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Single‐cell RNA sequencing (scRNA‐seq) is a novel technology that allows transcriptomic analyses of individual cells. During the past decade, scRNA‐seq sensitivity, accuracy, and efficiency have improved due to innovations including more sensitive, automated, and cost‐effective single‐cell isolation methods with higher throughput as well as ongoing technological development of scRNA‐seq protocols. Among the variety of current approaches with distinct features, researchers can choose the most suitable method to carry out their research. By profiling single cells in a complex population mix, scRNA‐seq presents great advantages over traditional sequencing methods in dissecting heterogeneity in cell populations hidden in bulk analysis and exploring rare cell types associated with tumorigenesis and metastasis. scRNA‐seq studies in recent years in the field of breast cancer research have clustered breast cancer cell populations with different molecular subtypes to identify distinct populations that may correlate with poor prognosis and drug resistance. The technology has also been used to explain tumor microenvironment heterogeneity by identifying distinct immune cell subsets that may be associated with immunosurveillance and are potential immunotherapy targets. Moreover, scRNA‐seq has diverse applications in breast cancer research besides exploring heterogeneity, including the analysis of cell‐cell communications, regulatory single‐cell states, immune cell distributions, and more. scRNA‐seq is also a promising tool that can facilitate individualized therapy due to its ability to define cell subsets with potential treatment targets. Although scRNA‐seq studies of therapeutic selection in breast cancer are currently limited, the application of this technology in this field is prospective. Joint efforts and original ideas are needed to better implement scRNA‐seq technologies in breast cancer research to pave the way for individualized treatment management. This review provides a brief introduction on the currently available scRNA‐seq approaches along with their corresponding strengths and weaknesses and may act as a reference for the selection of suitable methods for research. We also discuss the current applications of scRNA‐seq in breast cancer research for tumor heterogeneity analysis, individualized therapy, and the other research directions mentioned above by reviewing corresponding published studies. Finally, we discuss the limitations of current scRNA‐seq technologies and technical problems that remain to be overcome.

Background Characterizing the unique immune microenvironment of each tumor is of great importance for better predicting prognosis and guiding cancer immunotherapy. However, the unique features of the immune microenvironment of triple negative breast cancer (TNBC) compared with other subtypes of breast cancer remain elusive. Therefore, we aimed to depict and compare the immune landscape among TNBC, human epidermal growth factor receptor 2‐positive (HER2+) breast cancer, and luminal‐like breast cancer. Methods Single‐cell RNA sequencing (scRNA‐seq) was performed on CD45+ immune cells isolated from human normal breast tissues and primary breast tumors of various subtypes. By analyzing the scRNA‐seq data, immune cell clusters were identified and their proportions as well as transcriptome features were compared among TNBC, human HER2+ breast cancer, and luminal‐like breast cancer. Pseudotime and cell‐cell communication analyses were also conducted to characterize the immune microenvironment. Results ScRNA‐seq data of 117,958 immune cells were obtained and 31 immune clusters were identified. A unique immunosuppressive microenvironment in TNBC was decoded as compared to that in HER2+ or luminal‐like breast cancer, which was characterized by higher proportions of regulatory T cells (Tregs) and exhausted CD8+ T cells and accompanied by more abundant plasma cells. Tregs and exhausted CD8+T cells in TNBC exhibited increased immunosuppression signature and dysfunctional scores. Pseudotime analyses showed that B cells tended to differentiate to plasma cells in TNBC. Cell‐cell communication analyses indicated that these unique features are fostered by the diversified T cell‐B cell crosstalk in TNBC. Based on the T cell‐B cell crosstalk, a prognostic signature was established that could effectively predict the prognosis status for patients with TNBC. Additionally, it was found that TNBC had a higher proportion of cytotoxic natural killer (NK) cells, whereas HER2+ or luminal‐like breast cancer lost this feature, suggesting that HER2+ or luminal‐like breast cancer, but not TNBC, may benefit from NK‐based immunotherapy. Conclusions This study identified a distinct immune feature fostered by T cell‐B cell crosstalk in TNBC, which provides better prognostic information and effective therapeutic targets for breast cancer.

