According to the classification presented by Lehmann BD (2016), triple-negative breast cancer (TNBC) is a heterogeneous group of malignant tumors with four specific subtypes: basal-like (subtype 1 and subtype 2), mesenchymal, and luminal androgen receptor (LAR) subtypes. The basal-like subtypes of carcinomas predominate in this group, accounting for up to 80% of all cases. Despite the significantly lower proportions of mesenchymal and LAR variants in the group of breast carcinomas with a TNBC profile, such tumors are characterized by aggressive biological behavior. To this end, the LAR subtype is of particular interest, since the literature on such tumors presents different and even contradictory data concerning the disease course and prognosis. This review is devoted to the analysis of the relevant literature, reflecting the main results of studies on the molecular properties and clinical features of the disease course of LAR-type TNBC carcinomas.
Carcinoma ; Humans ; Receptors, Androgen/genetics* ; Triple Negative Breast Neoplasms/pathology*

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with a heterogeneous genetic profile. Chemotherapy exhibits substantial activity in a small subset of these patients. Drug resistance is inevitable. Major progress has been made in the genetic analysis of TNBC to identify novel targets and increase the precision of therapeutic intervention. Such progress has translated into major advances in treatment strategies, including modified chemotherapy approaches, immune checkpoint inhibitors, and targeted therapeutic drugs. All of these strategies have been evaluated in clinical trials. Nevertheless, patient selection remains a considerable challenge in clinical practice.
Humans ; Immunotherapy ; Molecular Targeted Therapy ; Triple Negative Breast Neoplasms/genetics*

Biomarkers, Tumor/genetics* ; Breast Neoplasms/genetics* ; Female ; Humans ; Receptor, ErbB-2/genetics* ; Triple Negative Breast Neoplasms/genetics*

Objective: To investigate the expression of programmed death ligand-1 (PD-L1, SP142) and PD-L1 (22C3) in triple-negative breast cancer (TNBC), and analyze their correlation with the clinicopathological factors and prognosis. Methods: The clinicopathologic data of 259 patients with TNBC treated in Cancer Hospital from August 2010 to December 2013 were collected. Whole section of surgical tissue samples were collected to conduct PD-L1 (SP142) and PD-L1 (22C3) immunohistochemical (IHC) staining. The PD-L1 expression in tumor cells and tumor infiltrating immune cells were visually assessed respectively, the relationship between PD-L1 expression and clinicopathologic characterizes were analyzed. Univariable and multivariable Cox proportional hazards regression models were used to test the correlations between PD-L1 expression and disease-free survival (DFS) and overall survival (OS). Results: The positive rates of SP142 (immune cell score, ICs≥1%) and 22C3 (combined positive score, CPS≥1) were 42.1%(109/259) and 41.3%(107/259) in TNBC tissues, respectively, with a total coincidence rate of 82.3%. The Kappa value of positive expression cases was 0.571 and the distribution difference of SP142 and 22C3 positive expression cases was statistically significant (P<0.001). The PD-L1 positive patients were less likely to have vascular invasion (P<0.05), but with higher histological grade and Ki-67 proliferation index (P<0.05). The recurrence/metastasis cases(8) of the patients with positive PD-L1 (SP142) was significantly lower than that of patients with negative PD-L1(SP142, 27, P=0.016). The positive expression of PD-L1 (SP142) patients were longer DFS (P=0.019). The OS of patients with positive PD-L1 (SP142) were longer than those with negative PD-L1 (SP142), but without significance (P=0.116). The positive expression of PD-L1 (22C3) was marginally associated with DFS and OS of patients (P>0.05). Conclusions: The expression of PD-L1 (22C3) is different from that of PD-L1 (SP142) in TNBC, and the two antibodies can't be interchangeable for each other in clinical tests. PD-L1 (SP142) status is an independent prognostic factor of DFS in TNBC. The DFS is significantly prolonged in patients with positive expression of PD-L1 (SP142).
B7-H1 Antigen/genetics* ; Humans ; Immunohistochemistry ; Prognosis ; Triple Negative Breast Neoplasms/pathology*

