Abstract P4-09-13: A prognostic predictive model based on the correlation of standard clinicopathologic characteristics with oncotype Dx 21-gene recurrence score for node-negative and ER positive breast cancer
Authors: Mankbadi MR , Luo Y , Yasin M , Ben Khallouq B , Moroose R 
Published: February 2018

BACKGROUND: The Oncotype Dx Breast Cancer Assay (21-gene recurrence assay) is a prognostic tool that produces a recurrence score, which estimates the probability of distant recurrence within 10 years, given 5 years of adjuvant endocrine therapy as well as predicts benefit from adjuvant chemotherapy. The primary objective of this study was to explore if standard clinicopathologic variables independently correlate to the recurrence score. As a secondary objective, we explored if a model based on the clinicopathologic variables can accurately predict recurrence score.

METHODS: We conducted a retrospective chart review of 507 patients with node-negative, estrogen receptor (ER) positive breast cancer from the UF Health Cancer Center at Orlando Health. Of the 507 patients, 84 did not meet inclusion criteria (n = 423). The following factors were correlated with recurrence score (RS): age, tumor size, ER, PR, ki67, HER2 (IHC), HER2 (FISH), and tumor grade. Although the RS is a continuous variable, scores are also used to categorize patients into three risk groups: low (RS&lt;18), intermediate (18≤RS&lt;31), and high (RS≥31). This study evaluated variation of the HER2 levels within this subset of HER2 negative patients.

RESULTS: In univariate analysis, there were no significant correlations between age, ER, tumor size, Ki67 and RS. There were statistically significant correlations between PR (r=-.42, p&lt;.001), HER2 (IHC) (r=.097, p&lt;.05), HER2 (FISH) (r=0.40, p&lt;.001), and tumor grade (r=0.37, p&lt;.001) and RS. As a second step, we used these results and clinical expertise to guide a predictive model. As expected, independently, PR and tumor grade were significant predictors of RS (βs= -.096, .37, respectively; p&lt;.05). However, HER2 (IHC) was not, β=.097, p = .054. As a final step, three pathologic factors (PR, HER2 by IHC, and tumor grade) were used to predict recurrence score. In the multivariate analysis, we found a statistically significant model, (R = 0.54, RAdj = .30; F (3, 399) = 57.17, p &lt; .001), where, PR (β= -.096), HER2 (IHC) (β= 2.007), and tumor grade (β= 4.778). Concordance with the 21-gene assay was as follows: 76.0%, 54.5%, and 66.7% for low, intermediate, and high-risk groups, respectively. As clinical guidelines are not firmly established for the use of chemotherapy in the intermediate risk group it is also valuable to estimate the two-step discordance, an estimated RS that is high, when the 21-Gene recurrence score is low and vice versa. The two-step discordance was 2.2% and 0.0% for the low and high risk groups, respectively.

CONCLUSION: The data presented here suggests that it may be possible to create a model based on standard clinicopathologic parameters to predict the 21-gene recurrence score in node-negative, ER positive breast cancer patients. In practice, a 21-gene recurrence score assay is not always possible. We present an option to identify patients whose risk category can be confidently determined from the standard clinicopathologic variables alone, thereby reducing medical cost. Admittedly, this model has not undergone validation nonetheless, the data suggest the potential for a novel; low-cost; high reach diagnostic tool.

Citation Format: Mankbadi MR, Luo Y, Yasin M, Ben Khallouq B, Moroose R. A prognostic predictive model based on the correlation of standard clinicopathologic characteristics with oncotype Dx 21-gene recurrence score for node-negative and ER positive breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-09-13.