Abstract PS4-01: Predictor of benefit from dose-dense paclitaxel chemotherapy for patients with hormone receptor-positive HER2-negative breast cancer. A GEICAM/9906 sub-study

Abstract Background: SETER/PR index is a genomic test designed to measure endocrine transcriptional activity that is related to estrogen receptor (ER) and progesterone receptor (PR), but not proliferation. Higher values of SETER/PR index indicate greater endocrine transcriptional activity in the cancer. It was previously reported that levels of SETER/PR index below 0.75 predicted benefit from dose-dense (q2-week), versus conventional (q3-week) anthracycline-paclitaxel chemotherapy for patients (pts) with hormone receptor-positive (HR+) lymph node-positive breast cancer (BC) in the CALGB 9741 trial (Metzger et al, 2022, ASCO). Since that was the first report of a test that could predict benefit from a dose-dense taxane-based chemotherapy in HR+ BC, we sought to independently test its predictive validity. Therefore, we tested the SETER/PR assay at this predefined cutoff point in pts with HR+/HER2- lymph node-positive BC from the phase III GEICAM/9906 trial to predict benefit from weekly paclitaxel treatments after three cycles of q3-week anthracycline chemotherapy (FEC+P) compared to three additional anthracycline treatments (FEC). Methods: We conducted a blinded independent validation study in 647 HR+/HER2- tumor RNA samples from GEICAM/9906 BC pts (51.9% of the trial’s cohort). GEICAM translational laboratory sent the de-identified tumor RNA samples to the MDACC laboratory for blinded testing with results returned to the GEICAM statistician. Predefined cutoff point was SETER/PR index <0.75. Clinical endpoints were distant recurrence-free interval (DRFI) and overall survival (OS, secondary endpoint). Multivariable Cox proportional hazards models including SETER/PR index, treatment arm and their interaction term were used to calculate hazard ratios with 95% confidence interval (HR, 95%CI) and two-sided 0.05 as predefined level of significance. Results: Of 647 HR+/HER2- tumor samples, 567 (87.6%) passed quality control for the SETER/PR assay, with 279 from the FEC+P and 288 from the FEC treatment arm. SETER/PR index was below 0.75 in 92/567 tumors (16.2%), 44 (47.8%) in the FEC+P arm and 48 (52.2%) in the FEC treatment arm. Overall, there were 149 distant recurrence events and 144 deaths. There was significant interaction between SETER/PR status and treatment arm on DRFI (P=0.046), but not OS (P=0.352). For patients with SETER/PR below 0.75, treatment with FEC+P significantly improved DRFI (HR 0.46; 95%CI, 0.22–0.95, P=0.035), even when adjusted for menopausal status and ≤3 versus ≥4 nodes involved (HR 0.48; 95%CI, 0.24–1.00, P=0.049), but there was no difference between treatments benefit when SETER/PR index was ≥0.75 (HR 1.02; 95%CI, 0.70–1.47, P=0.931). Conclusion: In this GEICAM/9906 trial retrospective analysis, patients with node-positive HR+/HER2- BC that has low endocrine transcriptional activity (SETER/PR index <0.75) benefited from inclusion of weekly paclitaxel in their adjuvant chemotherapy. This result provides independent confirmation that SETER/PR index predicts benefit from dose-dense paclitaxel-containing chemotherapy. Clinical trial information: NCT00129922. Citation Format: Miguel Martin, Alvaro Rodriguez-Lescure, Lourdes Calvo, Eveline Chen, Manuel Ruiz-Borrego, Cesar A. Rodriguez, Noelia Martinez-Jañez, Emilio Alba, Kevin Tran, Ignacio Pelaez Fernandez, Isabel Alvarez, Miguel Angel Segui, Alberto de la Cruz, Vicente Valero, Antonio Anton-Torres, Raquel Andres, Kepa Amillano, Jose J. Ponce-Lorenzo, Severina Dominguez Fernandez, Jesus Herranz, Raul Rincon, Rosalia Caballero, Ana Santaballa Bertran, Angel Guerrero-Zotano, W. Fraser Symmans. Predictor of benefit from dose-dense paclitaxel chemotherapy for patients with hormone receptor-positive HER2-negative breast cancer. A GEICAM/9906 sub-study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS4-01.