Breast cancer (BC) is an important cause of cancer-related death in the world. As a subtype of BC with the worst prognosis, triple-negative breast cancer (TNBC) is a serious threat to human life and health. In recent years, there has been an increasing amount of research aimed at designing and developing nanomaterials for the diagnosis and treatment of TNBC. The purpose of this study was to comprehensively evaluate the current status and trend of the application of nanomaterials in TNBC through bibliometric analysis. Studies focusing on nanomaterials and cancer were searched from the Web of Science core collection (WOSCC) database, and relevant literature meeting the inclusion criteria was selected for inclusion in the study. VOSviewer and CiteSpace were used to perform bibliometric and visual analysis of the included publications. A total of 2338 studies were included. Annual publications have increased from 2010 to 2024. China, the United States and India were the leading countries in the field, accounting for 66.1%, 11.5% and 7.2% of publications, respectively. The Chinese Academy of Sciences and Li Yaping were the most influential institutions and authors, respectively. Journal of Controlled Release was considered the most productive journal. Cancer Research was considered to be the most co-cited journal. Drug delivery and anti-cancer mechanisms related to nanomaterials were considered to be the most widely studied aspects, and green synthesis and anti-cancer mechanisms were also recent research hotspots. In this study, the characteristics of publications were summarized, and the most influential countries, institutions, authors, journals, hot spots and trends in the application of nanomaterials in cancer were identified. These findings provide valuable insights into the current state and future direction of this dynamic field.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and leads to the poorest patient outcomes despite surgery and chemotherapy treatment. Exploring new molecular mechanisms of TNBC that could lead to the development of novel molecular targets are critically important for improving therapeutic options for treating TNBC.
We sought to identify novel therapeutic targets in TNBC by combining genomic and functional studies with lipidomic analysis, which included mechanistic studies to elucidate the pathways that tie lipid profile to critical cancer cell properties. Our studies were performed in a large panel of human breast cancer cell lines and patient samples.
Comprehensive lipid profiling revealed that phospholipid metabolism is reprogrammed in TNBC cells. We discovered that patatin-like phospholipase domain-containing lipase 8 (PNPLA8) is overexpressed in TNBC cell lines and tissues from breast cancer patients. Silencing of PNPLA8 disrupted phospholipid metabolic reprogramming in TNBC, particularly affecting the levels of phosphatidylglycerol (PG), phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and glycerophosphocholine (GPC). We showed that PNPLA8 is essential in regulating cell viability, migration and antioxidation in TNBC cells and promoted arachidonic acid and eicosanoid production, which in turn activated PI3K/Akt/Gsk3β and MAPK signaling.
Our study highlights PNPLA8 as key regulator of phospholipid metabolic reprogramming and malignant phenotypes in TNBC, which could be further developed as a novel molecular treatment target.

BACKGROUND: Breast cancer (BC) is a highly heterogeneous disease. Among the BC molecular subtypes, basal-like/triple-negative BC (TNBC) is characterized by a high propensity for relatively early metastases and a lack of available endocrine and targeted therapies. Therefore, this study aimed to discover potential signatures for predicting the immune response in early-stage basal-like/triple-negative BC.
METHODS: A total of 86 cases of early-stage TNBC from the TCGA and 459 cases of normal breast tissue from GTEx were enrolled and analyzed to screen out differentially expressed genes (DEGs). Then, the prognostic effect and tumor immune cell infiltration relationship with the basal-like-specific DEGs were also evaluated.
RESULTS: A total of 1556 DEGs, including 929 upregulated genes and 627 downregulated genes, were screened in early-stage basal-like BC. Two prognosis-associated DEGs, GAL and TTC36, were finally found to be basal-like BC specific. However, only GAL was significantly correlated with tumor immune-infiltrating cells, especially CD8+ T cells. The expressions of GAL and TTC36 were revalidated by using the GEO dataset.
CONCLUSIONS: GAL might be an immune signature for the response to immune checkpoint therapy in early basal-like/triple-negative BC.

