Predictive factors for BRCA1/BRCA2 mutations in women with ductal carcinoma in situ

• Published in: Cancer Vol. 118; no. 6; pp. 1515 - 1522
• Main Authors: Bayraktar, Soley, Elsayegh, Nisreen, Gutierrez Barrera, Angelica M., Lin, Heather, Kuerer, Henry, Tasbas, Tunc, Muse, Kimberly I., Ready, Kaylene, Litton, Jennifer, Meric‐Bernstam, Funda, Hortobagyi, Gabriel N., Albarracin, Constance T., Arun, Banu
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-03-2012; Wiley-Blackwell
• Subjects: Adult; Biological and medical sciences; BRCA 1/2 mutations; BRCAPRO; Breast Neoplasms - genetics; Breast Neoplasms - surgery; Carcinoma, Intraductal, Noninfiltrating - genetics; Carcinoma, Intraductal, Noninfiltrating - surgery; ductal carcinoma in situ; family history; Female; Genes, BRCA1; Genes, BRCA2; Humans; Logistic Models; Medical sciences; Middle Aged; Mutation; predictive factors; Predictive Value of Tests; Tumors; Human; Ductal carcinoma; Carcinoma in situ; BRCAPRO; BRCA 1/2 mutations; Malignant tumor; ductal carcinoma in situ; Family story; Cancerology; BRCA2 gene; family history; predictive factors; Adult; Female; Genetics; Mutation; Predictive factor; Woman; BRCA1 gene; Antecedent; Cancer; Tumor suppressor gene
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.26428

BACKGROUND:
It is unclear whether women with ductal carcinoma in situ (DCIS), like their counterparts with invasive breast cancer, warrant genetic risk assessment and testing on the basis of high‐risk variables. The authors of this report identified predictive factors for mutations in the breast cancer‐susceptibility genes BRCA1 and BRCA2 in women who were diagnosed with DCIS.
METHODS:
One hundred eighteen women with DCIS who were referred for genetic counseling and underwent genetic testing for BRCA1/BRCA2 mutations between 2003 and 2010 were included in the study. Logistic regression models were fit to determine the associations between potential predictive factors and BRCA status.
RESULTS:
Of 118 high‐risk women with DCIS, 27% (n = 32) tested positive for BRCA1/BRCA2 mutations. Of those, 10% (n = 12) and 17% (n = 20) had BRCA1 and BRCA2 mutations, respectively. Age, race, and tumor characteristics did not differ between BRCA noncarriers and carriers. In a multivariate logistic model, ≥2 relatives with ovarian cancer (OC) (odds ratio [OR], 8.81; 95% confidence interval [CI], 1.38‐56.29; P = .034), and a score ≥10% according to the BRCAPRO mathematical model for calculating the probability that a particular family member carries a germline BRCA mutation (OR, 6.37; 95% CI, 2.23‐18.22; P = .0005) remained as independent significant predictors for a BRCA mutation. Fifty‐seven percent of mutation carriers but only 25% of noncarriers underwent prophylactic mastectomy(P = .0037). This difference remained significant for patients aged ≤40 years (P = .025).
CONCLUSIONS:
Women who had DCIS and a family history of OC or who had BRCAPRO scores ≥10% had a high rate of BRCA positivity regardless of age at diagnosis. These findings suggest that high‐risk patients with DCIS are appropriate candidates for genetic testing for BRCA mutations in the presence of predictive factors even if they do not have invasive breast cancer. Cancer 2011;. © 2011 American Cancer Society.
Of 118 high‐risk women with ductal carcinoma in situ (DCIS), 27% (n = 32) test positive for breast cancer‐susceptibility gene (BRCA1/BRCA2) mutations. Women who have DCIS and a family history of at least 2 relatives affected with ovarian cancer or who have scores ≥10% according to BRCAPRO (a mathematical model for calculating the probability that a particular family member carries a germline BRCA mutation) have high rates of BRCA positivity regardless of their age at diagnosis.