Sensitivity to Endocrine Therapy Index Predicts Benefit from Weekly Adjuvant Paclitaxel for Hormone Receptor-Positive Breast Cancer in the GEICAM/9906 Trial.

PURPOSE: To independently validate that low endocrine transcriptional activity measured by the sensitivity to endocrine therapy (SETER/PR) index in hormone receptor-positive (HR+) breast cancer predicts benefit from dose-dense paclitaxel chemotherapy within a second prospective-retrospective biomarker study.

EXPERIMENTAL DESIGN: We conducted a blinded, prospective-retrospective biomarker analysis within the GEICAM/9906 trial (NCT00129922), which compared adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) followed by weekly paclitaxel (P) versus six cycles of FEC in lymph node-positive breast cancer. The SETER/PR index was measured in all available HR+/HER2- tumor RNA samples using a prespecified cut point (<0.75). The primary endpoint was the distant recurrence-free interval (DRFI); secondary endpoints were overall survival (OS) and breast cancer-specific survival (BCSS).

RESULTS: Of 647 HR+/HER2- tumors, 567 (87.6%) passed assay quality control (279 FEC + P; 288 FEC). A low SETER/PR index was identified in 92 tumors (16.2%). There was a significant interaction between SETER/PR status and treatment on DRFI (P = 0.046). Among patients with a low SETER/PR index, FEC + P significantly improved DRFI [hazard ratio (HR), 0.46; 95% confidence interval (CI), 0.22-0.95; P = 0.035], with similar results after adjustment (HR, 0.48; 95% CI, 0.24-1; P = 0.049). No treatment benefit was observed for SETER/PR ≥0.75 (HR, 1.02; 95% CI, 0.70-1.47; P = 0.931). Differences in OS and BCSS did not reach significance.

CONCLUSIONS: Low endocrine transcriptional activity predicts benefit from adding weekly paclitaxel to anthracycline-based adjuvant chemotherapy in HR+/HER2- breast cancer. These findings independently validate the SETER/PR index as a predictive biomarker for paclitaxel-based chemotherapy and support its potential role in guiding regimen selection.