ObjectiveTo summarize the latest advances in copper and cuproptosis in the field of breast cancer, and to provide a reference for clinical treatment decisions. MethodThe literatures related to copper and cuproptosis in recent years were read and summarized, and the research progress on the role of copper in breast cancer, the application of cuproptosis in the diagnosis and treatment of breast cancer were reviewed. ResultsCuproptosiswas a novel form of programmed cell death, which occurred via direct binding of copper to lipoylated components of the tricarboxylic acid (TCA) cycle, this resulted in lipoylated protein aggregation and subsequent iron-sulfur cluster protein loss, leading to proteotoxic stress and ultimately cell death. Cuproptosis induced proliferation and migration of breast cancer cell , mediated personalized immunotherapy, and participated in endocrine and chemotherapeutic drug resistance. ConclusionExploring the mechanism of cuproptosis provides potential applications for subsequent immunotherapy, endocrine therapy, and chemotherapy for breast cancer, leading to new effective strategies for patients.
Objective To study the long-term effect of neoadjuvant chemotherapy on advanced breast cancer. Methods The CAF neoadjuvant chemotherapy 〔CTX 500 mg/m2（1st day, 8th day), 5-FU 500 mg/m2（1st day, 8th day), and ADM 30 mg/m2 (1st day) every 3 weeks〕 was carried out in 31 breast cancer patients (stageⅢ,Ⅳ) for 2 cycles before operation, compared with 30 patients (stage Ⅲa) whose therapies were never done and operations could be feasible. Results The overall response rate was 87.1%(27/31). The stages of 19 patients among 31 (61.3%) declined (6 patients to stage Ⅲa, 8 to stageⅡb, 4 to stageⅡa, 1 to stage 0, 1 to complete response and none to pathological complete response). The diseasefree survival time of the patients was 56.3 months which was obviously longer than that of the patients without neoadjuvant chemotherapy (43.5 months, P＜0.05). The 5-year diseasefree survival rate of the patients with neoadjuvant chemotherapy was 38.7% which was a little higher than that (33.3%) of the patients without the chemotherapy, and the two groups had no significant difference. Conclusion The neoadjuvant chemotherapy can reduce the stages of patients with advanced breast cancer, obviously prolong the diseasefree survival time of patients, and reduce or delay recurrence or metastasis.
ObjectiveTo investigate the regulatory mechanism of thioredoxin binding protein (TXNIP)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathway in the occurrence and development of breast cancer.MethodsThe resected 15 cases of breast cancer tissues and their adjacent tissues in our hospital from September 2019 to June 2020 were selected, and the immunohistochemistry was used to detect the expression levels of TXNIP and NLRP3 in breast cancer and its adjacent tissues. Three kinds of breast cancer cell lines (MDA-MB231, MCF-7 and SKBR3) and normal breast epithelial cell line (HMEC) were collected. Western blot was used to detect the relative expression levels of TXNIP and NLRP3 in three kinds of breast cancer cell lines and HMEC cell line. MDA-MB231 cancer cells were divided into blank control group (normal culture without any treatment), TXNIP overexpression group (Ad-TXNIP group, transfected with adenovirus vector carrying TXNIP overexpression sequence), Ad-TXNIP negative control group (Ad-eGFP1 group, transfected of empty adenovirus vector without TXNIP overexpression sequence), NLRP3 overexpression group (Ad-NLRP3 group, transfected with adenovirus vector containing NLRP3 overexpression sequence), TXNIP and NLRP3 overexpression co-transfection group (Ad-TXNIP+Ad-NLRP3 group, co-transfection of adenovirus vector carrying TXNIP and NLRP3 overexpression sequence), TXNIP overexpression and Ad-NLRP3 negative control (Ad-eGFP2) co-transfection group (Ad-TXNIP+Ad-eGFP2 group,co-transfection of adenovirus vector carrying TXNIP overexpression sequence and empty adenovirus without NLRP3 overexpression sequence). After 24 hours of transfection and culture, CCK-8 method was used to detect the MDA-MB231 cells proliferation. Transwell chamber method was used to detect MDA-MB231 cells migration and invasion. Nude mice tumorigenicity test was used to detect the tumorigenicity of the MDA-MB231 cells in vivo. Western blot was used to detect the expressions of TXNIP, NLRP3, proliferation marker protein (Ki-67), caspase-1, vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-18 and caspase-1 precursor protein (pro-caspase-1) in the MDA-MB231 cells.ResultsCompared with the adjacent tissues, the relative expression level of TXNIP decreased (P<0.05) and the relative expression level of NLRP3 increased (P<0.05) in breast cancer tissues. Compared with normal breast epithelial cell line (HMEC cell line), the relative expression levels of TXNIP in