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The use of trastuzumab emtansine (T‐DM1) has revealed significant efficacy in HER2‐positive metastatic breast cancer (MBC). However, optimal therapeutic strategies following T‐DM1 failure remain a subject of debate in clinical practice. In this multicenter, retrospective, real‐world study, we sought to examine the effectiveness and safety of tyrosine kinase inhibitors (TKIs) as a therapeutic strategy in HER2‐positive MBC who developed T‐DM1 resistance. Between September 2018 and December 2022, 66 patients were enrolled. The median progression‐free survival of TKIs‐based therapy was 10.1 months (95% CI, 4.7–15.6). Objective response rate and clinical benefit rate were 18.2 and 66.7%, respectively. TKIs‐based therapy demonstrated better effectiveness in patients who had previously derived benefit from T‐DM1 and featured acquired resistance to trastuzumab. The most common adverse events were diarrhea (36, 54.5%), hand‐foot syndrome (31, 47.0%), and leucopenia (30, 45.5%). In conclusion, TKIs‐based therapy showed promising effectiveness and safety in HER2‐positive MBC patients after T‐DM1 failure. [ABSTRACT FROM AUTHOR]

Simple Summary: Palbociclib is one of the preferred treatments for hormone-receptor-positive, HER2-negative metastatic breast cancer in women; its effectiveness and safety in the Chinese real-world population require further investigation. Our study aimed to identify the clinical outcomes of patients who received palbociclib in combination with endocrine therapy (ET) in China. The effectiveness of palbociclib plus ET in treating metastatic breast cancer was confirmed in 397 Chinese patients across eight clinical sites. The regimens were well tolerated by both the general and elderly groups. However, some factors were identified as potential hindrances to the therapy's benefits, including higher Ki-67 expression, primary resistance to ETs, liver metastases, more metastatic sites, later line of therapy, and the use of fulvestrant instead of aromatase inhibitors. Palbociclib is useful for treatment of metastasis breast cancer, and our study may provide a basis for further research. Background: Palbociclib has been approved for marketing in China. However, its effectiveness, safety, and latent variables in the Chinese population require further investigation. Methods: Information was retrieved from 397 patients with metastatic breast cancer (mBC) who received at least two cycles of palbociclib plus endocrine therapy (PAL plus ET) at eight clinical sites in China. The patients' demographic characteristics, treatment patterns, and adverse events (AEs) were analyzed. Results: The objective response rate (ORR) and clinical benefit rate (CBR) for PAL plus ET were 28.97% and 66.25%, respectively. The median PFS was 14.2 months in the whole population. In addition to protein Ki-67 status and sensitivity to ETs, no liver metastases, fewer metastatic sites, an earlier line of therapy, and treatment combined with AI instead of FUL were also considered as independent prognostic factors for PAL treatment. Administration of PAL was generally well tolerated in patients with hormone-receptor-positive and human-epidermal-growth-factor-receptor-2-negative (HR+/HER2−) advanced breast cancer (ABC). The therapy was safe in the elderly population, which is consistent with the outcomes of the whole population and previous reports. Conclusions: In this most widely distributed study in China to date, palbociclib combined with ET proved its effectiveness for HR+/HER2− ABC treatment, and adverse events were manageable. Here, we identified some independent prognosis factors, but the mechanism by which these factors influence effectiveness requires further verification. [ABSTRACT FROM AUTHOR]

Simple Summary: There are limited treatments for patients with HER2-negative breast cancer, especially for patients with metastatic breast cancer. This study aimed to observe the efficacy and safety of low-dose apatinib combined with chemotherapy in real-world clinical diagnosis and treatment of HER2-negative metastatic breast cancer. A total of 128 patients were treated with 250 mg apatinib, and we observed the median progression-free survival (PFS) and overall survival (OS) were 4.7 months and 15.3 months, respectively. This observation also indicated that the breast cancer susceptibility gene (BRCA) mutation predicted a better response to apatinib and that combination of immunotherapy or paclitaxel-platinum regimens might be an optimal treatment option. Importantly, a lower dose of apatinib showed mild side effects that improved the patients' life quality. Treatment options for human epidermal growth factor receptor (HER2)-negative breast cancer patients are limited in comparison to the HER2-positive patients, particularly for metastatic breast cancer patients. Apatinib is a small-molecule tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor 2 (VEGFR-2). Here, we reported the apatinib-based therapy data in HER2-negative metastatic breast cancer. Apatinib was taken at a dose of 250 mg orally once per day and combined with standard chemotherapy regimens. The PFS and OS of 128 patients were 4.7 months and 15.3 months, respectively. The objective response rate (ORR) and the disease control rate (DCR) were 22.7% and 80.5%, respectively. Patients with breast cancer susceptibility gene (BRCA) mutations were found to have a longer PFS and OS. Moreover, combination immunotherapy or paclitaxel-platinum regimens shared an improved response to other regimens. Most of the adverse effects (hypertension, anaemia, and hand-foot syndrome) were grade 1 to 2. Metastatic breast cancer patients could benefit from apatinib therapy at a low dosage, and the adverse effects are mild in real-world clinical practice. Furthermore, BRCA may be a putative biomarker for apatinib in HER2-negative breast cancer. Immunotherapy or paclitaxel-platinum regimens may be recommended to combine with apatinib therapy. [ABSTRACT FROM AUTHOR]

