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We were greatly interested in Qu et al.‘s recent editorial, which discussed the de-escalation of surgery for Ipsilateral Breast Tumor Recurrence (IBTR) and the potential integration of genomic features with location and pathology to differentiate between true IBTR and second primary tumors [1]. However, the authors did not delve into the potential biological mechanisms behind the clinical observation that repeat breast-conserving surgery does not seem to compromise overall survival compared to total mastectomy. We would like to highlight emerging evidence suggesting that Breast-Conserving Therapy (BCT) may provide an overall survival (OS) advantage over mastectomy in IBTR cases among patients previously treated with BCS and RT. A recent meta-analysis lends strong support to this notion, revealing that undergoing repeat BCS, with or without repeat RT, correlates with improved OS (Risk Ratio = 1.040, 95% CI: 1.003–1.079; p = 0.032, I2 = 70.8%) [2]. Furthermore, Gentile et al. have reported compelling findings, demonstrating significantly improved Distant Disease-Free Survival (DDFS), OS, and Breast Cancer-Specific Survival (BCSS) in patients undergoing BCS for triple-negative or HER2-enriched IBTR when compared to mastectomy (p = 0.009, p = 0.002, p = 0.001, respectively) [3]. These results echo the growing body of evidence supporting the OS benefits of BCT over mastectomy in the initial treatment of early breast cancer [4].
We posit that a true IBTR represents a metastatic event initiated by circulating and disseminated tumor cells that undergo reactivation due to intrinsic and extrinsic factors, ultimately thriving in the primary site through mechanisms orchestrated by the tumor microenvironment. When the breast is removed via total mastectomy, these activated cells may seek an alternative metastatic niche in distant organs. Our hypothesis provides a potential explanation for the superior OS associated with second primaries compared to true IBTR [5].
References
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Tollan CJ, Pantiora E, Valachis A, Karakatsanis A, Tasoulis MK (2022) A systematic review and Meta-analysis on the role of repeat breast-conserving Surgery for the management of ipsilateral Breast Cancer recurrence. Ann Surg Oncol 29(10):6440–6453. https://doi.org/10.1245/s10434-022-12197-6Epub 2022 Jul 18. PMID: 35849299
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De la Cruz Ku G, Karamchandani M, Chambergo-Michilot D, Narvaez-Rojas AR, Jonczyk M, Príncipe-Meneses FS, Posawatz D, Nardello S, Chatterjee A (2022) Does breast-conserving Surgery with Radiotherapy have a better survival than mastectomy? A Meta-analysis of more than 1,500,000 patients. Ann Surg Oncol 29(10):6163–6188. https://doi.org/10.1245/s10434-022-12133-8Epub 2022 Jul 25. PMID: 35876923
Witteveen A, Kwast ABG, Sonke GS, IJzerman MJ, Siesling S (2015) Survival after Locoregional recurrence or second primary Breast Cancer: impact of the disease-free interval. PLoS ONE 10(4):e0120832. https://doi.org/10.1371/journal.pone.0120832
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Mokbel, K., Alamoodi, M. “Enhancing survival outcomes through breast-conserving therapy in ipsilateral breast tumor recurrence: insights into metastasis and treatment strategies”. Breast Cancer Res Treat 204, 187 (2024). https://doi.org/10.1007/s10549-023-07180-y
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DOI: https://doi.org/10.1007/s10549-023-07180-y