Abstract P2-14-05: Sporadic breast cancer risk assessment in women without family history and biopsy using the OncoVue® polyfactorial model
Authors: ER Jupe, TW Pugh, NS Knowlton, DC DeFreese
Journal: Cancer Research (2013)

Abstract Background: The majority of breast cancer cases are considered to be sporadic and occur in women without a strong family history. Accurate estimation of a woman's risk of developing breast cancer is essential for guiding decisions regarding surveillance and prevention. The Breast Cancer Risk Assessment Tool (BCRAT) uses only clinical factors and has been shown to be of marginal value for individual risk counseling. Even though the BCRAT risks for women without a biopsy and no first degree relative with breast cancer are low, a significant fraction of cases occur in these women. OncoVue® is a logistic regression model developed from individual genetic and personal factor data from a large case-control study. In three independent validation populations, including a blinded validation, OncoVue has been shown to significantly outperform BCRAT. Here we compare OncoVue to the BCRAT in stratifying risk in women without a first degree relative with breast cancer that have never had a breast biopsy. Materials and Methods: Absolute risks for Caucasian participants ranging in age from 35 to 89 were analyzed for a case-control study conducted in six distinct geographic regions of the United States. This analysis focused on participants that had never had a biopsy and reported no first degree relatives with breast cancer (cases prior to diagnosis/controls at time of enrollment). DNAs from a total of 2729 women (842 cases and 1887 controls) were genotyped for 22 SNP variants and genotype information was combined with clinical risk information to calculate 5-year and lifetime risks. Clinical factor information alone was used to calculate BCRAT risk scores for comparison to OncoVue. Results: The 5-year risks for OncoVue ranged from 0.10 to 5.0% (50-fold) compared to 0.20 to 3.0% (15-fold) for BCRAT risks. OncoVue lifetime risks ranged from 2.4 to 25.0% (11-fold) compared to 4 to 16% (4-fold) for BCRAT risks. The OncoVue model 5-year risk placed 11% of this sub-population of controls at ≥ 2.0% risk compared to the BCRAT which placed only 3.5% at this risk. The BCRAT did not place anyone at a lifetime risk over 16% while OncoVue placed 10% of this sub-population of controls above 16%. The Odds Ratio (OR) was determined at increasing model risk output levels. Over comparable ranges, OncoVue 5-year risks exhibited statistically significant ORs while BCRAT ORs did not reach significance. OncoVue associations for lifetime risk reach high levels. For example, an OR of 5.0 (p = 0.03) was observed at a risk level ≥ 23%. Conclusion: The OncoVue model stratifies risk over a much wider range than the BCRAT in this group of women at low risk by traditional methods. In the 5-year risk frame OncoVue exhibited improved performance in estimating individual risk compared to the BCRAT. Due to the lack of any elevated lifetime risks generated by the BCRAT, a direct comparison of lifetime risks for OncoVue to the BCRAT was not possible. The OncoVue model which uses both genetics and clinical factors significantly improves individualized breast cancer risk estimation. These results demonstrate the importance of the genetic component of the OncoVue model in accurately estimating individual risk of sporadic breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-14-05.