OBJECTIVE: This study aimed to assess the efficacy and safety of various neoadjuvant regimens for patients diagnosed with early-stage or locally advanced triple-negative breast cancer (TNBC).
METHODS: Medline, EMBASE, Cochrane Library, and Web of Science were searched in May 2020 to identify randomized controlled trials (RCTs). Bayesian network meta-analysis (NMA) was performed (Registration: PROSPERO CRD42020223012).
RESULTS: A total of 35 RCTs involving 8,424 participants were reviewed, of which 22 RCTs with 5,203 patients were included in this NMA focusing on pathologic complete response (pCR). An anthracycline-taxane-based (AT) regimen combined with a platinum (ATPt) [odds ratio (OR) = 2.04, 95% credible interval (CrI): 1.69, 2.48] regimen, and a docetaxel regimen combined with a carboplatin (TCb; OR = 2.16, 95% CrI: 1.20, 3.91) regimen improved pCR beyond that with AT only. AT and ATPt combined with targeted therapy [including bevacizumab (Bev), veliparib, atezolizumab, or pembrolizumab] also improved pCR. Five RCTs included in this NMA reported serious adverse events (SAEs) or grade ≥ 3 AEs. TCb was associated with fewer grade ≥ 3 AEs than was AT (OR = 0.66, 95% CrI: 0.23, 1.72) alone. In contrast, ATPt, AT + Bev, ATPt + Bev, ATPt + veliparib, and ATPt + pembrolizumab were associated with more SAEs than was AT alone.
CONCLUSIONS: In patients with TNBC, platinum-based neoadjuvant regimens ATPt and TCb increase pCR beyond that with AT alone, but TCb appears to be better tolerated than either AT or ATPt. Platinum-based regimens combined with targeted therapies (Bev, PARPi, and PD-1/PD-L1 inhibitor) also improve the pCR rate beyond that with AT alone, but this benefit is accompanied by greater toxicity.

Objective: To observe the short-term efficacy and safety of apatinib in combination with dose-dense paclitaxel and carboplatin in locally advanced triple-negative breast cancer (TNBC) patients. Methods: From September 2018 to September 2019, 17 stage Ⅱ/Ⅲ TNBC patients were enrolled in this single arm, single center prospective phase Ⅱ study. They received neoadjuvant treatment of apatinib 250 mg per day, paclitaxel 175 mg/m(2) on 1(st) day and a dose of carboplatin according to the area under curve (AUC)=4 on 2(nd) day, every 14 days as a cycle. Results: By January 2020, 16 cases completed 4-7 cycles of apatinib treatment and 4-8 cycles of chemotherapy. The median cycles of apatinib treatment and chemotherapy were 5 cycles and 6 cycles, respectively. Two cases achieved complete responses (CR), 12 achieved partial responses (PR), 2 achieved stable diseases (SD) and no progressive disease was observed. The objective response rate (ORR) was 87.5%, disease control rate (DCR) was 100%. By January 2020, among 12 patients who received surgery, 8 achieved pathologic complete response (pCR, 66.7%). The grade Ⅲ/Ⅳ adverse events included: neutropenia, thrombocytopenia in 3 cases (18.8%) each, anemia, fatigue, arrhythmia and alanine aminotransferase (ALT) elevation in 1 case each. Apatinib was interrupted in 5 cases, and was discontinued in 3 cases; chemotherapy dosage was reduced in 1 case. Conclusion: Apatinib in combination with dose-dense paclitaxel and carboplatin neoadjuvant therapy are effective and well tolerated in locally advanced TNBC patients.
目的： 观察阿帕替尼联合紫杉醇和卡铂密集方案新辅助治疗三阴性乳腺癌(TNBC)的近期疗效及安全性。 方法： 采用单中心、单臂、前瞻性Ⅱ期临床研究，纳入Ⅱ～Ⅲ期TNBC患者17例。新辅助治疗方法：阿帕替尼250 mg，1次/d；紫杉醇175 mg/m(2)第1天；卡铂给药剂量按曲线下面积＝4计算，第2天；每14 d为1个周期。 结果： 16例患者纳入统计分析。16例患者完成阿帕替尼治疗的中位周期数为5个，化疗的中位周期数为6个。完全缓解2例，部分缓解12例，疾病稳定2例，客观缓解率为87.5%，疾病控制为100%。12例患者完成手术治疗，其中8例(66.7%)达病理完全缓解。Ⅲ～Ⅳ级不良反应为粒细胞下降和血小板下降各3例，贫血、疲乏、心律失常和丙氨酸氨基转移酶增高各1例。阿帕替尼中断治疗5例，永久停药3例，化疗减量1例。 结论： 阿帕替尼联合紫杉醇、卡铂密集方案新辅助化疗TNBC近期疗效较好，不良反应可控，未发生严重不良反应。.