MDA-MB231, MCF-7 and SKBR3 breast cancer cell lines were decreased (P<0.05), and the relative expression levels of NLRP3 were increased (P<0.05). Compared with the blank control group, the relative expression levels of TXNIP, NLRP3, IL-1β, IL-18, pro-caspase-1 and caspase-1 were increased (P<0.05), the relative expression levels of Ki-67 and VEGF, the proliferation activity, invasion and migration ability of MDA-MB231 cells and tumor weight were decreased (P<0.05) in the Ad-TXNIP group and the Ad-NLRP3 group. Compared with the Ad-TXNIP group and the Ad-NLRP3 group, the relative expression levels of TXNIP, NLRP3, IL-1β, IL-18, pro-caspase-1 and caspase-1 were further increased (P<0.05), the relative expression levels of Ki-67 and VEGF, the proliferation activity, invasion and migration ability of MDA-MB231 cells and tumor weight were further decreased (P<0.05) in the Ad-TXNIP+Ad-NLRP3 group.ConclusionsIn breast cancer tissues and breast cancer cell lines, TXNIP is low expression and NLRP3 is high expression. They can interact with each other to promote pyroptosis and inhibit the proliferation, invasion and migration of breast cancer cells.
ObjectiveTo detect the expression of Krüppel like factor 8 (KLF8) in breast cancer tissues and cells and to explore the clinical significance of KLF8.Methods① The Oncomine database was used to analyze the differential expression of KLF8 mRNA in the breast cancer tissues. The Kaplan-Meier Plotter database was used to analyze the relationship between KLF8 mRNA expression and prognosis (relapse free survival, overall survival, post-progression survival, and distant metastasis-free survival) of patients with breast cancer. ② The quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the KLF8 expression levels in the 16 clinical patients with breast cancer and 7 breast cancer cell lines (MDA-MB-231, MCF-12A, Hs-578T, MCF-7, BT-474, MDA-MB-453, ZR-75-30) and normal breast epithelial cell lines MCF-10A, and the immunofluorescence was used to further detect the localization of KLF8 expression in the 2 breast cancer cell lines with higher KLF8 expression level. ③ The immunohistochemistry was used to detect the expression of KLF8 protein in 135 cases of breast cancer tissue microarrays, and the relationships between KLF8 protein expression and clinicopathologic characteristics or overall survival were analyzed.Results① The Oncomine database showed that KLF8 mRNA expression in the breast cancer tissues was higher than that in the normal breast tissues (P<0.001). The median KLF8 mRNA expression level was taken as the cut-off point for high or low KLF8 expression. The results of Kaplan-Meier Plotter data analysis showed that the prognosis (relapse free survival, overall survival, postprogression survival, and distant metastasis-free survival) of patients with low KLF8 mRNA expression were better than those of patients with high KLF8 mRNA expression (P<0.05). ② The results of qRT-PCR and Western blot all showed that the KLF8 mRNA and protein expression levels in the breast cancer tissues were higher than those in the adjacent normal tissues (P=0.002, P<0.001). In addition, the Western blot results showed that the expression of KLF8 protein in the 7 breast cancer cell lines was higher than that in the normal breast epithelial cell lines MCF-10A respectively, and KLF8 protein mainly expressed in the cytoplasm of breast cancer cells and highly expressed in the nuclear of a few cells. ③ There were 63 cases of high KLF8 expression and 72 cases of low KLF8 expression by the immunohistochemical analysis of 135 patients with breast cancer tissue microarray (the H-score of the immunohistochemical test results was 75 as the cut-off point, H-score >75 was the high KLF8 expression and H-score ≤75 was the low KLF8 expression), the differences of statuses of estrogen receptor (ER) and progesterone receptor (PR) between the patient with high KLF8 expression and low KLF8 expression were significant (P<0.05). The Kaplan-Meier survival curve analysis showed that the prognosis of patients with high KLF8 expression was worse than that of patients with low KLF8 expression (P=0.002). The univariate analysis showed that the TNM stage, statuses of ER and PR, and KLF8 expression were related to the prognosis of patients with breast cancer (P<0.05), further multivariate Cox proportional hazards regression analysis indicated that the later stage of TNM and high KLF8 expression were the independent risk factors (P<0.05).ConclusionsThe results of this study suggest that KLF8 highly expresses in both breast cancer tissues and breast cancer cells, which is related to the statuses of ER and PR and prognosis of patients with breast cancer. KLF8 might be involved in the progression of breast cancer as an oncogenic gene, or it might provide a new direction for prognosis judgment and molecular targeted therapy of breast cancer.
