Publication: SABCS 2025, Presentation ID: PS3-08-17

Authors: Mahtani et al.

Title: HR+ HER2- Early Breast Cancer (EBC) Patients ≥70 with High Risk 70-gene Signature Benefit from (Neo)adjuvant Chemotherapy (CT): Real World FLEX Study

Introduction:

  • Women ≥ 70 years of age are less likely to receive chemotherapy (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.
  • Objective: To evaluate the utility of the 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- early-stage breast cancer (EBC).

Methods/Study Cohort:

  • The FLEX Study(NCT03053193) includes stage I-III pts with EBC who had MP performed and consented to full transcriptome and clinical data collection. A total of 6,237 HR+HER2- EBC pts were included. 1,145 were ≥70 (18%) and 4792 <70 (82%)

Results:

  • There were more MP Low and UltraLow 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 = 0.0115) (Table 2)
    • Pts aged ≥70 with MammaPrint 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).
  • Pts ≥70 (83.2%) were more likely to have 1 or more comorbidities to those <70 (58.0%, p<0.001; Table 3). A larger proportion of ≥70 pts vs <70 had a comorbidity score of 2 (25.2% vs 13.1%). Scores of 3+ were rare at 2.2% in both groups.
  • The 4-year DRFS for pts ≥70 with MP High Risk cancers showed a trend towards improved outcomes for those treated with CT vs. endocrine therapy alone, especially in H2 cancers (H1 88.5% vs 84.8%, p=0.031, H2 88.1% vs 78.3%, p=0.064) (Figure1).
  • In the interaction model, CT was associated with significantly improved DRFS in H1 (HR=0.51, p=0.015) and H2 (HR=0.35, p=0.009) pts ≥70 (Table 4).

Conclusions:

  • This Real-World Evidence study demonstrates that pts≥70 with HR+ HER2−EBCare less likely to receive CT than younger pts, despite a substantial number being classified as MammaPrint High.
  • Among pts ≥70 with MP High, CT use was associated with improved DRFS, after adjusting for 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- even after adjusting for comorbidities.
HR+ HER2- Early Breast Cancer (EBC) Patients ≥70 with High Risk 70-gene Signature Benefit from (Neo)adjuvant Chemotherapy (CT)