Abstract P1-10-02: Recurrence score testing does not appear to benefit patients with grade I PR positive breast cancers: An opportunity to eliminate over-treatment and decrease testing costs
Authors: Jackson Rubie Sue , Sanders Thomas , Rosman Martin , Mylander Charles , Tafra Lorraine 
Published: March 2020

Abstract
Background: We previously showed that a risk prediction model (AAMC model) based on standard pathology data can eliminate the need for Recurrence Score (RS) testing in a large proportion of cases. There is concern about whether cases with discordant risk predictions by AAMC vs. RS methodology would be under- or over-treated if RS testing were omitted.
Methods: This is a retrospective analysis of ER +, T1b-T2 breast cancers with an available OnoctypeDX score in the SEER database (2004-2015). Cases with documented HER2 positivity, node positivity (≥Nmi), or metastatic disease were excluded. The AAMC low-risk group was defined as tumors that were grade 1 and PR not recorded as negative. The AAMC high-risk group was defined as grade 3. Low RS was defined as RS &lt;16 and age ≤50, or RS ≤ 25 and age &gt;50. High RS was defined as &gt; 25. Within discordant groups (AAMC low/RS high or AAMC high/RS low), Kaplan-Meier methods were used to assess 10-year breast cancer specific survival (BCSS), comparing patients who received chemotherapy to those who did not.
Results: 72,761 cases were analyzed. Of these, 615 (0.8%) were AAMC low-risk/RS high-risk discordant, and 5,785 (8.0%) were AAMC high-risk/RS low-risk discordant (Table 1). For AAMC low/RS high discordant cases, 10-year BCSS was &gt;98% for cases not receiving chemotherapy, with no difference by treatment group (p=0.12; Table 2). For AAMC high/RS low discordant cases, 10-year BCSS was 93.2% in patients who received chemotherapy and 96.8% in patients who did not receive chemotherapy, and did not differ by treatment group (p=0.09; Table 2). Overall survival also did not differ by treatment group, for either discordant category (Table 2).
Conclusions: The very high 10-year BCSS regardless of treatment (chemotherapy vs. no chemotherapy) in the AAMC low/RS high group suggests that RS testing may not benefit patients with grade 1, PR positive tumors. In this population-based study, 27% (19,571/72,761) of Oncotype-tested patients were AAMC low-risk and received RS testing without apparent benefit. In fact, patients with grade 1 tumors without negative PR who received chemotherapy due to high RS may have been harmed, since we cannot demonstrate benefit from chemotherapy in this subgroup. However, our data suggest that patients with grade 3 tumors do benefit from RS testing, since administration of chemotherapy did not appear to benefit patients with grade 3 tumors and low RS. In a resource-constrained setting, consideration should be given to omitting Oncotype testing in tumors that are both grade 1 and PR positive. A limitation of this study is lack of recurrence as an endpoint in the SEER database; 10 year follow up may be insufficient to detect a difference in BCSS for ER positive tumors. However, using the SEER database allowed for analysis of a large number of cases. Since AAMC-RS discordant cases are uncommon, it would be difficult to achieve the statistical power of the present analysis in a prospective dataset such as the TAILORx trial data.
Table 1. Cohort classified by Recurrence Score and AAMC Risk GroupsAAMC Low RiskAAMC Indeterminate RiskAAMC High RiskTotalRS Low (RS &lt;16 and age ≤50 y; RS &lt;25 and age &gt;50 y)17,04431,9485,78554,777RS Intermediate (RS 16-25 and age ≤50 y)1,9124,3971,1617,470RS High (RS &gt;25)6154,9314,96810,514Total19,57141,27611,91472,761
Table 2. 10-year breast cancer-specific survival (first) and overall survival (second)ChemotherapyNo chemotherapyp-valueAAMC low-risk/RS high-risk93.1%//91.6%98.8%//92.3%0.12//0.43AAMC high-risk/RS low-risk93.2%//88.8%96.8%//90.3%0.09//0.63
Citation Format: Rubie Sue Jackson, Thomas Sanders, Martin Rosman, Charles Mylander, Lorraine Tafra. Recurrence score testing does not appear to benefit patients with grade I PR positive breast cancers: An opportunity to eliminate over-treatment and decrease testing costs [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-02.