Abstract PD7-03: A model using grade and hormone receptor staining defines groups at low vs. high risk for distant metastasis: Comparison to the 21-gene recurrence score
Authors: Mylander C , Jackson RS , Rosman M , Fujii T , Le Du F , Raghavendra A , Sinha A , Ueno NT , Tafra L 
Published: March 2017

Background: The 21-gene recurrence score (RS) combines breast cancer (BC) expression of multiple genes into a single number which is prognostic for BC recurrence. We previously showed that a model using standard pathology data (AAMC Risk Groups) has substantial overlap with RS Risk Groups. The present study compared the recurrence rate of AAMC Risk Groups to that of RS-based Risk Groups as defined by the TAILORx trial and OncotypeDX (ODX) assay.

Methods: From a prospective registry of BC treated at MD Anderson Cancer Center (2/2005 – 5/2015), we selected cases tested with ODX. Cases were excluded for: other cancer in the past 5 years, T4 stage, node positivity, missing grade, missing ER%, ER&PR&lt;1% or HER2 positivity. Three methods were used to categorize distant metastatic risk: ODX and TAILORx Risk Groups were defined using RS, and AAMC Risk Groups were defined using grade and ER/PR level (Tables). For each method, the proportion of patients experiencing metastasis was calculated within Risk Groups.

Results: 1296 cases were included, with a mean follow-up of 3.5 years (25% had ≥ 4.9 years of follow-up). 82 cases (6.3%, 95% CI 5.1 – 7.8%) experienced distant metastasis, with a mean time-to-metastasis of 2.7 years. The proportion of patients experiencing distant metastasis was similar between the AAMC Low Risk Group (1.5%) and the TAILORx (3.2%) and ODX (2.4%) Low Risk Groups. The AAMC Low Risk Group was less than half the size of the ODX Low Risk Group. Of the 5 recurrences in the AAMC Low Risk Group, 1 was ODX Low Risk and 4 were ODX Intermediate Risk; 2 had 1% PR staining. Of the 17 recurrences in the ODX Low Risk Group, 1 was AAMC Low Risk and 5 (all grade 3) were AAMC High Risk; 3 had PR staining &lt; 10%. The proportion of patients experiencing distant metastasis was similar between the AAMC High Risk Group (17.4%) and the TAILORx (16.4%) and ODX (18.2%) High Risk Groups. The number of patients in the AAMC High Risk Group was greater than the ODX High Risk Group.

Table 1: Distant Metastasis in Low Risk GroupsAAMC Definition (n=329)TAILORx Definition (n=250)OncotypeDX Definition (n=704)Low Risk DefinitionGrade 1 & PR ≥1%RS &lt; 11RS &lt;18% with Distant Metastasis1.5% (95% CI 0.6–3.7%; n=5)3.2% (95% CI 1.5-6.4%, n=8)2.4% (95% CI 1.5-3.9%, n=17)% in Common with AAMC Low Risk Group100% (329/329)31.7% (80/250)33.3% (235/704)

Table 2: Distant Metastasis in High Risk GroupsAAMC Definition (n=235)TAILORx Definition (n=238)OncotypeDX Definition (n=148)High Risk DefinitionGrade 3 or ER &lt;20%RS &gt; 25RS &gt; 30% with Distant Metastasis17.4% (95% CI 12.9-23.0%, n=41)16.4% (95% CI 12.0-21.8%, n=39)18.2% (95% CI 12.6– 25.6%, n=27)% in Common with AAMC High Risk Group100% (235/235)56.7% (135/238)70.3% (104/148)

Conclusions: AAMC Low and High Risk Groups were prognostic of the likelihood of distant metastasis, and performed similarly to TAILORx and ODX Low and High Risk Groups. If RS were omitted for AAMC Low and High Risk cases, 44% [(329+235)/1296] of cases in the present cohort could have been spared ODX testing. The AAMC Risk Groups, using standard pathology data, can reliably identify a large number of patients unlikely to benefit from ODX testing and thus provide substantial cost savings.

Citation Format: Mylander C, Jackson RS, Rosman M, Fujii T, Le Du F, Raghavendra A, Sinha A, Ueno NT, Tafra L. A model using grade and hormone receptor staining defines groups at low vs. high risk for distant metastasis: Comparison to the 21-gene recurrence score [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr PD7-03.