Speaker Abstract RCMM 2017: Dr. Edward Wong

Inherited breast cancer predisposition in Asians: multigene panel testing outcomes from Singapore

1Edward SY Wong, 1Sandhya Shekar, 2Marie Met-Domestici, 1Claire Chan, 1Melody Sze, 2,3,4Yoon Sim Yap, 5Steven G. Rozen, 2,6Min-Han Tan, 2,7Peter Ang, 2,3,4Joanne Ngeow and 1,8,9Ann SG Lee

1Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre Singapore, Singapore

2Division of Medical Oncology, National Cancer Centre Singapore, Singapore

3Oncology Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore

4Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

5Centre for Computational Biology, Duke-NUS Graduate Medical School, Singapore

6Division of Biodevices and Diagnostics, Institute for Bioengineering and Nanotechnology, Singapore

7OncoCare Cancer Centre, Mount Elizabeth Novena Specialist Centre, Singapore

8Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

9Office of Clinical and Academic Faculty Affairs, Duke-NUS Graduate Medical School, Singapore.

Background:  Genetic testing for germline mutations in breast cancer predisposition genes can potentially identify individuals who are at a high risk of developing breast and/or ovarian cancer. The lack of mutational information from the Asian population resulted in the slow adoptions of such testing methods. The objective of this study was to assess the use of custom made Next-Generation Sequencing (NGS) gene panels for breast cancer susceptibility genes in an Asian, multi-racial cohort.

Methods:  Tests were done on custom panel made for 25 cancer susceptibility genes and BRCA1/2 deletion/duplication analysis was also performed on 220 individuals. The selection criteria are as follow: (1) having a family history of breast and/or ovarian cancer in first- and/or second-degree relatives; (2) having breast and ovarian cancer in the same individual or bilateral breast cancer; (3) having early-onset breast cancer or ovarian cancer (≤40 years of age).

Results: In this study, 67 pathogenic variants in 66 (30.0%) patients were identified.  Of these, 19 (28.3%) occurred in BRCA1, 16 (23.9%) in BRCA2, 7 (10.4%) in PALB2, 6 (9.0%) in TP53, 2 (3.0%) in PTEN, 2 (3.0%) in CDH1 and 15 (22.4%) in other predisposition genes.  47.8% of pathogenic variants were in non-BRCA1/2 genes.  Of the 66 patients with pathogenic mutations, 63.6% (42/66) were under the age of 40 years.  Family history of breast and/or ovarian cancer is enriched in patients with BRCA1/2 pathogenic variants but less predictive for non-BRCA1/2 related pathogenic variations.  In addition, we detected a median of 3 variants of unknown significance (VUS) per gene (range 0.21).

Conclusion:  Custom NGS gene panel is feasible and useful for the detection of pathogenic mutations and should be done in the setting of a formal clinical cancer genetics service given the rate of VUS.