Association of preoperative and postoperative circulating tumour DNA (ctDNA) with PIK3CA gene mutation with risk of recurrence in patients with non-metastatic breast cancer

Background Circulating tumour DNA (ctDNA), contains tumour-specific gene mutation in blood circulation and could aid in postoperative risk stratification of non-metastatic breast cancer. In this study, we investigated the feasibility of detecting PIK3CA gene mutations in ctDNA in the preoperative (preop) and postoperative period (postop), and its prognostic significance in patients with breast cancer. Methods A cohort of patients with breast cancer undergoing curative surgery with available blood samples preoperatively and postoperatively (PO) at either of PO time point; PO week 1–2, PO week 3–4 and PO weeks 5–12 were enrolled. PIK3CA gene mutations at exons 9 and 20 were detected in ctDNA with High resolution melting (HRM) PCR and Allele specific fluorescence probe-based PCR. Results A total of 62 patients (age, median (IQR), 51.50 (45.0–65.0) years), with a median follow-up of 90 months (interquartile range (IQR),60–120 months) were enrolled. In total, 25 (40.3%) and 22 (35%) patients with breast cancer had detectable PIK3CA mutations in ctDNA in preop and postop period, respectively. PIK3CA mutations in ctDNA in postop period (hazard ratio (H.R: 18.05, p = 0.001) were negative prognostic factor for recurrence-free survival (RFS) and overall survival (O·S) (H.R: 11.9, p = 0.01) in patients with breast cancer. Subgroup analysis of ctDNA indicate that positive ctDNA in both preop/postop period and post op period only were found to have prognostic effect on RFS and O·S (RFS; p < 0.0001, O·S; p = 0.0007. Moreover, ctDNA-based detection preceded clinical detection of recurrence in patients with an average lead time of 12.00 months (IQR:20–28.5 months) across all breast cancer subtypes. Conclusion We highlighted the prognostic ability of ctDNA in patients with breast cancer in perioperative period. However, future prospective studies are needed to assess the utility of ctDNA in breast cancer.