Frequency Of BRCA1 Germline Mutations Research Articles

Prevalence of BRCA1 mutations and responses to neoadjuvant chemotherapy among BRCA1 carriers and non-carriers with triple-negative breast cancer

The frequency of BRCA1 germline mutations among Chinese women with triple-negative breast cancer is unclear, and the association between BRCA1 mutations and the response to neoadjuvant chemotherapy in women with triple-negative breast cancer has not been determined. Nine hundred and fifty-six triple-negative breast cancer patients were treated at our institute between 2003 and 2012; we tested the BRCA1/2 mutations for 956 patients and 953 patients in this cohort, respectively. Among the 956 patients, 652 patients received neoadjuvant chemotherapy. In this cohort, 7.1% (68/956) and 2.3% (22/953) of patients carried a BRCA1 or BRCA2 mutation, respectively. The BRCA1/2 mutation rates were 10.5% and 3.0% among the patients who were diagnosed at or before the age of 50 in this cohort, respectively. The pCR (pathologic complete response) rate was 31.6% in the 652 patients who received neoadjuvant chemotherapy. BRCA1 carriers had a significantly higher pCR rate than non-carriers (BRCA1 carriers versus non-carriers, 53.8% versus 29.7%, P < 0.001). Among women treated with anthracycline with or without taxane regimens, the pCR rate was 57.1% for BRCA1 carriers, 29.0% for non-carriers (P < 0.001); among women treated with taxane regimens, the pCR rate was 40.0% for BRCA1 carriers, 32.9% for non-carriers (P = 0.73). At a median follow-up of 43 months, the recurrence-free survival was similar between BRCA1 carriers and non-carriers among the 947 patients of this study (adjusted hazard ratio = 0.92; 95% confidence interval: 0.45-1.90; P = 0.82). Chinese women with triple-negative breast cancer who are diagnosed at or before age of 50 are candidates for BRCA1 genetic testing. Among triple-negative breast cancer patients, BRCA1 carriers are more likely to respond to neoadjuvant anthracycline-based regimens than are non-carriers.

Evaluation of BRCA2 in the genetic susceptibility of familial esophageal cancer

Previous studies of esophageal squamous cell carcinoma (ESCC) have shown a high frequency of allelic loss on chromosome 13q, infrequent somatic mutations in BRCA2, and a suggested association between a positive family history (FH+) of upper gastrointestinal cancer and germline BRCA2 mutations. In all, 70 ESCC patients (44 FH+ and 26 FH-) were examined by direct full sequencing of germline DNA for BRCA2 mutations. In addition, 28 family members of three of these patients and 232 unrelated healthy blood bank donor controls were examined for the mutations identified in the 70 ESCC patients. Five BRCA2 germline mutations, including three not previously reported (N1600del, A2054P, and V2109I), were identified in six of 44 FH+ patients, but none of 26 FH- patients (14 vs 0%, P=0.078), consistent with our previous findings (3/34 or 9% FH+ vs 0/22 or 0% FH-, P=0.27). The cumulative frequency of BRCA2 germline mutations in ESCC patients in this and our previous study combined is 12%, with all mutations found in FH+ as opposed to FH- cases (9/78 or 12% FH+ vs 0/48 or 0% FH-, P=0.013). We conclude that germline mutations in BRCA2 in ESCC patients from this high-risk area of China are more frequent in FH+ than FH- cases, suggesting that BRCA2 may play a role in genetic susceptibility to familial ESCC.

BRCA2 germline mutations in Swedish breast cancer families.

Mutations in the breast cancer susceptibility gene (BRCA2) are believed to be responsible for a significant fraction of hereditary breast cancer. To determine the BRCA2 mutation spectrum in a subset of Swedish breast cancer families, 162 families were screened for germline mutations in this gene. A combination of RT-PCR, PTT and direct DNA sequencing was used. Two mutations and one previously reported polymorphic variant resulting in a truncated protein were identified. Our data suggest that only a small proportion of Swedish breast cancer families is attributable to BRCA2 germline mutations. This result, in combination with the low frequency of BRCA1 germline mutations identified in our previous study, suggests additional high penetrant as well as low penetrant breast cancer susceptibility genes are involved in familial breast cancer.

Low frequency of BRCA1 germline mutations in 45 German breast/ovarian cancer families.

In this study we investigated 45 German breast/ovarian cancer families for germline mutations in the BRCA1 gene. We identified four germline mutations in three breast cancer families and in one...