Abstract PS3-08-17: HR+ HER2- Early Breast Cancer (EBC) Patients ≥70 with High Risk 70-gene signature benefit from (Neo)adjuvant chemotherapy (CT): Real World FLEX Study

Abstract BACKGROUND: Women ≥70 are less likely to receive CT due to quality-of-life concerns and comorbidities. These patients (pts) are underrepresented in studies assessing the utility of genomic profiling to guide CT decisions. To identify the utility of a 70-gene recurrence risk assay MammaPrint (MP) we examined the relationship of age (≥70 vs <70), comorbidities, and treatment outcomes stratified by MP result in pts with HR+HER2- EBC. METHODS: The FLEX Study (NCT03053193) includes stage I-III pts with EBC who had MP performed and consented to full transcriptome and clinical data collection. Clinical characteristic differences between age groups were assessed by Chi-squared, Fisher’s exact, or Wilcoxon-Mann-Whitney tests. 4-year (yr) DRFS was assessed using Kaplan-Meier survival analysis. Log-rank tests assessed differences in endpoints between treatment groups. Comorbidity scoring assigned conditions into 7 categories. Pts were assigned 1 point for each category with a reported condition; multiple conditions in a single category counted as 1 point (Table). A multivariate Cox regression model evaluated predictors of DRFS in pts ≥70, adjusting for treatment-genomic risk interactions. Results: A total of 6237 HR+HER2- EBC pts were included. 1145 were ≥70 (18%) and 4792 <70 (82%). MP results showed higher rates of low-risk tumors in the ≥70 vs <70 group (Ultralow 15.2% vs 14.6%, Low 41.5% vs 39.5%, High 1 (H1) 37.4% vs 36.7%, and High 2 (H2) 6.0% vs 9.2%, p = 0.013). Pts ≥70 vs <70 were less likely to receive (neo)adjuvant CT (26.0% vs 42.5%, p<0.001). 16.7% of pts ≥70 had no comorbidities, vs 42.0% of those <70 (p<0.001). A larger proportion of ≥70 pts vs <70 had a comorbidity score of 2 (25.2% vs 13.1%, p<0.001). Scores of 3+ were rare at 2.2% in both groups. Pts aged ≥70 with High -Risk cancers were less likely to receive CT than those <70 (H1: 49.4% vs 77.1%, H2: 72.1% vs 90.9%, p<0.001). The 4-year DRFS for pts ≥70 with High -Risk cancers trended toward superiority for those treated with CT vs endocrine thx alone, especially in H2 cancers (H1 88.5% vs 84.8%, p=.031, H2 88.1% vs 78.3%, p=.064). In multivariate analysis, CT was associated with improved DRFS in H1 (HR=0.51, p=0.015) and H2 (HR=0.35, p=0.009) pts ≥70. CONCLUSION: This Real-World Evidence study demonstrates that pts ≥70 with HR+HER2− EBC are less likely to receive CT than younger pts, despite a substantial number being classified as MP High. Among pts ≥70 with MP High, CT use was associated with improved DRFS, even in the presence of comorbidities. While the unadjusted difference in 4-year DRFS for the H2 subgroup did not reach significance, multivariate analysis showed a significant association between CT and reduced recurrence risk. These findings suggest that MP may provide additional risk information supporting individualized treatment decisions in pts ≥70 with HR+HER2- EBC even with underlying comorbidities. Citation Format: R. Mahtani, H. Wildiers, S. Lin, S. Ana, A. Schreiber, L. Carcas, N. Dempsey, V. Poillucci, M. Landon, C. Dreezen, H. Ramaswamy, W. Audeh, J. O'Shaughnessy. HR+ HER2- Early Breast Cancer (EBC) Patients ≥70 with High Risk 70-gene signature benefit from (Neo)adjuvant chemotherapy (CT): Real World FLEX Study [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 PS3-08-17.