UNASSIGNED: To compare the efficacy of platinum- and non-platinum-based regimens as first-line treatment for advanced triple-negative breast cancer (TNBC) and analyze the relationship between their efficacy and BRCA gene status.
UNASSIGNED: Retrospectively analyze clinical data of 220 patients diagnosed pathologically with advanced TNBC and treated at the Department of Breast Oncology, Peking University Cancer Hospital from 2013 to 2018 and evaluate the efficacy of chemotherapy. A total of 114 patients had BRCA1/2 gene tested by next generation sequencing (NGS) using peripheral blood, and we analyzed the correlation between their efficacy and BRCA1/2 gene status.
UNASSIGNED: Non-platinum-based chemotherapy (NPCT) was administered to 129 and platinum-based chemotherapy (PBCT) to 91 study patients. The clinical benefit rate (CBR) and median progression-free survival (PFS) were not statistically different between NPCT and PBCT groups. The median overall survival (OS) was 30.0 and 22.5 months for PBCT and NPCT group, respectively [P=0.090, hazard ratios (HR)=0.703]. BRCA status was assessed in 114 patients, 14 of whom had deleterious germline BRCA1/2 (gBRCA) mutations (seven in each group). In PBCT group, the CBR was 85.7% and 35.1% for patients with and without deleterious gBRCA mutations, respectively (P=0.039). The median PFS were 14.9 and 5.3 months and median OS were 26.5 and 15.5 months for patients with and without deleterious gBRCA mutations, respectively (P=0.001, P=0.161, respectively). Patients in PBCT group had significantly greater rates of grade 3-4 anemia (5.5%vs. 0%) and thrombocytopenia (8.8% vs. 0%), whereas palmar-plantar erythrodysesthesia (12.4% vs. 0%) and peripheral neuropathy (8.6% vs. 1.1%) occurred more frequently in NPCT group.
UNASSIGNED: Platinum-based regimens are more effective in patients with deleterious gBRCA mutations, but no difference in patients without BRCA gene mutations, so non-platinum is an option in patients without BRCA gene mutations considering the toxicity and side effect. And we recommend that patients with advanced TNBC should have BRCA gene test.

UNASSIGNED: Triple negative breast cancer (TNBC), as defined by ER, PR and HER2 negative expression in tumor, has limited treatment options beyond conventional chemotherapy. JS001, a humanized IgG4 antibody for PD-1, has demonstrated acceptable safety profile and preliminary anti-tumor activity in solid tumors.
UNASSIGNED: This phase I open-label study is designed to evaluate the safety, tolerability, and antitumor activity of JS001 in advanced TNBC patients who are refractory to standard systemic therapy. The study has a 3+3 dose escalation design with planned cohorts at 1, 3, and 10 mg/kg Q2W followed by a dose expansion cohort at 3 mg/kg. (Clinical Trial ID: NCT02838823).
UNASSIGNED: From August 04, 2016 to October 26, 2017, 20 heavily-pretreated advanced TNBC patients were enrolled into three dose cohorts (6 in 1 mg/kg, 8 in 3 mg/kg and 6 in 10 mg/kg). As of August 30, 2018, no DLT was observed and no MTD was reached. No AEs were grade 4 or 5. The most common treatment related AEs were all grade 1/2. Treatment related grade 3 AEs (15%) included 1 hyponatremia, 1 rash and 1 bronchospasm (infusion related reaction). Among 20 evaluable subjects, the ORR was 5%. One patient in 10 mg/kg group obtained PR, who was PD-L1 strong positive (>50%) in tumor biopsy, with treatment duration of 12.8 months as of data cutoff. As of follow-up on July 15, 2019, the patient continued PR with treatment duration of 24 months and still ongoing. Six patients achieved SD, for a DCR of 35%. The median PFS of all subjects was 1.8 months (95% CI, 1.4 to 4.6). 45% subjects are PD-L1 positive (≥1% cutoff), among whom a 11.1% ORR and a 22.2% DCR were observed.
UNASSIGNED: JS001 exhibited a favorable safety profile in advanced TNBC patients who are refractory to multi-line systemic therapy. JS001 also showed a moderate response in these TNBC patients who had limited treatment options.

BACKGROUND: Triple-negative breast cancer (TNBC) is associated with an aggressive phenotype and poor prognosis, and the lack of druggable markers leads to the unavailability of targeted therapies. Thus, there is an urgent need to identify potential targets for triple-negative breast cancer.
OBJECTIVE: In this study, we aimed to explore the expression of LAPTM4B and p27kip1 in triple-negative breast cancer, and its clinical significance.
METHODS: We analyzed the expression and association of LAPTM4B and p27kip1 in human breast cancer databases. To analyze the role of LAPTM4B in the aggressiveness of the human triple-negative breast cancer, the expressions of LAPTM4B were knocked down in MDA-MB-231 and HCC1187 cell lines. Then, cell proliferation, migration and apoptosis were assessed in vitro. Furthermore, the immunohistochemistry examinations of LAPTM4B and p27kip1 expression were performed using surgical specimens from 188 primary triple-negative breast cancer patients.
RESULTS: Through analyses of several independent breast cancer cohorts, we found the correlation of the LAPTM4B and p27kip1 expression. Remarkably, the knockdown of LAPTM4B restored p27kip1 expression and inhibited the aggressiveness of breast cancer cells. Meanwhile, the knockdown of p27kip1 relieved the suppression of cell migration. Consistent with the analyses of human breast cancer cohorts, the immunohistochemistry results showed that the expression levels of LAPTM4B and p27kip1 were correlated in 188 triple-negative breast cancer samples (p= 0.019). We also validated that the higher LAPTM4B expression, the lower p27kip1 expression (p= 0.0001), and the LAPTM4B+/p27kip1- subgroup (p< 0.0001) were poor prognostic indicators, as well as the higher histologic grade (p= 0.0001). In the multivariate Cox regression, p27kip1 expression was considered as an independent predictor of survival (p< 0.001).
CONCLUSIONS: The overexpression of LAPTM4B and the loss of p27kip1 expression are correlated. Meanwhile, the up-regulated expression of LAPTM4B together with the down-regulated expression of p27kip1 could classified a group of breast cancer patients with poor prognosis, consequently considered as a potentially prognostic marker and candidate target for therapeutic intervention of triple-negative breast cancer.

