Predicting the likelihood of carrying a BRCA1 or BRCA2 Mutation in Asian patients with breast cancer

Ang, Boon Hong and Ho, Weang Kee and Wijaya, Eldarina and Kwan, Pui Yoke and Ng, Pei Sze and Yoon, Sook Yee and Hasan, Siti Norhidayu and Lim, Joanna M. C. and Hassan, Tiara and Tai, Mei-Chee and Allen, Jamie and Lee, Andrew and Mohd Taib, Nur Aishah and Yip, Cheng Har and Hartman, Mikael and Lim, Swee Ho and Tan, Ern Yu and Tan, Benita K. T. and Tan, Su-Ming and Tan, Veronique K. M. and Ho, Peh Joo and Khng, Alexis J. and Dunning, Alison M. and Li, Jingmei and Easton, Douglas F. and Antoniou, Antonis C. and Teo, Soo Hwang (2022) Predicting the likelihood of carrying a BRCA1 or BRCA2 Mutation in Asian patients with breast cancer. Journal of Clinical Oncology, 40 (14). 1542+. ISSN 0732-183X, DOI

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PURPOSE With the development of poly (ADP-ribose) polymerase inhibitors for treatment of patients with cancer with an altered BRCA1 or BRCA2 gene, there is an urgent need to ensure that there are appropriate strategies for identifying mutation carriers while balancing the increased demand for and cost of cancer genetics services. To date, the majority of mutation prediction tools have been developed in women of European descent where the age and cancer-subtype distributions are different from that in Asian women. METHODS In this study, we built a new model (Asian Risk Calculator) for estimating the likelihood of carrying a pathogenic variant in BRCA1 or BRCA2 gene, using germline BRCA genetic testing results in a cross-sectional population-based study of 8,162 Asian patients with breast cancer. We compared the model performance to existing mutation prediction models. The models were evaluated for discrimination and calibration. RESULTS Asian Risk Calculator included age of diagnosis, ethnicity, bilateral breast cancer, tumor biomarkers, and family history of breast cancer or ovarian cancer as predictors. The inclusion of tumor grade improved significantly the model performance. The full model was calibrated (Hosmer-Lemeshow P value = .614) and discriminated well between BRCA and non-BRCA pathogenic variant carriers (area under receiver operating curve, 0.80; 95% CI, 0.75 to 0.84). Addition of grade to the existing clinical genetic testing criteria targeting patients with breast cancer age younger than 45 years reduced the proportion of patients referred for genetic counseling and testing from 37% to 33% (P value = .003), thereby improving the overall efficacy. CONCLUSION Population-specific customization of mutation prediction models and clinical genetic testing criteria improved the accuracy of BRCA mutation prediction in Asian patients.

Item Type: Article
Funders: None
Uncontrolled Keywords: BRCA1 protein; BRCA2 protein; Breast neoplasms; Cross-sectional studies; Female; Genes, BRCA2; Genetic predisposition to disease; Germ-line mutation; Humans; Middle aged; Mutation; Ovarian neoplasms
Subjects: R Medicine > RC Internal medicine
R Medicine > RD Surgery
Divisions: Faculty of Medicine > Surgery Department
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 01 Dec 2023 01:00
Last Modified: 01 Dec 2023 08:49

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