Abstract PS2-07-23: Predictive markers of distant recurrence from randomized chemotherapy regimens for hormone receptor-positive breast cancer patient in the PACS-01 trial

Abstract Background. SETER/PR index measures transcription that is related to estrogen and progesterone receptors (ER/PR) and not proliferation. Low SETER/PR index (below 0.75) predicted benefit from: 1) dose-dense, versus conventionally dosed, anthracycline-paclitaxel chemotherapy in the CALGB-9741 trial, and 2) the addition of 8 weekly doses of paclitaxel to anthracycline-based chemotherapy in the GEICAM/9906 trial. Therefore, we independently tested whether the SETER/PR index could predict benefit from the addition of docetaxel to anthracycline-based chemotherapy in patients from the PACS-01 trial (Roche et al, JCO 2006, PMID: 17116941) who had node-positive, hormone receptor-positive (HR+) cancer and subsequently received adjuvant endocrine therapy. In PACS-01, patients were randomized to receive weekly cycles of fluorouracil, epirubicin and cyclophosphamide (FEC) for six 3-weekly cycles (6FEC), versus three cycles of FEC followed by three 3-weekly cycles of docetaxel (3FEC + 3D). Methods. SETER/PR index was measured in HR+ tumor samples with the QuantiGene Plex bead-based hybridization assay (ThermoFisher) using an aliquot of RNA that was residual from prior testing of Recurrence Score (RS) at Genomic Health. Pre-defined analyses included the continuous SETER/PR index and the cut point SETER/PR index 0.75, as well as the continuous RS score and the cut-point RS 25, in patients who received adjuvant endocrine therapy after their chemotherapy. The primary endpoint was distant recurrence-free interval (DRFI). Interaction between chemotherapy regimens and each biomarker on DRFI was tested using a multivariable Cox proportional hazards model including the biomarker, the treatment arm and an interaction term between the treatment arm and biomarker. Results. There were 490 samples with evaluable SETER/PR index and RS from patients who received adjuvant endocrine therapy after their randomized chemotherapy treatment. There was a significant interaction between SETER/PR index as continuous score and treatment arm on DRFI (Pinteraction = 0.028), but not SETER/PR index dichotomized using cut point at 0.75 (Pinteraction = 0.668). Instead, the interaction was described by a cut point of SETER/PR index at 1.50 (Pinteraction = 0.013) and favored 6FEC when SETER/PR index ≥ 1.50 (HR 3.16, 95%CI 1.28-7.85), without significant difference between arms when SETER/PR index was below 1.50 (HR 0.83, 95%CI 0.51-1.35). Recurrence score did not predict outcomes between chemotherapy regimens using cut point RS at 25 (Pinteraction = 0.534) or as a continuous score (Pinteraction = 0.670). Exploratory analyses also illustrated a predictive value of SETER/PR index as continuous score and using cut-point at 1.50 in the subset of patients with 4 or more positive lymph nodes. Conclusions. SETER/PR index predicted between DRFI outcomes from an anthracycline-docetaxel regimen versus an anthracycline regimen without docetaxel, and the predictive cut point was different from previous studies that had assessed paclitaxel. Addition of docetaxel was less effective than continuing FEC treatments when breast cancer had high endocrine-related transcriptional activity (i.e., SETER/PR index ≥ 1.50). Overall, this provides additional new evidence that SETER/PR index values can predict which chemotherapy regimen might be more effective for a patient with HR+ breast cancer. Citation Format: F. PENAULT-LLORCA, A. LUSQUE, T. FILLERON, K. TRAN, L. DU, R. BAEHNER, F. DALENC, M. LACROIX-TRIKI, T. BACHELOT, F. ANDRE, P. BOUCHER, J. LEMONNIER, F. SYMMANS. Predictive markers of distant recurrence from randomized chemotherapy regimens for hormone receptor-positive breast cancer patient in the PACS-01 trial abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-07-23.