Abstract P4-06-01: OncotypeDX testing does not appear to benefit patients with grade 1, progesterone receptor positive breast cancers: A TAILORx validated study
Authors: Lee Young , Mylander W. Charles , Martin Tasha , Rosman Martin , Sanders Thomas J , Sibia Udai S , Tafra Lorraine , Jackson Rubie S 
Published: March 2022

Background: We previously described a validated (AAMC) risk prediction model, based on pathology, which may eliminate the need for OncotypeDX testing in AAMC low-risk (grade 1, progesterone (PR) positive) tumors. Our previous study used the SEER database and examined breast cancer specific survival (BCSS) and overall survival (OS), but was limited by our inability to assess distant recurrence-free interval (DRFI) and invasive disease-free survival (IDFS) with the available data. The purpose of this study was to validate the AAMC model using the TAILORx database, specifically with regard to DRFI and IDFS. Methods: We retrospectively analyzed TAILORx trial data and categorized patients into groups based on the AAMC model (Table). AAMC low-risk were defined as tumors that were both grade 1 and PR positive, while high-risk tumors were grade 3 or estrogen (ER) negative/PR positive. Intermediate-risk were those not categorized as low- or high-risk. The AAMC model recommends against OncotypeDX testing in low-risk tumors, but recommends testing in intermediate- or high-risk tumors. Kaplan-Meier curves were used to examine DRFI and IDFS. Results: A total of 9143 patients with grade and ER/PR information were categorized into AAMC low-risk (24.6%), intermediate-risk (57.9%), and high-risk (17.5%) groups. In the AAMC low-risk cohort, 22.3% had Recurrence Score (RS) 0-10 and did not receive chemotherapy per the TAILORx protocol, while 75.3% had RS 11-25 and were randomized to chemotherapy versus no-chemotherapy, and 2.4% had RS &gt; 25 and received adjuvant chemotherapy. In these AAMC low-risk patients, DRFI did not differ for patients who received adjuvant chemotherapy versus those that did not (log-rank p=.96). Similarly, IDFS was comparable between the chemotherapy and no-chemotherapy groups (log-rank p=.66). Only 2.4% of AAMC low-risk patients were categorized as high-risk per OncotypeDX testing (RS &gt; 25). To account for the fact that all patients in this small group received chemotherapy per protocol, a sensitivity analysis was performed in which AAMC low-risk patients with RS &gt; 25 were re-classified into the no-chemotherapy group and assumed to have experienced recurrences at rates expected without chemotherapy. Under these assumptions, there still was no difference in DRFI (log-rank p=.16) between chemotherapy and no-chemotherapy groups. Conclusion: This study validates our previous recommendations that OncotypeDX testing may be omitted in early-stage breast cancers with grade 1 and PR positive tumors (AAMC low-risk), as adjuvant chemotherapy does not improve distant recurrence-free interval in this group of patients. Based on our recommendations, 1 in 4 TAILORx participants would not need OncotypeDX testing. This would result in substantial cost savings to the healthcare system.

Percent of TAILORx trial participants and treatment recommendations based on OncotypeDX testing versus AAMC model.ModelAAMC ModelLow-risk (n=2246, 24.6%)Intermediate-risk (n=5298, 57.9%)High-risk (n=1599, 17.5%)Treatment recommendation*No chemotherapy/No OncotypeDX testingProceed with OncotypeDX testProceed with OncotypeDX testOncotypeDX testing*RS 0 to 15No chemotherapy1240 (55.2%)2224 (42.0%)306 (19.1%)RS 16 to 20, age ≤50Chemotherapy and/or OFS/AI258 (11.5%)492 (9.3%)108 (6.8%)RS 21 to 25, age ≤50Chemotherapy and/or OFS/AI93 (4.1%)274 (5.2%)101 (6.3%)RS 16 to 25, age &gt;50No chemotherapy600 (26.7%)1719 (32.4%)450 (288.1%)RS &gt;25Chemotherapy55 (2.4%)589 (11.1%)634 (39.6%)Ovarian function suppression (OFS); Aromatase inhibitor (AI)*Based on TAILORx results

Citation Format: Young Lee, W. Charles Mylander, Tasha Martin, Martin Rosman, Thomas J Sanders, Udai S Sibia, Lorraine Tafra, Rubie S Jackson. OncotypeDX testing does not appear to benefit patients with grade 1, progesterone receptor positive breast cancers: A TAILORx validated study [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 P4-06-01.