Characteristics of double heterozygosity for BRCA1 and BRCA2 germline mutations in Korean breast cancer patients

To investigate clinical, pathological, and familial characteristics of Korean patients with double heterozygosity for BRCA1 and BRCA2 mutations, six breast tumors of five patients who carried deleterious mutations in both of the genes were included. Medical records of the patients were reviewed and genetic testing by direct sequencing was undertaken to detect mutations in BRCA1 and BRCA2. Seven frameshift and three nonsense mutations were identified, and four mutations are novel in the Breast Cancer Information Core. There were no Ashkenazi founder mutations detected. The mean age at diagnosis for breast cancer was 33 years. All six tumors were infiltrating ductal carcinoma and poorly differentiated. Pathologic stage was I or II, and immunohistochemistry showed negative immunoreactivity for estrogen receptor and Her-2/neu in all tumors. Positive immunoreactivity for progesterone receptor was found only in one tumor. Three patients had familial history of breast, ovarian or other cancers. One patient who was diagnosed for breast cancer at the age of 26 had two maternal family members of metachronous bilateral breast cancer. Another patient who experienced metachronous bilateral breast cancer had maternal history of ovarian and esophageal cancer. In summary, Korean patients with double heterozygosity for BRCA1 and BRCA2 were young at diagnosis of breast cancer. Tumors were early stage, high grade, and almost triple-negative phenotype. All familial history of breast, ovary or other cancer was maternal. Close surveillance and accurate risk assessment should be provided for the patients with mutations in the both of the genes.