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PubMed · 42189890

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

Miguel Martín·Alvaro Rodriguez-Lescure·Cristina Reboredo·Eveline Chen·Manuel Ruiz-Borrego·Ana Santaballa Bertran·Cesar A Rodríguez·Noelia Martinez-Jañez·Emilio Alba·Kevin Tran·Ignacio Pelaez Fernandez·Isabel Álvarez·Miguel A Seguí·Alberto de la Cruz·Vicente Valero·Antonio Antón-Torres·Raquel Andrés·Kepa Amillano·José J Ponce-Lorenzo·Severina Dominguez Fernandez·Jesus Herranz·Raul Rincon·Rosalía Caballero·Angel Guerrero-Zotano·Federico Rojo·W Fraser Symmans
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Abstract

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 &#x2265;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.

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HumansFemalePaclitaxelBreast NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsReceptors, EstrogenChemotherapy, AdjuvantBiomarkers, TumorReceptors, ProgesteroneCyclophosphamideMiddle AgedErb-b2 Receptor Tyrosine KinasesEpirubicinAdultFluorouracilTreatment OutcomeAgedPrognosisRetrospective StudiesJournal ArticleRandomized Controlled Trial

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Miguel Mart&#xed;n, Alvaro Rodriguez-Lescure, Cristina Reboredo, Eveline Chen, Manuel Ruiz-Borrego, Ana Santaballa Bertran, Cesar A Rodr&#xed;guez, Noelia Martinez-Ja&#xf1;ez, Emilio Alba, Kevin Tran, Ignacio Pelaez Fernandez, Isabel &#xc1;lvarez, Miguel A Segu&#xed;, Alberto de la Cruz, Vicente Valero, Antonio Ant&#xf3;n-Torres, Raquel Andr&#xe9;s, Kepa Amillano, Jos&#xe9; J Ponce-Lorenzo, Severina Dominguez Fernandez, Jesus Herranz, Raul Rincon, Rosal&#xed;a Caballero, Angel Guerrero-Zotano, Federico Rojo, W Fraser Symmans. 2026-09-01. Sensitivity to Endocrine Therapy Index Predicts Benefit from Weekly Adjuvant Paclitaxel for Hormone Receptor-Positive Breast Cancer in the GEICAM/9906 Trial.. https://doi.org/10.1158/1078-0432.ccr-26-0177

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