Breast cancer is a malignant tumor that seriously endangers women's lives. The prognosis of breast cancer patients differs among molecular types. Compared with other subtypes, triple-negative breast cancer (TNBC) has been a research hotspot in recent years because of its high degree of malignancy, strong invasiveness, rapid progression, easy of recurrence, distant metastasis, poor prognosis, and high mortality. Many studies have found that long non-coding RNA (lncRNA) plays an important role in the occurrence, proliferation, migration, recurrence, chemotherapy resistance, and other characteristics of TNBC. Some lncRNAs are expected to become biomarkers in the diagnosis and prognosis of TNBC, and even new targets for its treatment. Based on a PubMed literature search, this review summarizes the progress in research on lncRNAs in TNBC and discusses their roles in TNBC diagnosis, prognosis, and chemotherapy with the hope of providing help for future research.
Humans ; Female ; Triple Negative Breast Neoplasms/genetics* ; RNA, Long Noncoding/genetics* ; Biomarkers, Tumor/genetics* ; Gene Expression Regulation, Neoplastic

Humans ; Triple Negative Breast Neoplasms/genetics* ; MicroRNAs/genetics* ; Oncogenes ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Cell Movement

Triple negative breast cancer (TNBC) is prone to recurrence and metastasis, which is the subtype of poorest prognosis. Chemotherapy is the main treatment, although there is lack of effective adjuvant chemotherapy regimens. The unsatisfactory efficacy of chemotherapy has been a bottleneck in improving the outcome of TNBC. Platinum compounds act directly on DNA to kill tumor cells, and they have a stronger killing effect on tumor cells carrying DNA damage repair (DDR) defects, which is an important entry point to improve the efficacy of TNBC. Biomarkers for predicting the efficacy of platinum drugs in TNBC treatment have always been a hot topic. The DDR pathway contains a large number of related genes, and recent studies have shown that deficiencies in the DDR pathway may be associated with the efficacy of platinum drugs, which is expected to be a biomarker for predicting the efficacy of platinum drugs in breast cancer treatment.
Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; DNA Damage ; DNA Repair ; Humans ; Pharmaceutical Preparations ; Platinum/therapeutic use* ; Platinum Compounds/therapeutic use* ; Triple Negative Breast Neoplasms/genetics*

Precision oncology aims to offer the most appropriate treatments to cancer patients mainly based on their individual genetic information. Genomics has provided numerous valuable data on driver mutations and risk loci; however, it remains a formidable challenge to transform these data into therapeutic agents. Transcriptomics describes the multifarious expression patterns of both mRNAs and non-coding RNAs (ncRNAs), which facilitates the deciphering of genomic codes. In this review, we take breast cancer as an example to demonstrate the applications of these rich RNA resources in precision medicine exploration. These include the use of mRNA profiles in triple-negative breast cancer (TNBC) subtyping to inform corresponding candidate targeted therapies; current advancements and achievements of high-throughput RNA interference (RNAi) screening technologies in breast cancer; and microRNAs as functional signatures for defining cell identities and regulating the biological activities of breast cancer cells. We summarize the benefits of transcriptomic analyses in breast cancer management and propose that unscrambling the core signaling networks of cancer may be an important task of multiple-omic data integration for precision oncology.
Female ; Gene Expression Profiling ; Genomics ; Humans ; MicroRNAs ; metabolism ; Precision Medicine ; RNA Interference ; RNA, Messenger ; metabolism ; Triple Negative Breast Neoplasms ; classification ; genetics ; metabolism ; therapy

