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 SETER/PR index in hormone receptor-positive 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 FEC followed by weekly paclitaxel (FEC+P) versus six cycles of FEC in lymph node-positive breast cancer. SETER/PR index was measured in all available HR+/HER2- tumor RNA samples using a pre-specified cutpoint (<0.75). The primary endpoint was 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). 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 low SETER/PR index, FEC+P significantly improved DRFI (HR 0.46; 95% CI, 0.22-0.95; p=0.035), with similar results after adjustment (HR 0.48; 95% CI, 0.24-1.00; 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 SETER/PR index as a predictive biomarker for paclitaxel-based chemotherapy and support its potential role in guiding regimen selection.