PIK3CA-AKT pathway predominantly acts in developing ipsilateral breast tumor recurrence long after breast-conserving surgery

Abstract

Purpose: Ipsilateral Breast Tumor Recurrence (IBTR) after breast-conserving therapy is seen after a long interval, but the clinical classi cation of Residual Tumor Recurrence (RR) or Double Primary (DP) needs to be validated. We used genome pro ling to identify the genetic alterations associated with IBTR.Methods: Among 1,881 breast cancer patients treated with breast-conserving therapy between 1999 and 2018, IBTR occurred in 52 patients (2.8%). Of these 22 patients who consented for genomic analysis of Primary Breast Cancer ( T1) and IBTR (T2) were studied. When the same gene mutations in T1 and T2 were identi ed, it was classi ed as genomic residual recurrence gRR, and when no shared mutations identi ed, it was classi ed as gDP. The differences between clinical and genomic classi cation were compared. Furthermore, the pathway of the genes which were responsible for recurrence was also examined.Results: Of 13 clinically diagnosed RRs (cRRs), 11 were gRR and 2 were gDPs, while of 9 cDPs, 6 were gDP and 3 gRR, with a match rate of 17/22 (77%). We searched for genes involved in IBTR: PIK3CA-AKT pathway mutations were found in 12 of 14 gRRs (86%) in T1, and only 2 of 8 gDPs (25%) with signi cant difference (p=0.004). When both of PBC and IBTR compared, PIK3CA-AKT pathway abnormalities were 24/28 (86%) in the gRR and 5/16 (31%) in the gDP (p<0.001).Conclusions: Genome pro ling revealed that abnormalities in the PIK3CA-AKT pathway in long-term residential recurrences and are a crucial molecular group in the development of IBTR.

Omission of axillary surgery for ipsilateral breast tumor recurrence with negative nodes after previous breast-conserving surgery: is it oncologically safe?

“…In this study, IBTR was defined as an invasive carcinoma that occurred after BCS in the ipsilateral breast without clinical-radiologic evidence of regional disease, and no distinction was further analyzed between the two types of IBTR—true recurrence and new primary tumor [ 12 , 13 ]. The procedure of the BCS technique in our center was described previously [ 11 ].…”