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

Ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy is seen after a long interval, but the clinical classification of Residual Tumor Recurrence (RR) or Double Primary (DP) needs to be validated. We used genome profiling to identify the genetic alterations associated with IBTR.

Among 1881 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 identified, it was classified as genomic residual recurrence gRR, and when no shared mutations identified, it was classified as gDP. The differences between clinical and genomic classification were compared. Furthermore, the pathway of the genes which were responsible for recurrence was also examined.

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 significant 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).

Genome profiling revealed that abnormalities in the PIK3CA-AKT pathway in long-term residential recurrences and are a crucial molecular group in the development of IBTR.