Objective To systematically review the efficacy and safety of immune checkpoint inhibitors combined with chemotherapy in the treatment of triple-negative breast cancer. Methods The PubMed, Cochrane Library, Embase, Web of Science, CNKI, WanFang Data and VIP databases were searched for randomised controlled trials (RCTs) of immune checkpoint inhibitors combined with chemotherapy versus chemotherapy alone for triple-negative breast cancer from inception to April 1, 2024. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.4 software. Results A total of 13 RCTs involving 5 416 patients were included. The results of meta-analysis showed that the pathologic complete response rate (pCR) (OR=2.09, 95%CI 1.37 to 3.19, P<0.01), progression-free survival (PFS) (HR=0.75, 95%CI 0.67 to 0.83, P<0.01) and overall survival (OS) (HR=0.87, 95%CI 0.79 to 0.96, P<0.01) were significantly better than those in the control group. The results of subgroup analysis showed that there were statistically significant differences in PFS (P<0.01) and OS (P=0.02) between PD-L1-positive and PD-L1-negative patients, but there was no statistically significant difference in pCR between PD-L1-positive patients and PD-L1-negative patients (P=0.36). There was a statistically significant difference in pCR between node-positive patients and node-negative patients (P=0.03). There was no statistically significant difference in pCR between patients treated with PD-1 inhibitors and PD-L1 inhibitors (P=0.32); and there was no significant difference in PFS (P=0.19) or OS (P=0.99) between patients treated with PD-1 inhibitors and PD-L1 inhibitors. Compared with those in the control group, the incidences of serious adverse events (RR=1.36, 95%CI 1.09 to 1.70, P<0.01) and immune-related adverse events (RR=2.98, 95%CI 1.66 to 5.35, P<0.01) were higher in the experimental group, and the common immune-related adverse events were hypothyroidism and hyperthyroidism.Conclusion The existing evidence shows that immune checkpoint inhibitors combined with chemotherapy are more effective than chemotherapy alone in the treatment of triple-negative breast cancer, and the combination therapy has a higher incidence of adverse reactions. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.
ObjectiveTo compare clinicopathologic characteristics and prognosis between HER2-low and HER2-negative patients with stage T1 and T2 triple-negative breast cancer (TNBC). MethodsThe patients with stage T1 and T2 TNBC treated at the Affiliated Hospital of Southwest Medical University from June 2019 to June 2021 were retrospectively collected. The clinicopathologic features were analyzed using two-sided Chi-square test. Multivariate binary logistic regression identified risk factors for 3-year postoperative recurrence/metastasis. Kaplan-Meier survival curves was used to compare 3-year disease-free survival (DFS) between the TNBC patients with HER2-low and HER2-negative. The statistical significance was defined as α=0.05. ResultsA total of 126 patients with stage T1 and T2 TNBC were enrolled, 63 were HER2-negative and 63 HER2-low. Compared with HER2-negative patients, HER2-low patients demonstrated significantly higher proportions of: Age ≥50 years old, postmenopausal status, lymphovascular invasion (P<0.05). HER2 expression level and axillary lymph node metastasis were the independent risk factors for 3-year postoperative recurrence/metastasis in the patients with stage T1 and T2 TNBC (P<0.05). The patients with HER2-low expressing demonstrated significantly inferior 3-year DFS compared to patients with HER2-negative (χ2=7.741, P=0.005). ConclusionsFindings of this study suggest that among patients with stage T1 and T2 TNBC, HER2-low expression is associated with advanced age (≥50 years), menopausal status, and lymphovascular invasion. It may serve as an indicator of a distinct biologic subgroup or unfavorable pathologic characteristics. Patients with stage T1 and T2 TNBC who have HER2-low expression and positive axillary lymph node metastasis require close monitoring for recurrence/metastasis within 3 years postoperatively.
