Publication: SABCS 2025, Presentation ID: PS2-07-03

Authors: O’Shaugnessy et al.

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

Introduction:

  • ABC trials found no significant differences in outcomes among patients with clinically high-risk HR+, HER2- breast cancer when comparing adjuvant therapy with taxane+cyclophosphamide (TC) vs. an anthracycline- and taxane-based regimen (TaxAC)
  • The MammaPrint®, 70-gene assay, identifies patients who derive (neo)adjuvant chemotherapy benefit2 and the BluePrint, 80-gene assay, further classifies genomic molecular cancer subtype
  • Here we provide an updated analysis3 within a propensity score matched population (PSM) examining the utility of MammaPrint in identifying patients with BluePrint Luminal B, HR+HER2- breast cancer likely to benefit from anthracycline+taxane (AC-T) vs. TC

Methods:

  • 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.
  • 3-yr invasive disease-free survival (IDFS)4, was compared within H1 and H2 groups using Kaplan-Meier analysis and log-rank tests, stratified 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 all patients, 1,106 had H1 and 153 had H2 HR+HER2- breast cancer
  • PSM resulted in no significant differences in clinical/pathologic features between the two chemotherapy groups within each H1 and H2 cohort (Tables 1-2)
  • For patients 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) (Figure 1)
    • The non-significant absolute difference in IDFS for patients with H1 tumors at 4- and 5-years remained <1%
  • In contrast, H2 patients treated with TC had a significantly worse 3-yr IDFS of 89.3% compared with 100% for AC-T-treated patients, with an absolute benefit of 10.7% (p = 0.048) (Figure 2)
    • At 4- and 5-years the absolute differences in IDFS for patients with H2 cancers were 8.1% and 13.7%, respectively, in favor of AC-T treatment
  • Multivariate Cox regression analysis within the H1 group showed no association with improved IDFS with AC-T, while the use of AC-T in patients with H2 showed a trend towards improved IDFS compared to TC, but did not reach significance likely due to sample size (Tables 3-4)

Conclusions:

  • In this PSM analysis of a non-randomized, prospective, real-world FLEX Study data with 3.2 years median follow-up, patients with H2, HR+HER2- cancer had significantly improved IDFS with AC-T compared to TC
  • Although adjusted analyses were limited by few events, the direction and magnitude of benefit remained consistent
  • In contrast, patients with H1 cancer did not benefit more from AC-T vs. TC
  • These findings further support the utility of MammaPrint in informing chemotherapy selection in patients with HR+HER2- breast cancer
ACT 3yr IDFS 2025