Treatment recommendations in ER plus patients <= 50 years: Comparison of the 21-gene assay and 70-gene signature in the PROMIS study

Background: The PROMIS trial (NCT01617954) previously evaluated how a definitive result from the MammaPrint 70-gene signature (70-GS) can impact treatment recommendations for patients with an intermediate range recurrence score (RS 18-30) from the 21-gene assay (21-GA, Oncotype DX). Since publication of this study, TAILORx results published in 2018 (and further explored in June 2019) suggested an interaction between the 21-GA, patient age (≤50 yrs), and clinical risk. Initially, chemotherapy (CT) was recommended for all women ≤50 with a RS\u003e16. Based on the recent clinical-risk analysis, Ovarian Function Suppression (OFS) + endocrine therapy (ET) has been suggested as an alternative treatment for low clinical risk (clin-low) women ≤50yrs with an RS 16-25. This current analysis examines the updated treatment recommendations based on the interaction between patient age and clinical risk, and explores the impact that the 70-GS can have on adjuvant chemotherapy decisions for women ≤50 years of age. Methods: 70-GS risk of recurrence was determined for 21-GA intermediate patients by standard diagnostic testing (Agendia, Irvine, CA). Clinical risk was assessed using the MINDACT, modified Adjuvant Online! algorithm (Cardoso, NEJM 2016). The 70-GS High and Low Risk classification were subdivided by RS groups 18-20, 21-25, and 26-30 and by clinical risk stratification. Results: 181 patients in PROMIS were ≤50 yrs. Of those, 64% (116/181) were clin-low, and 35% (63/181) were high clinical risk (clin-high) (2 unknown). Among patients ≤50 yrs with RS 18-20, 60% (27/45) of clin-low and 56% (15/27) of clin-high were found to be 70-GS Low Risk. Among patients with RS 21-25, 55% (30/55) of clin-low and 30% clin-high (8/26) were Low Risk by the 70-GS. For patients ≤50 yrs with RS 26-30, 15% (4/27) were found to be 70-GS Low Risk. Of all patients with RS 26-30, 21% (32/156) were Low Risk by 70-GS. Conclusions: With the follow-up publication for TAILORx, incorporation of clinical risk in addition to age, RS group, and the assumed benefit of chemotherapy-induced menopause, has presented additional layers of complexity for physicians treating breast cancer. The current analysis demonstrates that 46% of women ≤ 50yrs with a RS 21-25 are 70-GS Low Risk, and based upon the prospective, randomized MINDACT* trial data, can safely avoid CT. Overall, the 70-GS can precisely identify 20-60% of women ≤ 50yrs with intermediate RS (18-30) as genomic Low Risk with excellent survival with ET alone (\u003e95% 5-yr DMFI [MINDACT]), who may otherwise be candidates for treatment with CT or OFS. *(Microarray in Node Negative and 1-3 Lymph Node Positive Disease May Avoid Chemotherapy) Citation Format: Michaela Tsai, Hatem Soliman, Shelly Lo, Rubina Qamar, Raye Budway, Ellis Levine, Pat Whitworth, Blanche Mavromatis, Robin Zon, Sarah Untch, Lisa Blumencranz, Joseph McKelley, William Audeh, PROMIS Investigators Group. Treatment recommendations in ER+ patients ≤ 50 years: Comparison of the 21-gene assay and 70-gene signature in the PROMIS study [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 P2-14-11.