Abstract PD9-01: Expanding downstaging criteria in AJCC pathologic prognostic staging using OncotypeDx Recurrence Score® assay in T1-2N0 hormone-receptor positive patients enrolled in the TAILORx trial
Authors: Kantor Olga , Burstein Harold J , King Tari , Shak Steven , Russell Christy , Giuliano Armando E , Hortobagyi Gabriel N , Winer Eric P , Korde Larissa A , Sparano Joseph A , Mittendorf Elizabeth A 
Published: March 2022

Background: The AJCC 8th edition pathologic prognostic staging (PPS) system, which incorporates both anatomic and biologic factors, was developed using data from patients captured in the National Cancer Database diagnosed 2010-2012 in whom complete anatomic (T, N and M category) as well as biologic data (grade, ER, PR, HER2) were available. The clinical endpoint was 3-year overall survival. In addition, the use of genomic assays was incorporated based on the initial report from the TAILORx trial, with patients with T1-2N0 hormone-receptor positive, HER2 negative (HR+,HER2-) breast cancer and an Oncotype DX Recurrence Score® (RS) result &lt;11 being staged as PPS IA. Given availability of long-term prospective followup data from TAILORx, we undertook this study to examine if the RS criteria for downstaging to PPS IA can be expanded using the patients enrolled on this trial. Methods: TAILORx assigned T1-2N0 HR+HER2- breast cancer patients with RS &lt;11 to endocrine therapy (ET) alone and RS &gt;25 to chemotherapy followed by ET (CET). Those with RS 11-25 were randomized to ET or CET. 10,273 patients were enrolled. Patients with incomplete HR status or grade and those with T3 disease were excluded for this analysis. Recurrence-free survival (RFS) in patients with RS &lt;11 were compared between patients that did and did not fall into current AJCC PPS IA category using the Kaplan-Meier method. Results: 9,535 patients were included for analysis. The majority were &gt; 50 years old (n=6893, 72.3%), had T1 tumors (n=6561, 68.8%), grade 2 disease (n=5291, 55.5%), and underwent lumpectomy (n=6855, 71.9%). RS breakdown was &lt;11 in 1539 (16.1%), 11-17 in 3423 (35.9%), 18-25 in 3088 (32.4%) and &gt;25 in 1485 (15.6%). 8,698 (91.2%) patients were AJCC PPS IA (including all T1N0 patients regardless of RS), and 837 (8.8%) were not PPS IA. Median follow-up time was 95 months. PPS IA patients had 8-yr RFS of 94.2% which was statistically similar to patients with RS 11-17 that were not PPS IA (91.7%, p=0.07) and better than patients with RS &gt;18 that were not PPS IA (85.4% for RS 18-25, 76.0% for RS &gt;25, p&lt;0.01). For patients with a RS 11-17 that were not PPS IA receiving ET alone, 8-yr RFS was 93.3% which was statistically similar to PPS IA patients receiving ET alone (94.9%, p=0.24). There was no RFS benefit with CET for patients with RS 11-17 not PPS IA (Table). Conclusions: Patients with T1-2N0 HR+HER2- breast cancer and RS&lt;18 have similar RFS to patients staged as PPS IA by the current AJCC staging system, regardless of treatment, suggesting that consideration could be given to expanding the criteria for pathologic prognostic stage IA to include RS&lt;18.

Comparison of RFS in patients with Stage IA and not Stage IA by AJCC PPS, n=9535Stage IANot stage IA, RS 11-17Not stage IA, RS 18-25Not stage IA, RS &gt;25All Patients, n=9535n=8698n=169n=269n=3998yr RFS % (95% CI)94.2 (93.6-94.8)91.7 (87.0-96.4)85.4 (80.3-90.5)76.0 (69.1-82.9)P-value*Ref0.07&lt;0.01&lt;0.01ET, n=5370n=5123n=88n=135n=248yr RFS % (95% CI)94.9 (94.1-95.7)93.3 (87.6-99.9)85.1 (77.8-92.4)58.3 (77.8-92.4)P-value*Ref0.24&lt;0.01&lt;0.01CET, n=4165n=3575n=81n=134n=3758yr RFS % (95% CI)93.2 (92.2-94.2)90.0 (82.4-97.6)85.8 (78.7-92.9)76.9 (69.8-84.0)P-value*Ref0.019&lt;0.01&lt;0.01ET endocrine therapy; CET chemoendocrine therapy*compared to T1-2N0 patients with PPS IA

Citation Format: Olga Kantor, Harold J Burstein, Tari King, Steven Shak, Christy Russell, Armando E Giuliano, Gabriel N Hortobagyi, Eric P Winer, Larissa A Korde, Joseph A Sparano, Elizabeth A Mittendorf. Expanding downstaging criteria in AJCC pathologic prognostic staging using OncotypeDx Recurrence Score® assay in T1-2N0 hormone-receptor positive patients enrolled in the TAILORx trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD9-01.