Prevalence of BRCA1 and BRCA2 mutations in women diagnosed with ductal carcinoma in situ.

1512 Background: The frequency of a BRCA mutation among women with ductal carcinoma in situ (DCIS) has not been well described. Consequently, patients with DCIS were not historically considered ideal candidates for genetic testing even in the presence of a family history of breast and ovarian cancer. Therefore, we examined the prevalence of BRCA1/2 mutations in women diagnosed with DCIS. METHODS Patients with DCIS, who were referred for genetic counseling and underwent genetic testing, were included in the study. Patient characteristics were obtained from a prospectively maintained research database. This study was approved by institutional review board. The likelihood of carrying a BRCA mutation was calculated using the BRCAPRO model (Version 5.1). Chi-square analysis was used to determine the difference among mutations carriers vs. non-carriers with DCIS. RESULTS One hundred and twenty nine patients diagnosed with DCIS underwent genetic testing for BRCA mutations. Twenty-eight percent (37/129) of DCIS patients tested positive for a deleterious BRCA mutation (15 BRCA1, and 22 BRCA2). In addition, 6 were found to have a variant of uncertain significance (VUS). The average age of diagnosis was 46.2 yrs (30-69) in BRCA positive patients and 43.5 yrs (26-65) in BRCA negative patients (p =0.177). Patients who tested positive for the BRCA mutations had significantly more family history of breast and ovarian cancer (p=0.021, p=0.006 (respectively) than those who tested negative; as reflected by the BRCAPro calculation (p ≤0.0001). Fifty seven percent of BRCA positive patients had one breast removed for prophylactic reasons while only 28% BRCA negative patients did (p=0.004). This effect was significantly stronger for patients ≤40 (p=0.007). CONCLUSIONS Patients with DCIS and a family history of breast and/or ovarian cancer have a high rate of BRCA positivity regardless of age. These findings suggest that patients with DCIS are appropriate candidates for genetic testing in the presence of family history and regardless of age even if they do not have invasive cancer.