Abstract Background: For postoperative follow-up of breast cancer, only annual MMG is recommended, commonly in guidelines around the world. Early detection of metastasis and recurrence has been considered of little significance. However, there have been remarkable advances in the development of new drugs, and with the improved accuracy of imaging tests for early detection and recent innovations in MRD assay technology, the importance of early detection of metastasis and recurrence in other cancer tumors is being emphasized. Methods: The INSPIRE trial (Intensive follow (IF) vs. standard follow (SF) post-operative surveillance in high-risk breast cancer patients; JCOG1204) is a randomized phase III study due to confirm the superiority of IF in terms of overall survival (OS) in high-risk breast cancer patients after radical surgery. Eligible participants were from 20 to 70 years old and had undergone radical breast and axillary surgery. Patients were randomized 1:1 to the SF arm (annual MMG and tumor markers) or the IF arm (annual MMG, whole-body CT or PET/CT every 6 months until 3 years and every 12 months until 5 years after surgery, and tumor marker every 3 months until 3 years and 6 months until 5 years after surgery). Adjustment factors: ER and HER2 status, with/without preoperative chemotherapy, institutions. Primary endpoint: OS. Key secondary endpoints: disease free survival, relapse-free survival (RFS), distant metastasis-free survival (DMFS). Five-year follow-up was completed for all enrolled patients. Data cut-off is Jan.2025. Results: From Nov 2013 to Jan 2020, 1034 pts were enrolled. 516 and 518 were assigned to SF and IF, respectively. Median follow up time is 82.9 (range: 0.5-130.9) months. The patient’s characteristics were well balanced between two arms: median age 53 (range: 23-70) years, PS 0/1:1018/16, pre/post menopause: 486/548, median tumor size: 3.0 (range:0-23 cm), stage 1A/2A/2B/3A/3B/3C: 78/262/346/153/83/110, ER+/-: 617/417, HER2+/-: 218/816, preoperative chemo +/-: 596/438, 7Y RFS: 73.0% vs 73.6% in SF and IF arm, respectively (p=0.999, 95% confidence interval CI:0.79-1.26). 7Y DMFS: 74.1% vs 75.5% in SF and IF arm, respectively (p=0.974, 95% CI: 0.76-1.24). The duration to recurrence/distant recurrence is 29.3/31.7 and 24.0/24.1 months in SF and IF, respectively. Lead times (the difference between SF and IF) of all and each subtype are shown in Table. Conclusion: There was no significant difference in RFS/DMFS between IF and SF arm. Recurrence was detected earlier by IF compared to SF, and the median time to recurrence was longer in luminal type than in TN type. However, the lead times were similar. The results of continued follow-up are awaited to see if this will lead to an improvement in overall survival, which is the primary endpoint. Citation Format: T. Hojo, N. Masuda, H. Iwata, A. Yoshimura, T. Ueno, M. Tsuneizumi, T. Onishi, H. Matsumoto, Y. Yanagita, M. Sawaki, H. Kawabata, S. Takayama, H. Shigematsu, T. Fujisawa, F. Hara, R. Kajikawa, K. Sasaki, T. Shien. Randomized phase III study comparing intensive follow-up with standard follow-up in post-operative high risk breast cancer INSPIRE trial: JCOG1204: the early analysis of Relapse-free survival and Onset of recurrence 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 PS1-06-06.
Hojo et al. (Tue,) studied this question.