e12577 Background: Cancer genomic sequencing has fundamentally advanced our understanding of the basic biology of this disease, and more recently, has offered method to guide and evaluate treatment in clinic. We performed whole-genome sequencing (WGS) on three consecutive tissue and blood samples from breast cancer patients: diagnosis, post-neoadjuvant chemotherapy, recurrence after curative resection. Methods: We performed WGS to compare the genetic profiles of the primary, surgical and recurrent samples (tissue and blood) to determine: (1) how closely related the genetics are among the primary, post-neoadjuvant chemotherapy, and the recurrent tumors, (2) whether there are variations in mutational processes among the primary, post- neoadjuvant chemotherapy, and recurrent tumor. WGS was performed on three patients for whom both tissue and blood were available at diagnosis, at surgery after neoadjuvant chemotherapy and at a recurrence. Results: As a result of somatic protein coding variant analysis, PIK3CA mutation was confirmed at the time of diagnosis tissue in all cases. Mutations were found at p.E545K in patient 14, p.R916C in patient 18, and p.R916C in patient 3. Among these, patients 14 and 18 had PIK3CA mutations even at the time of recurrence. In patient 14, the same PIK3CA mutation was found in 3 consecutive samples, but in patient 18, it changed from p.R916C at diagnosis to p.G480E at relapse. Furthermore, functional enrichment analysis identified a common NRAGE signaling system in the cfDNA. The NRAG pathway was found in the blood at diagnosis, surgery, and recurrence in all three patients. Conclusions: This study was a proof-of-concept study, in which we hypothesized that NRAGE/JNK and PI3K/AKT signaling pathways are involved in breast cancer recurrence and treatment response through WGS of consecutive samples. Further research is ongoing with larger numbers of patients.