Background: Gefitinib exhibits antitumor activity in the patients with breast cancer, but the resistance to gefitinib in triple negative breast cancer (TNBC) is a new concern. Glutathione peroxidase 4 (GPX4) is a leading regulator of ferroptosis, which is of importance for the survival of TNBC cells. This study investigated GPX4-mediated ferroptosis in gefitinib sensitivity in TNBC.Methods: Gefitinib resistant TNBC cells MDA-MB-231/Gef and HS578T/Gef were constructed, and treated with lentivirus sh-GPX4 and ferroptosis inhibitor ferrostatin-1. GPX4 expression, cell viability and apoptosis were detected. Malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS) levels were evaluated. The levels of ferroptosis-related proteins ACSL4, PTGS2, NOX1 and FTH1 were detected. Subcutaneous tumor model was established in nude mice, and gefitinib was intraperitoneally injected. Apoptosis was detected by TUNEL staining and Ki-67 expression was detected by immunohistochemistry.Results: GPX4 was increased in gefitinib-resistant cells. After silencing GPX4, the inhibition rate of cell viability increased, the limitation of colony formation ability reduced, apoptosis rate increased, and the sensitivity of cells to gefitinib was improved. After silencing GPX4, MDA level and ROS production were significantly increased, while GSH level was decreased. Silencing GPX4 promoted ferroptosis. After inhibition of ferroptosis by ferrostatin-1, it revealed that inhibition of GPX4 promoted gefitinib sensitivity by promoting cell ferroptosis. In vivo experiments also showed that inhibition of GPX4 enhanced the anticancer effect of gefitinib through promoting ferroptosis.Conclusion: Inhibition of GPX4 stimulated ferroptosis and thus enhanced TNBC cell sensitivity to gefitinib.
Purpose The residual cancer burden index (RCB) was proposed as a response evaluation criterion in breast cancer patients treated with Neoadjuvant chemotherapy (NAC). This study evaluated the relevance of RCB with replase-free survival (RFS). MethodsThe clinical data of 254 breast cancer patients who received NAC between 2016 and 2020 were retrospectively collected. The relationship between clinicopathologic factors and RFS was evaluated using Cox proportional hazards regression models. RFS estimates were determined by Kaplan-Meier(K-M) analysis and compared using the log-rank test. Multivariate logistic regression analysis was used to evaluate the risk factors associated with RCB 0.Receiver operating characteristic (ROC) curves showed the potential of the RCB and MP grading systems as biomarkers for RFS. Results At a median follow-up of 26 months, 42 patients(16.5%) developed relapse. Multivariate Cox regression showed that older age (P=0.007), high Ki-67 expression (P=0.015) and a high RCB score(P=0.001) were risk factors for relapse. The outcomes of the multivariate logistic analysis indicated that RCB 0 (pathologic complete response [pCR]) was associated with HER-2-positive patients (P=0.002) and triple-negative breast cancer (TNBC) patients (P=0.009).In addition, the RCB and MP scoring systems served as prognostic markers for patients who received NAC, and their areas under the curve (AUCs) were 0.711 and 0.682, respectively. Conclusion These data suggest that RCB can be equally applied to predict RFS in Chinese patients with NAC, which may guide the selection of treatment strategies.
Background Sentinel lymph node biopsy (SLNB) acts as a vital role in the breast cancer surgery, and the identified number of sentinel nodes determines its accuracy to represent the status of axillae. There remain two tumor biopsy modes in breast cancer, preoperative and intraoperative biopsy. We compared the effect of the two different biopsies on the result of SLNB. Methods Patients with clinical stage T1-3, N0 tumor were enrolled in this study. 53% received preoperative tumor biopsy and 47% received intraoperative excisional biopsy. For search of the sentinel lymph node, patients received dual tracer injection. The number of SLNs detected and false negative rate were compared between groups. Results 204 patients were enrolled, 108 received preoperative tumor biopsy and 96 received intraoperative excisional biopsy. Among all the patients, 160 received ALND following SLNB. Preoperative tumor biopsy detected more SLNs than intraoperative biopsy (mean rank 113.87 vs. 90.9, p= 0.004). False negative rate in preoperative and intraoperative tumor biopsy was 3% and 18%, respectively. Conclusions Patients in preoperative tumor biopsy group could find more SLNs than intraoperative biopsy patients. False negative rate was also lower in preoperative biopsy group.
Background Sentinel lymph node biopsy (SLNB) acts as a vital role in the breast cancer surgery, and the identified number of sentinel nodes determines its accuracy to represent the status of axillae. There remain two tumor biopsy modes in breast cancer, preoperative and intraoperative biopsy. We compared the effect of the two different biopsies on the result of SLNB. Methods Patients with clinical stage T1-3, N0 tumor were enrolled in this study. 53% received preoperative tumor biopsy and 47% received intraoperative excisional biopsy. For search of the sentinel lymph node, patients received dual tracer injection. The number of SLNs detected and false negative rate were compared between groups. Results 204 patients were enrolled, 108 received preoperative tumor biopsy and 96 received intraoperative excisional biopsy. Among all the patients, 160 received ALND following SLNB. Preoperative tumor biopsy detected more SLNs than intraoperative biopsy (mean rank 113.87 vs. 90.9, p= 0.004). False negative rate in preoperative and intraoperative tumor biopsy was 3% and 18%, respectively. Conclusions Patients in preoperative tumor biopsy group could find more SLNs than intraoperative biopsy patients. False negative rate was also lower in preoperative biopsy group.
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