Breast cancer is a leading cause of cancer-related mortality, and the most prevalent malignant neoplasm amongst women worldwide. This study aimed to explore the role of FAM134B in breast cancer progression. The correlation between FAM134B expression and the prognosis of breast cancer patient was analyzed using the Kaplan-Meier Plotter database. qRT-PCR was used to quantify mRNA level, whereas western blotting was employed to detect th expression of FAM134B, autophagy-associated proteins, and endoplasmic reticulum (ER) stress related proteins. Cell proliferation was assessed via CCK-8 and colony formation assays. Cell apoptosis rate was measured by flow cytometry. Autophagosomes formation was observed under a transmission electron microscopy, and the expression of LC3 protein in cells was detected by immunofluorescence. The function of FAM134B was verified using a tumor xenograft model in nude mice. High expression of FAM134B in breast cancer patients was correlated with reduced overall survival and disease-free survival. Both FAM134B mRNA and protein levels were significantly higher in breast cancer cells than normal breast epithelial cells. Downregulation of FAM134B suppressed the proliferation of breast cancer cells and increased their apoptosis rates. Furthermore, silencing FAM134B triggered autophagy and ER stress in breast cancer. In nude mice, FAM134B knockdown also inhibited breast cancer progression and induced autophagy. Downregulation of FAM134B inhibited the development of breast cancer through inducing apoptosis, autophagy, and ER stress of breast cancer cells.

As one of the most common neoplasms globally, lung cancer (LC) is the leading cause of cancer-related mortality. Recurrence and metastasis negatively influencing therapeutic efficacy and overall survival demand new strategies in LC treatment. The advantages of TCM are increasingly highlighted. In this study, we obtained the major chemical components and their ratios in the aqueous extract of Taxus wallichiana var. chinensis (Pilg.) Florin (AETW) by UPLC-Q/TOF-MS/MS detection. The CCK-8 assay revealed that AETW could selectively inhibit the growth of A549 and HCC827 cells in a dose-dependent manner with little effect on normal human lung cells. Moreover, both in vitro and in vivo experiments showed that AETW was able to suppress the capacities of cell migration and invasion and downregulate the EMT and the JAK/STAT3 signaling pathway. To further probe into the molecular mechanism, the overexpression of STAT3 was performed into LC cells with AETW treatment, which counteracted the inhibitory effect on malignant behaviors of A549 and HCC827 cells with the decline in the expressions of p-JAK and p-STAT3. Taken together, we propose that AETW may inhibit the proliferation and metastasis by inactivating the JAK/STAT3 axis.

Endocrine therapy is the backbone therapy in estrogen receptor α (ER)-positive breast cancer, and tamoxifen resistance is a great challenge for endocrine therapy. Tamoxifen-resistant and sensitive samples from the international public repository, the Gene Expression Omnibus (GEO) database, were used to identify therapeutic biomarkers associated with tamoxifen resistance. In this study, integrated analysis was used to identify tamoxifen resistance-associated genes. Differentially expressed genes (DEGs) were identified. Gene ontology and pathway analysis were then analyzed. Weighted correlation network analysis (WGCNA) was performed to find modules correlated with tamoxifen resistance. Protein-protein interaction (PPI) network was used to find hub genes. Genes of prognostic significance were further validated in another GEO dataset and cohort from Shanghai Ruijin Hospital using RT-PCR. A total of 441 genes were down-regulated and 123 genes were up-regulated in tamoxifen-resistant samples. Those up-regulated genes were mostly enriched in the cell cycle pathway. Then, WGCNA was performed, and the brown module was correlated with tamoxifen resistance. An overlap of 81 genes was identified between differentially expressed genes (DEGs) and genes in the brown module. These genes were also enriched in the cell cycle. Twelve hub genes were identified using PPI network, which were involved in the mitosis phase of the cell cycle. Finally, 10 of these 12 genes were validated to be up-regulated in tamoxifen-resistant patients and were associated with poor prognosis in ER-positive patients. Our study suggested mitosis-related genes are mainly involved in tamoxifen resistance, and high expression of these genes could predict poor prognosis of patients receiving tamoxifen. These genes may be potential targets to improve efficacy of endocrine therapy in breast cancer, and inhibitors targeted these genes could be used in endocrine-resistant patients.

