P4-10-06: Evaluation of BRCAPro Risk Assessment Model in Patients with Ductal Carcinoma In Situ.

Abstract

Abstract Background: The BRCAPRo model is used to predict a patient's likelihood to possess a BRCA1 or BRCA2 gene mutation based upon personal and family history. Ductal carcinoma in situ (DCIS) is considered a non-invasive condition which can progress to an invasive breast cancer if left untreated. Currently, DCIS is not specifically accounted for in the BRCAPro model, thereby causing DCIS to be weighted in the same manner as an invasive breast cancer diagnosis. Historically, a diagnosis of DCIS has been entered as having developed into an invasive breast cancer ten years later. However, there are no standard guidelines of how DCIS should be entered. We sought to determine if there were any differences in how DCIS was treated in the BRCAPro model to predict the more effective method in calculating the BRCAPro. Methods: Women with pure DCIS, who were referred for genetic counseling and underwent genetic testing, were included in the study. The likelihood of carrying a BRCA mutation was calculated using the BRCAPRO model (Version 5.1). Patient characteristics which were entered into the BRCAPro model include: tumor markers (estrogen receptor-ER and progesterone receptor-PR), history of oophorectomy prior to diagnosis, family history of 1st and 2nd degree relatives with breast and ovarian cancer, race and Ashkenazi Jewish ancestry. Each patient's BRCAPro risk estimate was calculated and compared by entering DCIS at the presenting age of diagnosis and by adding 10 years to the age of diagnosis. Descriptive statistics and a student's t-test were used to compare BRCAPro estimates between the two groups. Results: Ninety-five patients with pure DCIS underwent genetic counseling and testing. The average age of DCIS diagnosis was 45 years (range 26–65). Of the 95 DCIS patients included in the study 21% (n=20) tested positive for a BRCA gene mutation (8 BRCA1 and 12 BRCA2), 77% (n=74) test negative and 0.01% (n=1) had a variant of uncertain significance. Overall, DCIS patients who tested positive for a BRCA mutation had a higher BRCAPro (40%) than patients who tested negative (12%) when presenting age of diagnosis was assessed. When 10 years was added, the BRCAPro estimate was still higher amongst BRCA positive patients (28%) than BRCA negative patients (8%). The mean BRCAPro probability when DCIS was entered at presenting age of diagnosis was 18% (0.1−95.4) versus 12% (0.1−89.9) when calculated 10 years later. Conclusion: In our cohort there was no significant difference in BRCAPro probability whether DCIS was entered at the presenting age of diagnosis or 10 years later (p=0.1). However, future studies are needed to determine the most effective method to incorporate DCIS into the BRCAPro model in order to determine those individuals who may or may not be at increase risk to possess a BRCA gene mutation. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-06.