Objective: To investigate the germline mutation status of related genes in breast cancer patients and high-risk individuals by next-generation sequencing. To analyze the correlations between homologous recombination repair (HR) pathway gene mutation status and clinicopathological characteristics of breast cancer patients. To supplement the database of breast cancer related gene mutations in Chinese population. Methods: This study is a cross-sectional study. From October 2020 to September 2021, whole blood samples were collected from 350 breast cancer patients and 49 high-risk individuals, admitted to Peking University People's Hospital and accepted genetic testing voluntarily. Germline mutations in 32 breast cancer related genes were detected by NGS. The clinicopathological characteristics, including age at the onset, family history, unilateral/bilateral tumor, Luminal typing (Luminal A subtype, Luminal B subtype, HER2-enriched subtype and triple negative breast cancer), tumor size and metastasis, were analyzed, and the correlations between HR pathway gene mutation status and clinicopathological characteristics were analyzed by Chi-squared test and Fisher's exact probability test. Results: Among 350 breast cancer patients, 64 (18.3%) cases carried gene pathogenic mutations (including pathogenic and likely pathogenic mutations), including 47 (13.4%) in BRCA1/2, 16 (4.6%) in non-BRCA1/2 genes, 1 (0.3%) in BRCA2 and FANCL. Among 49 high-risk individuals, 7 (14.3%) cases carried gene pathogenic mutations, including 6 (12.3%) in BRCA1/2 and 1 (2%) in ATM genes. BRCA1/2 pathogenic mutations were associated with age at the onset (18%, 8.7%, χ²=6.346, P=0.012), and the BRCA1/2 pathogenic mutation frequency was higher in patients diagnosed at age ≤45 years. HR pathway gene mutations (including pathogenic, likely pathogenic and uncertain significance mutations) were correlated with unilateral/bilateral tumor (49.5%, 68.4%, χ²=4.841, P=0.028) and Luminal typing (45.7%, 62.2%, 32%, 60%, χ²=12.004, P=0.007), and the HR mutation frequencies were higher in patients with bilateral tumor, Luminal B breast cancer and triple negative breast cancer (TNBC). Conclusion: The BRCA1/2 pathogenic mutation frequency in high-risk individuals is similar to that in breast cancer patients, and BRCA1/2 testing is helpful to guide breast cancer screening and prevention in high-risk individuals. Patients with early onset breast cancer, bilateral breast cancer, Luminal B breast cancer and TNBC have higher mutation frequencies of HR pathway genes, and HR pathway genes testing should be conducted as soon as possible to provide laboratory evidence for diagnosis, treatment, prognosis and risk evaluation of breast cancer.
BRCA1 Protein/genetics* ; BRCA2 Protein/genetics* ; Breast Neoplasms/pathology* ; Cross-Sectional Studies ; Female ; Genetic Predisposition to Disease ; Germ-Line Mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Middle Aged ; Mutation ; Recombinational DNA Repair ; Triple Negative Breast Neoplasms/pathology*

To examine the expressions of epithelial cell adhesion molecule (EpCAM), vimentin and N-cadherin in breast cancer and its molecular subtypes, and to explore the correlation among them.
 Methods: The expressions of EpCAM, vimentin and N-cadherin were detected by immunohistochemistry in 835 patients with breast cancer, and their correlations with clinical pathological features and prognosis were analyzed.
 Results: The expression rates of EpCAM, vimentin and N-cadherin in the patients were 53.4%, 11.4% and 9.7% respectively, which were increased with the increase in tumor size, histological grade, lymph node size, tumor node stage of metastases classification, estrogen receptor and progesterone receptor levels (all P<0.05). The positive expression rates for EpCAM protein in luminal A, luminal B (HER2-), luminal B (HER2+), HER2 overexpression and triple-negative subtypes were 19.2%, 73.0%, 48.9%, 72.2%, and 62.1% respectively; for vimentin were 3.9%, 11.4%, 14.1%, 11.1%, and 20.5% respectively; for N-cadherin were 7.0%, 5.7%, 12.0%, 12.2% and 17.4% respectively, with statistical difference (all P<0.05). EpCAM expression was positively correlated with vimentin and N-cadherin in patients with breast cancer and triple-negative breast cancer.
 Conclusion: EpCAM is overexpressed in triple-negative subtype of breast cancer and it is associated with epithelial-mesenchymal transition markers, which might be related to breast cancer progression and metastasis.
Antigens, CD ; Biomarkers, Tumor ; Breast Neoplasms ; chemistry ; classification ; genetics ; Cadherins ; Epithelial Cell Adhesion Molecule ; Epithelial-Mesenchymal Transition ; Female ; Humans ; Immunohistochemistry ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2 ; Receptors, Estrogen ; Receptors, Progesterone ; Triple Negative Breast Neoplasms ; Vimentin