Publication: ESMO Breast Cancer 2025

Authors: Brufsky, et al.

Title: The impact of the 80-gene signature on pCR and chemotherapy treatment decisions in early-stage breast cancer: A FLEX analysis

Background:

The BluePrint (BP), 80-gene signature, provides insight into the intrinsic subtype of early-stage breast cancer (EBC). This study evaluates pathological complete response (pCR) rates to neoadjuvant chemotherapy (NCT) by BP molecular subtype in MammaPrint ® (MP) High Risk tumors and the role of BP in guiding adjuvant chemotherapy (CT) treatment decisions using real-world data from patients with HR+ HER2- EBC enrolled in FLEX.

Methods:

Patients (pts) with HR+ HER2- MP High Risk (HR) tumors enrolled in FLEX (NCT03053193) were divided into NCT-treated with available pCR data (N = 401) and those with physician CT treatment recommendation data by BP (N = 868). Tumors were further classified as BP Luminal B or Basal. Clinical characteristics, pCR and treatment differences were assessed using Chi-Squared or Fisher’s exact tests

Results:

Among NCT-treated pts, BP classified 78% of tumors as Luminal B and 22% as Basal. LN+ was more common in Luminal B (66.1%) vs Basal tumors (34.8%; p < 0.001). More Basal tumors were grade 3 (91.7%) compared to Luminal B (43.0%; p < 0.001). Pts with Basal tumors were significantly more likely to achieve a pCR (38.2%) vs Luminal B (9.3%; p < 0.001). Of all pts in the treatment recommendation cohort (N = 868), 93% of the pts had BP Luminal B tumors and 7% had Basal. Among Basal, 88.1% were LN-, 41.5% were ER >50%, and 81.7% were grade 3, compared to 79.6% (p = 0.283), 97.2% (p < 0.001) and 18.8% (p < 0.001) for Luminal B, respectively. The Basal subtype was more frequently treated with CT (98.4%) and NCT (27.4%) compared to Luminal B (76.9%, p < 0.001; 11.9%, p = 0.006, respectively) and with a more aggressive CT regimen than docetaxel/cyclophosphamide (Basal: 54%, Luminal B: 25.7%, p < 0.001).

Conclusions:

Distinct pCR rates among breast cancer molecular subtypes underscore the utility of BluePrint in guiding treatment decisions. Despite all pts with MP HR, HR+ HER2- tumors qualifying for CT, pts with HR+ HER2- Basal tumors more often received CT, NCT, and more aggressive CT treatment regimens, compared to pts with Luminal B tumors. These findings suggest that physicians used BluePrint results to guide treatment decisions.