Objective To explore the expressions of androgen （AR） and Stathmin in triple negative breast cancer （TNBC） and analyze the correlation between these expressions and clinicopathologic features. Methods Eighty-three patients who were diagnosed as TNBC and met the inclusion criteria from 2005 to 2009 in the Sichuan Provincial People’s Hospital were collected retrospectively. The expressions of AR and Stathmin in the TNBC tissues by using the method of EnVision immunohistochemistry. The correlation between AR or Stathmin expression and age， tumor size， lymph node status， or histological grade was analyzed by Spearman test. Results The AR and Stathmin positive expression rates in the patients with TNBC were 37.3% （31/83） and 98.8% （82/83）， respectively. The AR expression was positively correlated with age（rs=0.302， P=0.006）and pathological grade （rs=0.225， P=0.041）， but was not correlated with tumor size or lymph node status. The Stathmin expression was not correlated with age， tumor size， lymph node status， or pathological grade （P＞0.05） . Conclusions The AR expression is correlated with the age or pathological grade but Stathmin expression was all not correlated with the clinicopathologic features. AR or Stathmin as a prognosis indicator in patients with TNBC are needed to more research.
ObjectiveTo investigate the relationship between the expression of IL-8 protein in triple negative breast cancer (TNBC) and clinicopathological features and survival prognosis.MethodsThe expression of IL-8 protein in 80 cases of TNBC was detected by immunohistochemical staining, and the relationship between the expression of IL-8 protein and clinicopathological features and prognosis of TNBC patients was analyzed by χ2 test, log-rank test, and Cox proportional hazards regression.ResultsIn 80 TNBC patients, the high expression of IL-8 protein accounted for 22.5% (18/80). The expression level of IL-8 protein in TNBC tumor tissue was correlated with T stage, clinical stage, Ki-67 expression, WHO grade and lymph node metastasis (P<0.05). However, it was not related to age, menopausal status, pathological type of tumor and whether they had received neoadjuvant chemotherapy (P>0.05). The results of log-rank analysis showed that the disease-free survival rate (DFS) of high expression group of IL-8 protein was poor than that of low expression group of IL-8 protein (P<0.05). Multivariate Cox proportional hazards regression analysis showed that the expression of IL-8 protein was an independent factor affecting the survival and prognosis of TNBC patients [HR=1.180, 95%CI (1.001, 1.391), P=0.049]. The prognosis of TNBC patients with high expression of IL-8 protein was poor.ConclusionThe expression level of IL-8 protein is an independent risk factor affecting the survival and prognosis of patients with TNBC.
ObjectiveTo investigate the expression of epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC) and its relation with clinicopathologic features. MethodsA computer search of PubMed, Web of Science, CNKI, Wanfang Data, and VIP databases were conducted to select clinical studies on EGFR expression in the TNBC according to the inclusion and exclusion criteria, and the search period was from database establishment to January 2022. Two researchers independently screened the literature, extracted the data, and evaluated the quality of the literature before conducting meta-analysis using RevMan 5.4 software. ResultsA total of 28 studies including 7 956 patients were included. The results of meta-analysis showed that the positive rate of EGFR expression in the TNBC patients was higher than that in the non-TNBC patients [OR=5.16, 95%CI (4.04, 6.58), P<0.000 01], and the proportions of patients with axillary lymph node metastasis [OR=3.11, 95%CI (1.56, 6.19), P=0.001] and with tumor diameter >2 cm [OR=2.09, 95%CI (1.18, 3.72), P=0.01] in the patients with EGFR positive were higher than those the patients with EGFR negative, no correlation was found that the proportion of patients with histological WHO classification 3 between the patients with EGFR positive expression and EGFR negative expression (P=0.07). ConclusionFrom the results of this meta-analysis, EGFR expression might be associated with the occurrence, development, and metastasis of patients with TNBC.
ObjectiveTo explore expression of epidermal growth factor receptor(EGFR) in triple-negative breast cancer(TNBC). Method The published articles about expression of EGFR in TNBC according to the inclusion and exclusion criteria from PubMed, Elsevier-Science Direct, and Web of Science databases were retrieved. The meta-analysis was performed with RevMan 5.2 software. ResultsA total of 8 articles were eligible for the meta-analysis. Among them, 1 006 patients in the TNBC group and 2 945 cases in the non-TNBC group. The result of meta-analysis showed that the positive rate of EGFR expression in the TNBC group was significantly higher than that in the non-TNBC group(OR=6.57, 95% CI 3.42-12.61, P < 0.000 01). The result of race subgroup analysis showed that the positive rate of EGFR expression of TNBC patients in Caucasian(OR=8.93, 95% CI 4.16-19.17, P < 0.000 01) or Xanthoderm(OR=2.79, 95% CI 0.99-7.89, P=0.05) was significantly increased as compared with non-TNBC patients. ConclusionThe positive rate of EGFR expression in TNBC patients is higher than that of non-TNBC patients, which might become an important marker of TNBC and an effective therapeutic target.
