Article Text

Download PDFPDF
Original Article
Evaluation of the relative effectiveness of the 2017 updated Manchester scoring system for predicting BRCA1/2 mutations in a Southeast Asian country
  1. Winston Chew1,
  2. Rajesh Babu Moorakonda2,3,
  3. Eliza Courtney1,
  4. Hazel Soh1,
  5. Shao Tzu Li1,
  6. Yanni Chen1,
  7. Tarryn Shaw1,
  8. John Carson Allen2,
  9. Dafydd Gareth R Evans4,
  10. Joanne Ngeow1,5,6,7
  1. 1 Division of Medical Oncology, National Cancer Centre Singapore, Cancer Genetics Service, Singapore, Singapore
  2. 2 Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore
  3. 3 Singapore Clinical Research Institute, Singapore, Singapore
  4. 4 Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Central Manchester University Hospitals NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK
  5. 5 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
  6. 6 Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore
  7. 7 Institute of Molecular and Cell Biology, Agency for Science Technology and Research (A*Star), Singapore, Singapore
  1. Correspondence to Dr Joanne Ngeow, Division of Medical Oncology, National Cancer Centre Singapore, Cancer Genetics Service, Singapore 169610, Singapore; joanne.ngeow.y.y{at}


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.

  • brca
  • cancer: breast
  • ovarian cancer
  • genetic testing
  • asian

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Contributors Design and conception of study: WC, DGRE, EC, JN. Statistical analysis: WC, RBM, JCA, DGRE. Data collection and clinical review: EC, HS, STL, YC, TS, JN. Critical review and revision of manuscript : all authors.

  • Competing interests None declared.

  • Ethics approval Singhealth Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement There was no additional unpublished data from this study.