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Accuracy of BRCA1/2 mutation prediction models in Korean breast cancer patients

  • Epidemiology
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Abstract

BRCAPRO and Myriad II are widely used models for predicting BRCA1/2 mutation probability before genetic testing. However, the accuracy of these models in Koreans is not known. This study was performed to evaluate the accuracy of the BRCAPRO and Myriad II models. Two hundred thirty-six women with breast cancer who underwent comprehensive BRCA1/2 genetic testing at our hospital between 2003 and 2010 were included in this study. We evaluated the performance of each model by comparing the numbers of observed versus predicted mutation carriers. We calculated sensitivity, specificity, and predictive values at 10 % estimated probability. Forty-six individuals were identified to carry a deleterious BRCA mutation. The prevalence of BRCA mutation (19.5 %) was significantly higher than that predicted by BRCAPRO (9.0 %, p = 0.001) and Myriad (5.6 %, p < 0.001). In familial breast cancer patients, BRCA mutation rate (observed 22.7 %) was underestimated by both BRCAPRO (expected 11.4 %, p = 0.006) and Myriad II (expected 6.4 %, p < 0.001). Subgroup analyses showed that both models underestimated the risk of BRCA mutation in patients with a family history of breast cancer (probands’ age at breast cancer diagnosis >50 years), with only one relative with breast cancer, and with non-familial early-onset breast cancer or bilateral breast cancer. Using a 10 % cut-off, the sensitivities were 47.8 % (BRCAPRO) and 50.0 % (Myriad), and positive predictive values were 44.9 % (BRCAPRO) and 43.4 % (Myriad). Both BRCAPRO and Myriad II underestimated the risk of BRCA1/2 mutation in Koreans. Our findings suggest that these models are less sensitive in Korean women, and therefore a new BRCA mutation prediction model based on Korean data is needed for proper genetic counseling.

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Acknowledgments

This study was supported by a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea (1020350).

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Authors and Affiliations

  1. Department of Surgery, Seoul National University Bundang Hospital, 300 Gumidong, Bundanggu, Seongnamsi, Gyeonggido, 463-707, Korea

    Eunyoung Kang & Sung-Won Kim

  2. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea

    Sue K. Park & Jae Jeong Yang

  3. Department of Biomedical Science, Seoul National University Graduate School, Seoul, Korea

    Sue K. Park

  4. Cancer Research Institute, Seoul National University, Seoul, Korea

    Sue K. Park

  5. National Cancer Control Institute, National Cancer Center, Goyang, Korea

    Boyoung Park

  6. Department of Surgery, Soonchunhyang University Hospital, Seoul, Korea

    Min Hyuk Lee

  7. Department of Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea

    Jong Won Lee

  8. Department of Surgery, St. Vincent’s Hospital, The Catholic University of Korea, Suwon, Korea

    Young Jin Suh

  9. Department of Surgery, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea

    Jeong Eon Lee

  10. Department of Surgery, Korea Institute of Radiological and Medical Science, Korea Cancer Center Hospital, Seoul, Korea

    Hyun-Ah Kim

  11. Department of Surgery, Incheon St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Incheon, Korea

    Se Jeong Oh

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  1. Eunyoung Kang
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Correspondence to Sung-Won Kim.

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Kang, E., Park, S.K., Yang, J.J. et al. Accuracy of BRCA1/2 mutation prediction models in Korean breast cancer patients. Breast Cancer Res Treat 134, 1189–1197 (2012). https://doi.org/10.1007/s10549-012-2022-8

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