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 ยฎ (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 Fisherโ€™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.