Abstract Background Most breast cancer-related death is caused by recurrence and metastasis. Approximately 30% to 40% of patients will experience recurrence during their lifetime. Although the promising effect of endocrine therapy in ER-positive breast cancer, there are still about 30% of patients who ultimately die due to recurrence. In contrast to ER-negative, more than 50% of recurrences occur beyond five years (late recurrence, LR) in ER-positive breast cancer, which represents the proportion of early (ER, recurrence occur within five years) or even very early recurrence (VER, recurrence occur within one year in our preliminary results) are rare. In comparison with LR, the prognosis of ER and VER is poor and more aggressive; however, most studies focused on LR, including mechanisms, treatment, and genetic/immune profiles, few studies focused on ER, and even No studies concerned what we named VER. On the other hand, the introduction of a multigene prognostic test (MPT) can provide the dual role of prognostic and predictive to fulfill and strengthen the information in treatment decisions. However, there still existed some defects in the current MPT, including high cost, ethnic difference, and specificity for different time points of recurrence type. Thus, there is a huge gap in ER or even VER, and a critical unmet need to identify who is prone to recurrence for Asia breast cancer. Methods Fifty ER-positive patients with disease-free (DF, average follow-up 48 months), and 14 ER-positive patients with recurrence were enrolled in this study. Initially, three patients from 50 patients with DF and nine patients from 14 patients with recurrence were selected. In total of 12 patients (three patients for each group, including DF, VER, ER, and LR) were selected, and residual RNA samples from EndoPredict (EP) were analyzed by using the NanoString technique. Finally, raw data processing, normalization, and analysis were performed in the nSolver analysis software. Appropriate statistical analyses were performed using GraphPad Prism 9. Results In our preliminary results, we collected the data with EndoPredict and long-term follow-up records. By using the NanoString technique, we found some novel and unique target genes in different groups of recurrence. The expression of SERPINA1 was specific to disease-free (DF, average follow-up 48 months), CEACAM6 was overexpressed in LR group (average PFS 45 months), TGFB2 was only observed in VER group (average PFS 8 months), and AREG was co-existed in the group of ER (average PFS 23 months) and VER. Moreover, we compared the scores from a low-cost platform of immunohistochemical 4 (IHC4) and EndoPredict within 64 patients (average follow-up 48 months) and found a positive correlation between the IHC4 risk score and EPClin score in prognosis prediction. Conclusion To our knowledge, we provide the first preliminary results of novel gene targets at different time points of recurrence, especially for VER. We also found a positive correlation between the IHC4 risk score and EPClin score in prognosis prediction. The ability of prediction and mechanisms in recurrent breast cancer from these target genes will be validated in a large cohort and requires further investigations in the future. Citation Format: M. Hou, F. Chen, C. Li, C. Chiang. Potential genetic targets of recurrence at different time points in Asia breast cancer with NanoString and multigene prognostic test 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 PS3-03-27.
Hou et al. (Tue,) studied this question.