In recent years, endoscopic nipple-sparing mastectomy (ENM) has been applied in breast cancer treatment, whereas conventional open mastectomy (COM) remains widely adopted in clinical practice. The data about the oncological outcomes of ENM vs. COM was rare, especially the multicenter data. This multicenter retrospective cohort study enrolled 2,314 early breast cancer patients diagnosed with stage 0-III, and treated with either ENM or COM from September 1st, 2021 to January 30th, 2025 at three institutions. After exclusions, the final cohort consisted of 1,722 patients, of whom 136 were in the ENM group and 1,586 in the conventional group. Demographic data, clinicopathological features, and oncological outcomes were collected and analyzed. Propensity score matching (PSM) was performed to minimize selection bias and balance confounders. Before PSM, the patients in ENM group were significant different from COM group in age, menopausal status, hormone receptor status, HER2 status and molecular subtypes. After PSM, the final analysis cohort comprised 136 patients in the ENM group and 408 patients in the COM group. The median follow-up time was 22 months. No significant differences were observed between the two groups in any of the oncological outcome parameters: local recurrence-free survival between COM and ENM groups (97.8% vs. 97.8%; HR, 0.63; 95%CI, 0.14-2.90; P = 0.50); regional recurrence-free survival between COM and ENM groups (98.8% vs. 99.3%; HR, 1.24; 95%CI, 0.17-9.22; P = 0.84); distant metastasis-free survival between COM and ENM groups(97.3% vs. 98.5%; HR, 1.70; 95%CI, 0.47-6.11; P = 0.48); disease free survival between COM and ENM groups(94.9% vs. 96.3%; HR, 1.24; 95%CI, 0.50-3.10; P = 0.66); overall survival between COM and ENM groups(99.3% vs. 99.3%; HR, 0.76; 95%CI, 0.07-8.72; P = 0.81). In this multicenter cohort study, ENM group showed no different oncological outcomes from COM group. ENM could be used as a viable alternative to COM for eligible breast cancer patients.

PurposeDuctal carcinoma in situ (DCIS) is widely recognized as the precursor of invasive ductal carcinoma (IDC). We aimed to analyze the clinicopathological characteristics and clinical outcomes of coexisting DCIS component in IDC and its clinical significance according to molecular subtypes.MethodsData from 3001 patients with IDC (79.4%) and IDC/DCIS (20.6%) who underwent surgery from January 2009 to June 2016 were retrospectively assessed. The clinical outcomes of IDC with coexistent DCIS in different molecular subtypes were evaluated.ResultsIDC/DCIS patients were more likely to be younger (P < 0.001), had low tumor grade (P = 0.001), had less lymph node involvement (P = 0.038) and received more mastectomy (P = 0.002) than IDC patients. In the comparison of molecular subtype prevalence, IDC/DCIS patients were more frequently presented with luminal B/HER2 positive (12.5% vs 11.0%, P < 0.001) and HER2 positive subtypes (20.9% vs 9.8%, P < 0.001). The 5-year disease-free survival (DFS, 90.9% vs 87.5%, P = 0.021) and 5-year overall survival (OS 96.1% vs 94.0%, P = 0.018) were significantly improved in IDC/DCIS patients compared to IDC patients. In multivariate analysis, the presence of coexisting DCIS (P = 0.048), tumor size (P < 0.001), lymph node status (P < 0.001), lymphovascular invasion (P = 0.007) and molecular subtypes (P < 0.001) were independent prognostic factors for DFS. Furthermore, coexistence of DCIS component in IDC significantly improved DFS in HER2 positive (94.8% vs 78.5%, P = 0.003), but had no association in luminal and triple negative subtypes.ConclusionsIDC with coexisting DCIS was associated with improved prognosis. Patients with IDC/DCIS presented with more HER2 positive expression and might improve DFS in HER2 positive breast cancer.

