Prevention of in Situ Recurrence and Distant Metastasis in Feline Mammary Carcinoma Treated with Plasmonic Photothermal Therapy

Abstract

Abstract Background Clinical studies indicated the role of Breast Cancer Stem Cells (BCSCs) with the phenotype of CD44+/CD24− and/or CD133+ in the promotion of invasive and metastatic mammary tumors. Where BCSCs are resistant against the conventional chemo and radiotherapies, the gold nanorods (AuNRs)-mediated plasmonic photothermal therapy (PPTT) selectively eradicated BCSCs. A change in CTCs number predicts response to therapy. Among felines, most of the queens with mammary carcinoma (MC) exhibit an aggressive metastatic phenotype. Thus, indicated the importance of developing a rapid, accurate and noninvasive approach for prediction and monitoring of metastasis in cats. In this study, we investigated for the first time the anti-tumor activity of AuNRs PPTT by Flow Cytometry Analysis (FCA) of the circulatory BCSCs in cats with spontaneous metastatic and non-metastatic forms of MC. Methods The PPTT was applied on each animal in this investigation either alone (GA) or in combination with mastectomy (GB). PB was collected from all diseased cats before the treatment and 2 weeks after every PPTT cycle. BCSCs were identified in each sample as CD133+ in one test and CD44+/CD24− combination in another test using the FCA. Cells counts were compared between groups and across time. The correlation between BCSCs values and metastasis was evaluated using Spearman's correlation test. Survival analysis was performed, and prognostic cutoff points were established using ROC analysis. Results With survival rate of 50%, the non-metastatic cats in GA revealed complete tumor ablation 6–8 weeks of treatment and complete wound healing in GB, no in situ recurrence or distant metastasis over the observation period with a statistically significant drop in cBCSCs counts (P = 0.00512). Progression-free survival (PFS) was of a mean of 9 months (GA) and 6.6 months (GB) with median overall survival (OS) of 10.5 months (GA) and 9.5 months (GB). Lung metastasis persisted in metastatic cats in GA &GB with short PFS of 4 months. Prognostic significant cutoff values were > 996 for (CD44+/CD24−) phenotypes and > 110 for CD133+ cells. Conclusion BCSCs are highly susceptible to PPTT in non-metastatic queens unlike the metastatic cats as a treatment modification is required to systemically deliver the AuNRs to the metastatic sites. FC enumeration of cTCs with the CD44+/CD24− or CD133+ phenotypes has a prognostic value as an accurate and non-invasive method for therapy monitoring in FMC.