enero de 2018

Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting BRCA1/2 mutations in a Southeast Asian country. - PubMed - NCBI

2017 Dec 23. pii: jmedgenet-2017-105073. doi: 10.1136/jmedgenet-2017-105073. [Epub ahead of print]

Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting BRCA1/2 mutations in a Southeast Asian country.

Chew W1, Moorakonda RB2,3, Courtney E1, Soh H1, Li ST1, Chen Y1, Shaw T1, Allen JC2, Evans DGR4, Ngeow J1,5,6,7.

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Abstract

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.