Abstract PS2-07-03: Improved 3-year IDFS with anthracycline-based therapy for patients with 70-gene signature High 2, Luminal B, HR+HER2- early-stage breast cancer

Abstract Background: The ABC trials evaluated the efficacy of taxane with cyclophosphamide (TC) vs anthracycline and taxane-based chemotherapy (AC-T) in patients (pts) with clinically high risk, HER2-negative (HER2-) breast cancer (BC), and observed no significant difference between these treatment regimens among pts with hormone receptor-positive (HR+) BC. The MammaPrint® (MP), 70-gene signature, identifies pts with early BC (EBC) who derive (neo)adjuvant chemotherapy (CT) benefit. To examine the utility of MP in identifying pts likely to benefit from AC-T, we provide an updated analysis of data presented at ASCO 2024 and evaluated 3-year (yr) outcomes among propensity-score matched (PSM) pts with MP High Risk, HR+HER2- BC who received adjuvant TC or AC-T on the prospective observational FLEX Study. Methods: The FLEX Study (NCT03053193) enrolled EBC pts who received standard of care MP with BluePrint® (BP) intrinsic subtyping. 1261 pts had MP High Risk, BP Luminal B, HR+HER2- EBC and received either adjuvant TC or AC-T (non-randomized) with 3.2 yrs median follow-up. High Risk was further stratified into High Risk 1 (H1) and High Risk 2 (H2). PSM was performed to balance differences in age, tumor size and nodal status between the TC and AC-T-treated pts for the H1 and H2 groups, separately. The 3-yr invasive disease-free survival (IDFS), as defined by STEEP 2.0, was compared within H1 and H2 groups using Kaplan-Meier analysis and log-rank tests, grouped by TC vs AC-T. Cox proportional hazards models were used to evaluate the effect of CT regimen and clinical features on survival within each group. Results: Among 1261 pts, 1107 had H1 and 154 had H2 HR+ HER2- BC. Pts who received TC (H1, n=818; H2, n=103) were PSM with pts who received AC-T (H1, n=289; H2, n=51), yielding a cohort of 578 pts with H1 and 102 with H2 BCs with no significant differences in clinical/pathologic features between the two CT groups within each of the H1 and H2 cohorts. For pts with H1 BC, no significant difference in 3-yr IDFS was observed between AC-T (95.6%) and TC (94.6%) treatment (p = 0.98; Table). In contrast, H2 pts treated with TC had a significantly worse IDFS of 89.3% compared with 100% for AC-T-treated pts, with an absolute benefit of 10.7% (p = 0.048). Multivariate Cox regression analysis within the H1 group showed no association with improved IDFS with AC-T, while the use of AC-T in H2 pts showed a trend towards improved IDFS compared to TC, but did not reach significance likely due to sample size. Conclusions: In this PSM analysis of non-randomized, real-world FLEX Study data with 3.2 yrs median follow-up, pts with H2 HR+HER2- EBC had significantly improved IDFS with AC-T compared to TC. In contrast, pts with H1 disease did not benefit more from AC-T vs TC. These findings further support the utility of MammaPrint in informing prognosis and CT selection in pts with HR+HER2- EBC. Citation Format: J. O'Shaughnessy, A. Brufsky, C. L. Graham, C. R. Osborne, R. L. Rahman, A. Elkhanany, E. A. Brown, L. P. Gold, N. M. Johnson, D. Giffoni, J. Alberty-Oller, R. L. Mahtani, H. Ramaswamy, N. Stivers, A. Menicucci, W. Audeh. Improved 3-year IDFS with anthracycline-based therapy for patients with 70-gene signature High 2, Luminal B, HR+HER2- early-stage breast cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-07-03.