PURPOSE: To examine the impact of a clinical decision support system (CDSS) on breast cancer treatment decisions and adherence to National Comprehensive Cancer Center (NCCN) guidelines. PATIENTS AND METHODS: A cross-sectional observational study was conducted involving 1,977 patients at high risk for recurrent or metastatic breast cancer from the Chinese Society of Clinical Oncology. Ten oncologists provided blinded treatment recommendations for an average of 198 patients before and after viewing therapeutic options offered by the CDSS. Univariable and bivariable analyses of treatment changes were performed, and multivariable logistic regressions were estimated to examine the effects of physician experience (years), patient age, and receptor subtype/TNM stage. RESULTS: Treatment decisions changed in 105 (5%) of 1,977 patients and were concentrated in those with hormone receptor (HR)–positive disease or stage IV disease in the first-line therapy setting (73% and 58%, respectively). Logistic regressions showed that decision changes were more likely in those with HR-positive cancer (odds ratio [OR], 1.58; P <.05) and less likely in those with stage IIA (OR, 0.29; P <.05) or IIIA cancer (OR, 0.08; P <.01). Reasons cited for changes included consideration of the CDSS therapeutic options (63% of patients), patient factors highlighted by the tool (23%), and the decision logic of the tool (13%). Patient age and oncologist experience were not associated with decision changes. Adherence to NCCN treatment guidelines increased slightly after using the CDSS (0.5%; P =.003). CONCLUSION: Use of an artificial intelligence–based CDSS had a significant impact on treatment decisions and NCCN guideline adherence in HR-positive breast cancers. Although cases of stage IV disease in the first-line therapy setting were also more likely to be changed, the effect was not statistically significant (P =.22). Additional research on decision impact, patient-physician communication, learning, and clinical outcomes is needed to establish the overall value of the technology. [ABSTRACT FROM AUTHOR]

Lapatinib, targeting the human epidermal growth factor receptor family members HER1 and HER2, has been approved by the US Food and Drug Administration for use in metastatic HER2-positive breast cancer. However, resistance to lapatinib remains a common challenge to HER2-positive metastatic breast cancer. Until now, the molecular mechanisms of acquired resistance to lapatinib (ALR) have remained unclear. With no definite biomarkers currently known, we aimed to screen for key biomarkers in ALR. In this research, we identified 55 differentially expressed genes (DEGs, 20 upregulated, 35 downregulated) through bioinformatic analysis using microarray datasets GSE16179, GSE38376, and GSE51889 from the Gene Expression Omnibus (GEO) database. The related gene function was explored using the Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed with the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape. The functional enrichment of the DEGs was analyzed, including negative regulation of the B cell apoptotic process, DNA replication, solute:proton symporter activity, synthesis, and degradation of ketone bodies, and metal sequestration by antimicrobial proteins. Analysis of seven hub genes revealed their concentration mainly in DNA replication and cell cycle. Survival analysis revealed that MCM10 and SPC24 may be related with poor prognosis in patients with ALR. Meanwhile, the prediction model of lapatinib sensitivity was constructed, and emerging role of the model was further analyzed using several webtools. In conclusion, hub genes are involved in the complex mechanisms underlying ALR in breast cancer and provide favorable support for treatment of ALR in future. [ABSTRACT FROM AUTHOR]

OSW‐1 is a natural compound extracted from the bulbs of Ornithogalum saundersiae in 1992. It has been shown strong antitumor activities in various cancer cells. However, the effects of OSW‐1 on tumor growth and metastasis in breast cancer are still poorly understood. In our research, we showed that OSW‐1 had a strong anticancer effect on breast cancer cells, but lower toxicity to normal cells. Accordingly, it also revealed significant inhibition of tumor growth by OSW‐1 in xenograft model. In addition, we performed Annexin V/PI‐labeled flow cytometric assay and TUNEL assay and showed that OSW‐1 inhibited tumor growth by inducing apoptosis. Furthermore, we carried out transwell assays and found that OSW‐1 significantly repressed the migratory and invasive capabilities of triple‐negative breast cancer (TNBC) cells via mediating epithelial‐mesenchymal transition. Besides, OSW‐1 also could inhibit metastasis in an orthotopic model and resulted in a longer survival compared with control group. Finally, we performed RNA‐sequencing and cellular functions to investigate the molecular mechanism of how OSW‐1 inhibits TNBC, and identified NFATc2 may as a pivotal factor for OSW‐1‐mediated effects on cell death, tumor growth, invasion, and migration. [ABSTRACT FROM AUTHOR]

