31P - Multigene sequencing for the genetic diagnostics of patients with early-onset or familial breast cancer

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Breast Cancer, Early Stage
Familial Cancer
Imaging, Diagnosis and Staging
Personalised Medicine
Translational Research
Presenter Po-Han Lin
Citation Annals of Oncology (2015) 26 (suppl_3): 10-14. 10.1093/annonc/mdv116
Authors P. Lin1, W. Kuo2, C. Lin3, Y. Lu3, Y. Ni4, C. Huang2
  • 1Medical Genetics, National Taiwan University Hospital, 100 - Taipei/TW
  • 2Surgery, National Taiwan University Hospital, Taipei/TW
  • 3Medical Oncology, National Taiwan University Hospital, Taipei/TW
  • 4Medical Genetics And Pediatrics, National Taiwan University Hospital, Taipei/TW



Purpose: Epidemiologic studies show that the median age of breast cancer patients is younger in Taiwan than in western populations, and breast cancer patients in Taiwan carry a greater risk and a shorter interval to develop contralateral breast cancer. These two characteristics indicate genetic predisposing factors. In this study, we used a customized multigene sequencing panel to investigate the genetic impact for patients with early-onset or a significant family history in Taiwan.

Methods: We recruited 106 patients who met one of the following criteria: (1) early-onset breast cancer (age <35 years) or bilateral breast cancer, (2) breast cancer onset before age 50 years together with at least one first or second-degree relative having breast cancer or ovarian cancer, or (3) breast cancer after age 50 years, but with three relatives having breast cancer or ovarian cancer. Germline genomic DNA was extracted form peripheral blood mononuclear cells for next-generation sequencing.

Results: A total of 24 patients (22.6%) were found with germline pathogenic mutations among the known cancer susceptibility genes, including one ATM, eight BRCA1, 10 BRCA2, one BRIP1, one FANCI, one MSH2, one RAD50 and one TP53. The mutation prevalence were 22.9% (age <35 years), 22.0% (35-50 years) and 25.0% (after age 50 years), respectively. When assessed by the molecular subtype of breast cancer, the mutation prevalence was 17.6% in patients with hormone receptor (HR, +) Her2(-) breast cancer, 16.7% in HR(+)Her2(+) breast cancer, no mutation detected in only Her2(+) and 60.0% in triple-negative breast cancer (TNBC) (p = 0.003). Seven of eight BRCA1 mutations and 2 of 10 BRCA2 mutations were found in patients with TNBC; other BRCA1 and BRCA2 mutations were in patients with HR(+)Her2(-). ATM, RAD50 and TP53 mutation were noted in patients with HR(+)Her2(+), BRIP1 and MSH2 mutation in HR(+)Her2(-) and FANCI mutation in TNBC.

Conclusion: Our findings demonstrate 22.6% of overall mutation rate in patients with familial or early-onset breast cancer. The mutation rate of TNBC is significantly higher than HR(+) and Her2(+) breast cancer. This information helps us to perform cancer risk assessment, improving genetic counseling and further cancer treatment.

Disclosure: All authors have declared no conflicts of interest.