Abstract
Purpose
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.
Methods
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.
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 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).
Conclusions
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.
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Data availability
The datasets analyzed during current study are available from the corresponding author on reasonable request.
Abbreviations
- BCT:
-
Breast-conserving therapy
- BCS:
-
Breast-conserving surgery
- PBC:
-
Primary breast cancer
- IBTR:
-
Ipsilateral breast tumor recurrence
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Funding
This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research (B) (Grant Number 20H03668 to YH), Early-Career Scientists (Grant Number JP18K16292 to YH), and Research Grant for Young Scholars (to YH), the YASUDA Medical Foundation (to YH), the Uehara Memorial Foundation (to YH), the Medical Research Grants from the Takeda Science Foundation (to YH), and a Grant-in-Aid for Genome Research Project from Yamanashi Prefecture (to MO and YH).
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All Authors contributed to the study conception and design. Material collection and data collection were performed by HN, MI and analysis were performed by YH, KA and HM. The first draft of the manuscript was written by HN and MO, and all authors commented on previous version of the manuscript.
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This study was approved by the institutional review board in our hospital (No. 2018–6). We analyzed 22 cases in whom written informed consent for genomic analysis was obtained.
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Nakagomi, H., Inoue, M., Hirotsu, Y. et al. PIK3CA-AKT pathway predominantly acts in developing ipsilateral breast tumor recurrence long after breast-conserving surgery. Breast Cancer Res Treat 193, 349–359 (2022). https://doi.org/10.1007/s10549-022-06570-y
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DOI: https://doi.org/10.1007/s10549-022-06570-y