Real-world evidence from FLEX: Utility of MammaPrint in guiding treatment planning for patients aged 70 and older with early-stage breast cancer.

11175 Background: Older women (≥70) are less likely to receive chemotherapy (CT) due to quality-of-life concerns. Additionally, older patients are underrepresented in studies assessing the utility of genomic profiling in guiding CT decisions, thus guidelines around neo/adjuvant CT for this population are less clear. To identify the utility of the MammaPrint (MP) 70-gene and BluePrint (BP) 80-gene assays in informing treatment decisions in an elderly population, we examined the relationship of age ( ≥70 vs.<70) and treatment outcomes stratified by MP/BP subtypes in pts with HR+ HER2- EBC. Methods: The prospective, observational FLEX Study (NCT03053193) includes stage I-III pts with early-stage breast cancer (EBC) who received MP with or without BP testing and consented to full transcriptome and clinical data collection with therapy data available. Differences in the distribution of clinical characteristics between age groups were assessed by Chi-squared, Fisher’s exact, or Wilcoxon-Mann-Whitney tests. The endpoint recurrence-free interval (RFI) was defined as time to local, regional, or distant recurrence or breast cancer related death Kaplan-Meier survival analysis and log-rank tests were used to assess differences in endpoints between treatment groups. Results: A total of 4,519 HR+, HER2- EBC pts were included, with 1,047 ≥70 (23.2%) and 3,472 <70 (76.8%). Patients ≥70 were significantly less likely to present with high grade tumors and lymph node involvement than those <70 (12.8% vs 16.2% grade 3, p=.022; 20.6% vs 24.2% node positive, p=.017, respectively). The MP risk group distribution showed a significantly higher proportion of low genomic risk (Ultralow or low risk) tumors in the ≥70 vs. <70 group (Ultralow (UL) 14.7% vs 14.9% , Low 41.2% vs 38.7% , High 1 (H1) 37.3% vs 36.9% , and High 2 (H2) 6.8% vs 9.5% , p 0.048, respectively). Patients ≥70 with MP High Risk tumors were less likely to receive CT compared to those <70 (H1 55.8% vs 73%, p<0.001; H2 72.6% vs 82.2%, p=0.07, respectively). When evaluating 3-year RFI, the ≥70 pts with MP High Risk cancer trended towards better outcomes with CT than those receiving endocrine therapy only, especially in H2 cancers (H1 97% vs 94% , p=.137, H2 90% vs 79% , p=.078, respectively). Conclusions: This study underscores the potential CT benefits in MP H2 HR+ HER2- EBC pts ≥ 70 who may forgo treatment due to overall health and quality of life concerns. Notably, in MP H2 pts, the absolute improvement in 3-year RFI of 11% with neo/adjuvant CT in women ≥ 70 suggests that for many pts, the benefit outweighs the risks. Of note, this H2 CT benefit is similar to that observed in a group of 1000 pts with a median age of 59 recently reported (Brufsky, et al. SABCS 2024, P2-08-12). Patient centered discussions on performance status, comorbidities, and genomic profiling of HR+ HER2-EBC as well as the potential benefit from CT should guide personalized treatment. Clinical trial information: NCT03053193 .