Abstract PO5-22-12: Development and Validation of a Genomic Test to Predict Tumor Response of the Axillary Nodes after Neoadjuvant Chemotherapy (NAC) in Patients with HER2-negative Breast Cancer: Results of the AGO-35 trial

Abstract Background: De-escalation of axillary surgery in patients with lymph node-positive breast cancer is currently being tested in ongoing trials for patients with downstaged nodes after neoadjuvant chemotherapy (NAC). A proportion of such patients will achieve an excellent axillary node response to NAC, i.e. conversion to pathologic node-negative status after chemotherapy. Genomic prediction of tumor chemosensitivity before final surgery may identify which patients could safely undergo conservative surgical management of their regional lymph nodes. Methods: The AGO-35 (NCT0203274) is a prospective trial for patients with HER2 negative breast cancer scheduled for neoadjuvant chemotherapy that includes an anthracycline- based regimen followed by 3-4 cycles of taxanes. The LN predictor is a newly developed model for predicting the probability of pathological lymph node-positivity after NAC in triple-negative (TNBC) or hormone-receptor positive (HR+) breast cancer. To calculate the LN predictor, which is developed in microarray, we calibrated the normalized individual gene module and SET ER/PR from RNAseq to the Affymetrix U133A platform using independently combined total of 220 pairs of TNBC samples with both RNAseq and U133A microarray results. The logistic regression model is applied for the prediction of the binary outcome, pathological lymph node-positive or negative after NAC. The cut-points of LN predictor in TNBC and HR+ samples were pre-determined for each subtype of breast cancer and then, independent, blinded evaluation in the AGO-35 trial samples. Results: A total of 251 patients with HER2 negative breast treated with neoadjuvant chemotherapy were included. The LN predictor was validated on 189 qualified samples with wtRNA sequence. Statistical analysis of 181 samples is shown in Table 1. Conclusion: Preliminary results of the AGO-35 trial show that the newly developed molecular LN predictor may accurately predict chemosensitivity response to NAC, in high proportion of patients with TNBC. Supported by: Wissenschaftsfonds (FWF) KLI 406 EUBREAST study group AGO Österreich Breast Cancer Research Foundation (BCRF-0158) Table 1. Genomic prediction of chemosensitivity Citation Format: Florentia Peintinger, Thorsten Kühn, Hans-Christian Kolberg, Roland Reitsamer, Sabine Schmatloch, Elisa Sieghartsleitner, Lili Du, Andrea Berghold, W. Fraser Symmans. Development and Validation of a Genomic Test to Predict Tumor Response of the Axillary Nodes after Neoadjuvant Chemotherapy (NAC) in Patients with HER2-negative Breast Cancer: Results of the AGO-35 trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-22-12.