Abstract P3-09-05: Getting the most out of the 21-gene recurrence score assay: Increasing actionable results with a combined pathologic-genomic model
Authors: Mylander C , Rosman M , Gage M , Fujii T , Le Du F , Raghavendra A , Sinha A , Espinosa Fernandez JR , James A , Ueno N , Tafra L , Jackson R 
Published: February 2018

Introduction: The 21-gene recurrence score (RS) assay categorizes hormone receptor positive, node negative breast cancers (BC) into 3 risk groups for recurrence. We previously showed that the AAMC Model, using only standard pathology data, accurately does the same. This study compares the recurrence rate of the AAMC Model's risk groups to RS-based risk groups. A 2-step approach then is used, in which the AAMC model is applied first, and the RS assay is used only for AAMC intermediate risk cases. AAMC intermediate cases were reclassified by RS into low or high risk groups.

Methods: From a prospective registry of newly diagnosed BC, we selected invasive, hormone receptor positive, HER2 negative, lymph node negative cases from 2005 to 2015 tested with RS assay. Five-year Kaplan-Meier distant recurrence rates were calculated for each risk category.

Results: 1268 cases were included. Five-year recurrence rates were similar between the AAMC Model's low risk group and RS&lt;18 low risk group, as well as between the AAMC Model's high risk group and the RS&gt;30 high risk group. Applying the RS assay to the 715 cases in the AAMC Model's intermediate group resulted in re-classifying 417 (58%) as low risk and 41 (6%) as high risk. Using RS alone, 33% of cases were intermediate risk (n=424), whereas in the 2-step approach 20% were intermediate risk (n=257). For the 2-step approach, the 5-year distant recurrence rate was 3.3% for the low risk group (n=740) and 24.4% for the high risk group (n=271).

Conclusions: Five-year recurrence rates in the AAMC Model's low and high risk groups were similar to those in RS-based risk groups. The 2-step approach, with RS used only for AAMC intermediate cases, resulted in larger low and high risk groups with equivalent prognostic accuracy, compared to use of the RS assay alone. The 2-step approach reliably identifies a large number of patients unlikely to benefit from 21 gene assay and provides substantial cost savings.

Kaplan-Meier Calculated 5-year Distant Recurrences Rates for 4 Models: 1268 Patients Oncotype DXTAILORxAAMC Model2 Step Model with OncotypeDX for AAMC IntermediatesLow RiskRS &lt; 18 (n=703)RS &lt; 11 (n=250)Grade 1 and PR ≥ 1% (n=323)AAMC Low or AAMC intermediate/RS &lt;18 (n=740) 3.4% (95% CI 1.6 – 5.1%, nf=17)4.0% (95% CI 0.8 – 7.2%, nf=8)2.7% (95% CI 0.0 – 5.4%, nf=5)3.3% (95% CI 1.4 – 5.2%, nf=16)Intermediate RiskRS 18 - 30 (n=424)RS 11 - 25 (n=787)Not meeting AAMC definition for low or high risk (n=715)AAMC Intermediate and RS 18-30 (n=257) 15.2% (95% CI 10.3 – 20.1%, nf=38)7.3% (95% CI 4.7 – 9.9%, nf=35)8.4% (95% CI 5.4 – 11.3%, nf=36)12.0% (95% CI 5.8 – 18.1%, nf=15)High RiskRS &gt; 30 (n=141)RS &gt; 25 (n=231)Grade 3 or ER &lt; 20% (n=230)AAMC High or AAMC intermediate/RS &gt; 30 (n=271) 23.0% (95% CI 14.7 – 31.3%, nf=27)22.9% (95% CI 15.9 – 29.9%, nf=39)22.8% (95% CI 16.1 – 29.5%, nf=41)24.4% (95% CI 18.0 – 30.7%, nf=51)RS= Recurrence Score, nf=number of recurrences, CI = confidence interval.

Citation Format: Mylander C, Rosman M, Gage M, Fujii T, Le Du F, Raghavendra A, Sinha A, Espinosa Fernandez JR, James A, Ueno N, Tafra L, Jackson R. Getting the most out of the 21-gene recurrence score assay: Increasing actionable results with a combined pathologic-genomic model [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 P3-09-05.