Publication: ASBRS 2025

Authors: Thompson et al.

Title: Real World Evidence of MammaPrint® and BluePrint® utility for informing axillary surgery decisions in the neoadjuvant setting

Introduction:

  • Decisions regarding the extent of axillary surgery in HR+HER2- early-stage breast cancer (EBC) are primarily based on clinical factors, including age, T-stage, and N-stage
  • The ACOSOG Z00111 trial found sentinel lymph node dissection (SLND) noninferior to axillary lymph node dissection (ALND) for T1-2 and 1-2 LN+ for 10-year Overall Survival, however, the role of genomics for axillary surgery decision-making remains unclear
  • The NBRST2,3 and I-SPY24 trials have shown that the risk of distant recurrence and molecular subtyping signatures, MammaPrint and BluePrint, can predict distinct pathological Complete Response (pCR) rates to neoadjuvant chemotherapy (NCT) in EBC
  • To identify the role of genomic profiling in axillary decision making in FLEX, we evaluated the association of MammaPrint and BluePrint with the likelihood of achieving pCR (ypT0/isN0) and avoiding ALND in patients with HR+HER2- EBC

Methods:

Study Cohort

  • Patients with HR+HER2- tumors treated with NCT with available surgical treatment information enrolled in the ongoing prospective, observational FLEX Trial (NCT03053193), were included in this study (N = 603)

Results:

  • Most patients were postmenopausal (61%), had T2+ tumors (78%), had nodal involvement (59%), and were treated with anthracyclines (63%) . Most H2 tumors (77%) had ER% staining ≥10% and were more likely to be Grade 3 (79%; p<0.001), compared to H1 and Low-Risk tumors (Table 1)
  • Patients with H2 tumors were significantly more likely to achieve a pCR (27.5%) compared to Low-Risk (4.3%) or H1-Risk (8.1%; p<0.001). Addition of BluePrint showed patients with H2/Basal-Type tumors had the highest pCR (39.3%; p<0.0001) (Figure 1)
  • Multivariate analysis revealed that patients with H2 (OR=3.16, 95% CI 1.43-7.28, p=0.005; data not shown) or H2/Basal-Type tumors were significantly more likely to achieve pCR (OR=5.18, p=0.001) when accounting for menopausal status, T-stage, nodal status, and grade (Table 2)
  • H2 was significantly more likely to avoid ALND (74.8%) compared to patients with Low-Risk (58.3%) and H1 tumors (67.9%; p=0.018). BluePrint revealed patients with H2/Basal-Type had the highest rates of undergoing SLND (Figure 2)
  • Multivariate analysis showed that patients with H2/Basal-Type tumors had a significantly lower Odds Ratio of undergoing ALND (OR=0.31; p=0.031), while LN+ at presentation was strongly associated with undergoing ALND (OR=3.45, p<0.001) (Table 3)

Conclusions:

  • MammaPrint and BluePrint not only predict response to NCT in HR+HER2- EBC but also correlate with axillary surgery outcomes. Patients with H2 or Basal-Type tumors were significantly more likely to achieve pCR and more likely to avoid ALND
  • I-SPY24 showed that patients with MammaPrint H2 tumors achieve even greater pCR rates with emerging treatments such as immunotherapy, which is currently under evaluation in the Phase-III SWOG S2206 (NCT06058377) trial
  • These results suggest that MammaPrint/BluePrint can inform neoadjuvant planning and highlight the importance of using MammaPrint/BluePrint on core needle biopsies in patients with HR+HER2- EBC to help enable downstaging and less invasive axillary surgery to increase the pCR rates in Luminal cancers.
  • Prognostic value of pCR vs no pCR may be different by subtype, and follow-up for outcomes such as DMFS and DMFI is a future goal within the FLEX trial.