OBJECTIVE: To evaluate the incidence of cMET proto-oncogene aberration in a cohort of triple negative breast cancers using immunohistochemistry and fluorescence in situ hybridization (FISH) methods and correlated with patient outcome.
METHODS: One hundred and six female patients with diagnosis of triple negative invasive breast carcinoma at The University of Texas-M D Anderson Cancer Center from 1983 to 2009 were included in the study. Expression of cMET was assessed by IHC using rabbit monoclonal anti-total cMET antibody (SP44 from Ventana). Staining intensity was scored on a scale of 0, 1+, 2+ and 3+. cMET overexpression was defined as at least moderate membranous/cytoplasmic staining in ≥50% of tumor cells (score ≥ 2+). FISH analysis was performed using MET (7q31) specific probe (BAC clone RP11-95i20, Abbott Molecular Inc.) and the centromere probe (CEP7/D7Z1, Abbott Molecular Inc.) as internal control. cMET amplification was defined as gene copy numbers ≥4 per cell or cMET/CEP7 ratio ≥ 2. cMET status was tested for correlation using Fisher\'s exact test with other clinicopathological parameters. The Kaplan-Meier product limit method was used to estimate the survival outcomes. Cox proportional hazards models were fit to determine the association of cMET status by IHC, or by FISH, or by copy number with survival outcomes after adjustment for other patient and disease characteristics.
RESULTS: Medium follow up is 69.4 months (range 9-317 months). cMET was successfully evaluated by both IHC and FISH methods in ninety-six patients. There were 13 patients whose tumors overexpressed cMET was by IHC. Two patients had cMET amplification by FISH using definitive of cMET/CEP7 ratio of ≥2 and four patients had cMET copy number >4. Only one patient showed cMET/CEP7 ratio of 2.53 and one was positive for cMET overexpression by IHC. No significant association between cMET overexpression by IHC and by FISH using cut-off of with either cMET/CEP7 ratio of ≥2 or cMET copy number of >4 (P = 1.0). There was no significant correlation between the cMET overexpression and other clinicopathological characteristics, such as patient demographics, tumor grade, stage, or chemotherapy treatment history. cMET overexpression and gene amplification did not correlate with the prognosis of TNBC regarding OS or DFS.
CONCLUSIONS: MET amplification is a rare incidence in TNBCs. cMET overexpression is infrequent in TNBCs and may not be driven by gene amplification. Neither have significant prognostic value nor do they correlate with other clinicopathological characteristics in this TNBC cohort.

Background: Triple-negative breast cancer (TNBC) is a heterogeneous disease closely associated with epithelial-to-mesenchymal transition (EMT). This study aimed to investigate the role of EMT in metaplastic carcinoma. Methods: E-cadherin, Slug, Twist and Vimentin levels were detected by immunohistochemistry in 167 TNBC tumors, including 145 invasive carcinomas of no special type (ICONSTs), 14 spindle cell carcinomas (SpCCs) and 8 matrix-producing carcinomas (MPCs). Results: Nuclear Slug and Twist were more frequently detected in SpCC and MPC tumors than that in ICONST tumors (p<0.001). The rate of E-cadherin loss was much lower in the ICONST tumors than that in the SpCC and MPC tumors (p<0.001). Vimentin was expressed in all SpCC and MPC tumors. Furthermore, nuclear expression of Slug and Twist was positively associated with the cytoplasmic localization of Vimentin (p<0.001) and was inversely associated with membranous staining of E-cadherin (p<0.001). These trends were more apparent in the SpCC and MPC tumors than in the ICONST tumors. Follow-up data were available for 151 patients. The follow-up times ranged from 1 month to 11 years (mean: 74 m; median: 21 m). The median progression-free survival and overall survival times were 24 months (mean: 32 months) and 22 months (mean: 35 months), respectively. Tumor size, TNM stage and E-cadherin were found to be independent prognostic factors of TNBC. Conclusions: EMT may play an important role in TNBC, especially in MPC and SpCC. Further researches are needed to confirm this finding. The results of this study may facilitate the future development of targeted therapies based on alterations in the EMT and stem cell markers.