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Background: Triple-negative breast cancer (TNBC) is a life-threatening subtype of breast cancer with limited treatment options. Therefore, this network meta-analysis (NMA) aimed to evaluate and compare the effect of various neoadjuvant chemotherapy (NCT) options on the long-term survival of patients with TNBC. Methods: PubMed, Embase, Medline, Cochrane Library, Web of Science, and major international conference databases were systematically searched for randomized controlled trials (RCTs) on the efficacy of various NCT options in patients with TNBC. Searches were performed from January 2000 to June 2023. Study heterogeneity was assessed using the I2 statistic. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate disease-free survival (DFS) and overall survival (OS). Odds ratios (ORs) and 95% CIs were used to evaluate the pathologic complete response (pCR). The primary outcome was DFS. Results: We conducted an NMA of 21 RCTs involving 8873 patients with TNBC. Our study defined the combination of anthracyclines and taxanes as the preferred treatment option. On this basis, the addition of any of the following new drugs is considered a new treatment option: bevacizumab (B), platinum (P), poly-ADP-ribose polymerase inhibitors (PARPi), and immune checkpoint inhibitor (ICI). Based on the surface under the cumulative ranking curve (SUCRA) values, the top three SUCRA area values of DFS were taxanes, anthracycline, and cyclophosphamide (TAC; 89.23%); CT (84.53%); and B (81.06%). The top three SUCRA area values of OS were CT (83.70%), TAC (62.02%), and B-containing regimens (60.06%). The top three SUCRA area values of pCR were B + P-containing regimens (82.7%), ICI + P-containing regimens (80.2%), and ICI-containing regimens (61.8%). Conclusions: This NMA showed that standard chemotherapy is a good choice with respect to long-term survival. Moreover, B associated with P-containing regimens is likely to be the optimal treatment option for neoadjuvant TNBC in terms of pCR. [ABSTRACT FROM AUTHOR]

• Breast cancer related differentially expressed genes were identified based on TCGA database and GTEx database. • The GIMAP family genes with relatively high diagnostic values for the patients of breast cancer were analyzed. • Immune infiltration of GIMAP family genes obtained, providing selectable targets for breast cancer treatment. Breast cancer is the most common malignancy threatening women's health worldwide. The GTPase IMAP family genes are proteins belonging to the immune-associated nucleotide subfamily of the GTP-binding superfamily and nucleotide-binding proteins. However, little is known about the role of different GTPase IMAP family genes in breast cancer. We obtained differential genes from the GEPIA and UALCAN databases and then used the Kaplan–Meier plotter, The Human Protein Atlas, NetworkAnalyst, STRING, and TIMER to analyze the prognostic value, protein expression, and immune cell infiltration of the GTPase IMAP family in patients with breast cancer. Among the GIMAP family genes, the expression levels of GIMAP1, GIMAP5, GIMAP6, GIMAP7, and GIMAP8 were significantly low in breast tumor tissues. In the overall population, patients with high expression of all genes of the GIMAP family had a significantly higher overall survival (OS), with the most significant increase correlated with the GIMAP2 gene (hazard ratio [HR] = 0.45, 95% confidence interval [CI], 0.34–0.59, P = 3.1e−09). However, patients with high expression of the GIMAP family genes in triple-negative breast cancer compared to those with low expression had a significant OS benefit, with the most pronounced benefit correlated with the GIMAP2 gene (HR = 0.37, 95% CI, 0.23–0.59, P = 1.4e−05). GIMAP7 and GIMAP8 were significantly upregulated in breast tumor tissues. The expression of genes in different GIMAP families was positively correlated with the infiltration and expression of six immune cell types (B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells). This study may provide novel insights into the selection of GIMAP family prognostic biomarkers for breast cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] • Question • Will the immunotherapy addition to chemotherapy for metastatic triple-negative breast cancer (mTNBC) compared with standalone chemotherapy increased clinical efficacy? • Findings • This meta-analysis of 4 randomized clinical trials with 3007 patients found that it significantly improved progression-free survival in mTNBC patients with programmed death ligand-1 (PD-L1) positive. • Meaning • This result may provide more options for the treatment of mTNBC patients with PD-L1 positive. One of the front treatment regimens used for metastatic triple-negative breast cancer (mTNBC) is treatment with programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) blockade combine with chemotherapy. However, the results of such studies have been controversial. A systematic searched of PubMed, Embase, Cochrane Library, and the proceedings of the last 5 years of several meetings until February 18, 2021. The primary endpoint was the progression-free survival (PFS) of PD-L1-positive patients treated with PD1/PD-L1 blockade plus chemotherapy compare with chemotherapy. Overall, 4 studies that included a total of 3007 mTNBC patients were analyzed in this meta-analysis. PFS was significantly improved in the PD1/PD-L1 blockade plus chemotherapy group compared with the chemotherapy group in PD-L1-positive mTNBC patients (hazard ratios, (HR), 0.69; 95% CI, 0.59–0.80; P <.001), also in intention-to-treat (ITT) population (HR, 0.82; 95% CI, 0.74–0.90; P <.001). However, no significant benefit in overall survival (OS) was observed regardless of PD-L1 status or ITT population. The immunotherapy plus chemotherapy has higher adverse events (AEs) compared with chemotherapy (all AEs, Odds ratios (ORs), 2.33; 95% CI, 1.50–3.62; P <.001; grade 3-5 AEs, OR, 1.27; 95% CI, 1.04–1.55; P =.019). This meta-analysis showed that the addition of PD1/PD-L1 blockade to chemotherapy improved PFS in PD-L1 positive mTNBC patients, also in the ITT population. However, no significant benefit in OS was observed in patients of PD-L1 positive or in the ITT population after adding PD1/PD-L1 blockade. We found a higher rate of AEs with the addition of PD1/PD-L1 blockers to chemotherapy. [ABSTRACT FROM AUTHOR]