ObjectiveTo summarize the progress of the researches about nano-carbon tattoo in targeted lymph node dissection of breast cancer. MethodThe relevant studies on the application of nano-carbon tattoo to target lymph nodes in the breast cancer at home and abroad were searched and the feasibility and shortcomings of this method were summarized. ResultFrom the studies reported, the nano-carbon tattoo method had a high detection rate (64.0%–100%) and coincidence rate (55.0%–100%), as well as a lower false negative rate (0.0%–9.1%) in the labeling of breast cancer targeted lymph nodes. ConclusionsThe nano-carbon tattoo method is a useful, simple, and safe in the labeling of targeted lymph nodes in breast cancer. But the specific implementation scheme of this method, such as the optimal labeling dosage, the number of labeled lymph nodes, and the improvement of patients’ quality of life are still unclear, which still needs more large-scale prospective research to verify.
Objective To study the risk factors for contralateral breast cancer (CBC) in women after regular treatment of the primary breast cancer. Methods Between January 1997 to December 2002, the clinical data of 340 breast cancer patients at our institution were retrospectively analyzed. In all the patients a detailed analysis was carried out with respect to age, operation type, radiation therapy technique and dose, the use of chemotherapy or hormone therapy, and other clinicopathologic characteristics. The KaplanMeier method was used to estimate the actuarial rate of CBC. The Cox proportional hazard regression model was used to estimate the relative risk factors of CBC. Results Fourteen cases were diagnosed to be CBC, thus overall incidence of CBC was 4.1%. Ten-year CBC incidence (2.7%) was higher than 5-year incidence of CBC (1.4%). Univariate analysis showed that the risk factors of CBC at 5-year and 10-year included: ≤45 years old, medullary carcinoma, family history of breast cancer and being taken without endocrine therapy (P＜0.05), while chemotherapy and radiotherapy were not risk factors of CBC (P＞0.05). Mutivariate analysis showed that ≤ 45 years old and being internal breast radiotherapy were independent risk factors of CBC at 5-year and 10-year (P＜0.05). Conclusions CBC may occur in these primary breast cancer patients with age ≤45 years old, medullary carcinoma, family history of breast cancer. In order to reduce the incidence of CBC, endocrine therapy rather than internal breast radiotherapy should be performed in early breast cancer patients.
ObjectiveTo investigate effect of resection of primary tumors on overall survival in patients with stage Ⅳ breast cancer.MethodsThe related literatures on the treatment of stage Ⅳ breast cancer in the PubMed, Medline, Cochrane Library, Embase, CNKI, Wanfang Data, CBM, VIP, etc. were comprehensively searched. Two authors independently screened the literatures and extracted data, including the overall survival, progression-free survival and tumor characteristics. The meta analysis was performed using RevMan 5.3 software and SPSS 21.0.ResultsA total of 21 articles were included in this study, including 17 retrospective cohort studies and 4 randomized controlled studies. A total of 5 250 patients with stage Ⅳ breast cancer were included, of which 2 686 patients underwent the local tumor resection+systemic therapy (operation group) and 2 564 patients only received the systemic therapy (non-operation group). The results of meta-analysis showed that the overall survival of the operation group was significantly better than that of the non-operation group [HR=0.64, 95%CI (0.59, 0.69), P<0.000 01], the result of subgroup analysis in the retrospective cohort studies [HR=0.60, 95%CI (0.55, 0.65), P<0.000 01] was consistent with this. However the disease-free survival had no statistical significance [HR=0.43, 95%CI (0.17, 1.11), P=0.08]. The clinicopathologic features of the two groups were further analyzed showed that the patients in the operation group were younger (P<0.05), and the proportions of the patients with T2 stage or below, bone metastasis, ER negative, radiotherapy, or metastatic lymph nodes less than 3 were higher (P<0.05) as compared with the non-operation group.ConclusionsLocal resection of primary tumors in patients with stage Ⅳ breast cancer can improve overall survival. Individualized treatment should be carried out.