The study aimed to evaluate the risk factors for the morbidity and prognosis of lung metastases (LM) in patients with newly diagnosed ovarian cancer (OC), and further explore the important role of marital status. Based on the Surveillance, Epidemiology, and End Results (SEER) dataset, OC patients from 2010 and 2019 were retrospectively analyzed. Logistic regression analysis and Kaplan-Meier method were applied to evaluate the vital factors of incidence and survival outcome in LM population. Cox regression analysis was performed to identify risk factors for the prognosis of OC patients with LM. The predictive potential was showed by two established nomograms and examined by the concordance index (C-index), calibration curves, the area under the curve (AUC), decision curve analyses (DCAs) and clinical impact curves (CICs). There are 25,202 eligible OC patients were enrolled in the study, the morbidity of LM at 5.61%. Multivariable logistic regression models illustrated that chemotherapy ( ), surgical treatment of bilateral or more areas ( ), T stage ( ), N1 stage ( ), bone metastasis ( ), brain metastasis ( ) and liver metastasis ( ) were all significantly connected with LM in OC. Multivariable Cox regression analyses illustrated that unmarried, radiotherapy, elder people and positive cancer antigen 125 (CA-125) were significantly associated with shorter survival time, while chemotherapy made contributions to improve survival. Our study found that marital relationships promoted LM and was associated with the better prognosis, while unmarried patients had the opposite results. With the further development of our research, the cross-action of social, economic and psychological factors together determined the great impact of marital status on the morbidity and prognosis of OC patients combined with LM. Finally, the stability of the models was proved by internal verification. The population-based cohort study provides references for guiding clinical screening and individualized treatment of OC patients with LM. Under the influence of society and economy, marital status is closely related to the morbidity and prognosis of OC, which can be an important direction to explore the risk of OC lung metastasis in the future.

Colorectal cancer (CRC) is considered to be closely associated with alteration of intestinal microorganisms. The purpose of present study was to investigate the distribution of gut microbiota in the distinction of microbiota dysbiosis between two disease syndromes called Zheng-Qi-Kui-Xu(ZQKX) and Xie-Du-Yong-Sheng (XDYS). First, From February 2019 to June 2019, CRC patients presenting to the oncology department of Zhejiang Province Hospital of TCM who met the established inclusion and exclusion criteria were enrolled in this prospective study. After fresh stool specimens of healthy volunteers and CRC patients with ZQKX or XDYS syndorme were collected, 16S rRNA gene amplification and sequencing could be used to identify the diversity and abundance of gut microbiota among groups. The results demonstrated that the composition of the microbiota in general control group was superior to those in experimental groups. At the phylum level, a significantly increased abundance of Bacteroides was observed in healthy volunteers. At the class level, Erysipelothrix decreased while Lactobacillaceae showed increased abundance in the ZQKX group compared to healthy controls. At the family level, Prevotella Shan and Collins decreased while Streptococcus significantly increased in patients with XDYS syndrome compared to healthy subjects. Five differential taxa were identified between ZQKX and XDYS syndromes. We suggest that the gut microbiota contributes to the distinction between the two TCM syndromes of CRC, which can be used as a biological basis of TCM syndrome differentiation treatment in CRC.

Background: In adjuvant settings, epirubicin and cyclophosphamide (EC) and docetaxel and cyclophosphamide (TC) are both optional chemotherapy regimens for lymph node-negative, hormone receptor (HR)-positive, human epidermal receptor 2 (HER2)-negative breast cancer patients. Neutropenia is one of the most common adverse events (AEs) of these regimens. The rate of grade 3–4 neutropenia varies in different studies, and direct comparisons of safety profiles between EC and TC are lacking. Method: ELEGANT (NCT02549677) is a prospective, randomized, open-label, noninferior hematological safety trial. Eligible patients with lymph node-negative HR+/HER2-tumors (1:1) were randomly assigned to received four cycles of EC (90/600 mg/m2) or TC (75/600 mg/m2) every three weeks as adjuvant chemotherapy. The primary endpoint was the incidence of grade 3 or 4 neutropenia defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 on an intention-to-treat basis. Noninferiority was defined as an upper 95% CI less than a noninferiority margin of 15%. Results: In the intention-to-treat population, 140 and 135 patients were randomized into the EC and TC arms, respectively. For the primary endpoint, the rate of grade 3 or 4 neutropenia is 50.71% (95% CI: 42.18%, 59.21%) in the EC arm and 48.15% (95% CI: 39.53%, 56.87%) in the TC arm (95%CI risk difference: −0.100, 0.151), showing the noninferiority of the EC arm. For secondary endpoints, the rate of all-grade anemia is higher in the EC arm (EC 42.86% versus TC 22.96%, p = 0.0007), and more patients suffer from nausea/vomiting, hair loss, and nail changes (p < 0.01) in the EC arm. No statistically different disease-free survival was observed between the two arms (p = 0.13). Conclusion: EC is not inferior to TC in the rate of grade 3 or 4 neutropenia, but more other AEs were observed in the EC group.