Objective To systematically evaluate expression of vascular endothelial growth factor (VEGF) protein in triple negative breast cancer (TNBC) and analyze its correlation between positive expression of VEGF protein and clinicopathologic features of patient with TNBC. Methods The published literatures relevant VEGF protein expression in TNBC and its relation to clinicopathologic features of patient with TNBC in China were retrieved by means of CNKI, Wanfang, VIP, China Biomedical, Chaoxing Medalink, PubMed databases, and other search tools. The literatures were independently filtered, extracted, and assessed by two reviewers according to the inclusion criteria and exclusion criteria. The meta-analysis was conducted by using RevMan 5.3 software. Results A total of 11 literatures were included and involved 1 838 patients (750 patients in the TNBC group and 1 088 patients in the non-TNBC group). The results of meta-nalysis showed that the positive expression of VEGF protein in the TNBC group was significantly higher than that in the non-TNBC group 〔OR=2.64, 95%CI (2.14, 3.26), P<0.000 01〕 , which was significantly increased in the TNBC patients with positive lymph node or stage Ⅲ–Ⅳ as compared with the negative lymph node or stage Ⅰ–Ⅱ 〔OR=0.30, 95% CI (0.14, 0.46), P=0.000 2; OR=0.43, 95% CI (0.29, 0.62), P<0.000 01〕 . However, the positive expression of VEGF protein was no associated with the age of patients with TNBC or tumor size (P>0.05). Conclusions VEGF highly expresses in TNBC and it is expected to be a new therapeutic target. Positive expression of VEGF protein is related to positive lymph node and late TNM stage, and it might be associated with prognosis of patient with TNBC.
ObjectiveTo sort out the key evidence-based data and recent advances in the systemic treatment of advanced triple-negative breast carcinoma (TNBC), to summarize the therapeutic strategies so as to provide guidance for clinical practice. MethodsThe key evidence and research progress on immune checkpoint inhibitors, antibody–drug conjugates (ADCs), poly ADP-ribose polymerase (PARP) inhibitors, anti-angiogenic agents, and novel microtubule inhibitors were summarized. ResultsThe treatment landscape for advanced TNBC has shifted from chemotherapy-centric approaches to biomarker-driven, stratified precision therapy. Based on programmed cell death ligand 1 (PD-L1) expression levels, immune therapy combined with chemotherapy is prioritized. For cases with germline breast cancer gene 1/2 (gBRCA1/2) mutations, PARP inhibitors are recommended. ADCs are suggested for second-line treatment, while novel microtubule inhibitors, either alone or in combination with anti-angiogenic agents, are preferred for later-line therapy to extend patient survival. ConclusionDynamic monitoring of molecular biomarkers such as PD-L1 and gBRCA, combined with sequential or combined "targeted–immunotherapy–ADC" regimens in a "chemotherapy-free" approach, has shown promise in improving overall survival in advanced TNBC.
ObjectiveTo summarize the research progress of Hippo signaling pathway in triple negative breast cancer (TNBC). MethodLiteratures about studies the role of Hippo signaling pathway in cancer stem cells, epithelial-mesenchymal transformation, tumorigenesis and development, distant metastasis, treatment resistance, and treatment strategies were retrieved. ResultsIn TNBC, overexpression of Yes-associated protein and PDZ-binding motif could promote the development of tumor stem cells, induce epithelial-mesenchymal transformation of TNBC cells, and promote tumor development, distant metastasis, and chemotherapy resistance. ConclusionHippo/Yes-associated protein axis plays an important role in carcinogenesis and progression of TNBC, and targeting Hippo signaling pathway might be a potential therapeutic target for TNBC.