ObjectiveTo understand the current research status of conservative mastectomy with breast reconstruction for breast cancer, so as to provide a reference for surgeons and patients with breast cancer to choose surgical method. MethodThe recently domestic and foreign literature on the research of conservative mastectomy with breast reconstruction for breast cancer was reviewed and summarized. ResultsAt present, conservative mastectomy mainly included nipple sparing mastectomy, skin sparing mastectomy, and skin reduction mastectomy. All three surgical methods were safe and effective in the treatment of breast cancer, and the complications could be controlled. When combined with breast reconstruction, the better cosmetic effect could be obtained, and the postoperative satisfaction and quality of life of patients were markedly improved. ConclusionsAfter comprehensively preoperative evaluation for patients with breast cancer, conservative mastectomy provides a treatment choice for them. After conservative mastectomy, individualized reconstruction scheme is formulated according to size and sagging degree of breast, as well as individual expectations of patients, which can obtain a higher quality of life while treating diseases for patients with breast cancer.
Objective To evaluate the association between fibroblast growth factor receptor 2 (FGFR2) rs2981582 polymorphism and the risk of breast cancer in Chinese population. Methods PubMed, Embase, Cochrane Library, Chinese Science and Technology Academic Journal, Chinese Biomedical Literature Database, Chinese Journal Full-Text Database, and Wanfang Database were searched to identify relevant articles that investigated the association of FGFR2 rs2981582 polymorphism with breast cancer risk from their inception to March 2018. A meta-analysis was performed by using the Stata 12.0 software. Results A total of 11 case-control studies were included in the present meta-analysis, including 5 921 breast cancer cases and 5 909 healthy controls. The pooled results indicated that, there was significant association between FGFR2 rs2981582 polymorphism and susceptibility of breast cancer in Chinese population under allele model ［C vs. T: OR=1.07, 95% CI was (1.01, 1.14), P=0.027］, heterozygote model ［CC vs. CT: OR=1.12, 95% CI was (1.01, 1.24), P=0.026］, homozygous model ［CC vs. TT: OR=1.19, 95% CI was (1.05, 1.34), P=0.005］, dominant model ［CC vs. CT+TT: OR=1.10, 95% CI was (1.00, 1.21), P=0.040］, and recessive model ［TT vs. CC+CT: OR=1.19, 95% CI was (1.10, 1.30), P<0.001］. Conclusion FGFR2 rs2981582 polymorphism was associated with the risk of breast cancer in Chinese population.
ObjectiveTo compare the prognosis of neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC) in patients with T1-2N1-2M0 luminal breast cancer, and to analyze the factors affecting the prognosis. MethodsPatients with luminal breast cancer who met the inclusion criteria and had complete follow-up data from January 2014 to December 2019 were retrospectively collected. Patients received either neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC), both based on anthracycline-containing regimens. Kaplan-Meier analysis was performed to estimate survival, and Cox proportional hazards regression was used to identify risk factors affecting 5-year cumulative overall survival rate. The significance level was set at α=0.05. ResultsA total of 206 patients (99 receiving NAC and 107 receiving AC) who met the inclusion criteria were enrolled. The cohort comprised 101 patients with luminal A (57 AC, 44 NAC) and 105 with luminal B (50 AC, 55 NAC). At a median follow-up of 72.5 months, no significant difference in the 5-year cumulative overall survival rate was observed between AC and NAC patients (89.7% vs. 88.9%, P=0.571); However, the 5-year cumulative disease-free survival rate was significantly higher in the AC group as compared with the NAC group (85.0% vs. 73.5%, P<0.001). Subgroup analysis demonstrated that no significant differences in the 5-year cumulative overall survival rates between AC and NAC patients within either luminal A (94.7% vs. 86.4%, P=0.727) or luminal B (84.0% vs. 89.3%, P=0.864). However, for patients with luminal A, the 5-year cumulative disease-free survival rate was significantly higher in the AC subgroup than in the NAC subgroup (93.0% vs. 77.3%, P<0.001). In contrast, no significant difference in the 5-year cumulative disease-free survival rate between AC and NAC patients was observed in patients with luminal B (74.0% vs. 71.4%, P=0.201). Multivariate analysis using the Cox proportional hazards model identified the following independent risk factors for lower 5-year cumulative overall survival rate in patients with T1-2N1-2M0 luminal breast cancer: N2 stage [HR (95%CI)=2.290 (1.249, 4.196)], lymphovascular invasion [HR (95%CI)=2.181 (1.182, 4.026)], omission of endocrine therapy [HR (95%CI)=6.013 (2.590, 13.965)], and absence of pathological complete response after NAC [HR (95%CI)=2.403 (1.284, 4.496)]. ConclusionsThe results of this study suggest that patients with T1-2N1-2M0 luminal breast cancer can achieve higher disease-free survival from AC. But it is still necessary to comprehensively consider the patient’s condition such as lymph node metastasis, vascular cancer thrombus to formulate an individualized treatment plan to increase the overall survival rate of patients.