Background: The efficacy and safety of lapatinib plus capecitabine (LC or LX) versus trastuzumab plus chemotherapy in patients with HER-positive metastatic breast cancer who are resistant to trastuzumab is unknown.Methods: We retrospectively analyzed data from breast cancer patients who began treatment with regimens of lapatinib plus capecitabine (LC or LX) or trastuzumab beyond progression (TBP) at eight hospitals between May 2010 and October 2017.Results: Among 554 patients who had developed resistance to trastuzumab, the median PFS (progression free survival) was 6.77 months in the LX group compared with 5.6 months in the TBP group (hazard ratio 0.804; 95% CI, 0.67 to 0.96; P = 0.019). The central nervous system progression rate during treatment was 5.9% in the LX group and 12.5% in the TBP group (P = 0.018).Conclusion: The combination of lapatinib and capecitabine showed a prolonged PFS relative to TBP in patients who had progressed on trastuzumab. [ABSTRACT FROM AUTHOR]

Background: Previous case reports have shown the promising antitumor activity of everolimus in solid tumors containing molecular aberrations in PI3K/ATK/mTOR pathway, however, whether it is effective in patients with breast cancer remains unknown. Therefore, we conducted this retrospective cohort study to compare the efficacy of molecularly matched targeted therapy with everolimus to conventional therapy in refractory breast cancer patients harboring PI3K/ATK/mTOR pathway activating mutations. Methods: Refractory metastatic breast cancer patients who have received molecular screening using next‐generation sequencing (NGS) between September 8, 2015 and October 30, 2017 in two sites were screened for this study. The primary outcome was progression‐free survival (PFS). The secondary outcomes were overall response rate (ORR), disease control rate (DCR), and safety profile. Results: A total of 78 patients were screened for analysis, amongst all, 52 (66.7%) had at least one gene mutation in PI3K/AKT/mTOR pathway. The most common mutation fell in PIK3CA (76.9%, 40/52) with a mutational prevalence of 51.3%. Of the 32 patients who were eligible for efficacy analysis, patients in the everolimus group (n = 19) exhibited shorter PFS than those in the conventional group (n = 13) (median, 1.9 vs 6.1 months; HR, 3.6; 95% CI, 1.48‐8.81; P = .0005). ORR was 15.4% (2/13) in the everolimus group and 23.1% (3/13) in the conventional group (P = 1.000), and DCR was 30.8% (4/13) and 100% (13/13) for each group, respectively (P = .000). The incidence of grade 3‐5 adverse events was relatively higher in the conventional group (38.5%, 5/13) than that in the everolimus group (26.3%, 5/19). Conclusions: Our findings suggested that everolimus might not be effective for cancer patients harboring mutations in PI3K/ATK/mTOR pathway and physicians should be cautious about its off‐label use in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Despite therapeutic advances in HER2-positive metastatic breast cancer, resistance to trastuzumab inevitably develops. In the PHOEBE study, we aimed to assess the efficacy and safety of pyrotinib (an irreversible pan-HER inhibitor) plus capecitabine after previous trastuzumab.Methods: This is an open-label, randomised, controlled, phase 3 trial done at 29 hospitals in China. Patients with pathologically confirmed HER2-positive metastatic breast cancer, aged 18-70 years, who had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had been previously treated with trastuzumab and taxanes were randomly assigned (1:1) to receive oral pyrotinib 400 mg or lapatinib 1250 mg once daily plus oral capecitabine 1000 mg/m2 twice daily on days 1-14 of each 21-day cycle. Randomisation was done via a centralised interactive web-response system with a block size of four or six and stratified by hormone receptor status and previous lines of chemotherapy for metastatic disease. The primary endpoint was progression-free survival according to masked independent central review. Efficacy and safety were assessed in all patients who received at least one dose of the study drugs. Results presented here are from a prespecified interim analysis. This study is registered with ClinicalTrials.gov, NCT03080805.Findings: Between July 31, 2017, and Oct 30, 2018, 267 patients were enrolled and randomly assigned. 134 patients received pyrotinib plus capecitabine and 132 received lapatinib plus capecitabine. At data cutoff of the interim analysis on March 31, 2019, median progression-free survival was significantly longer with pyrotinib plus capecitabine (12·5 months [95% CI 9·7-not reached]) than with lapatinib plus capecitabine (6·8 months [5·4-8·1]; hazard ratio 0·39 [95% CI 0·27-0·56]; one-sided p<0·0001). The most common grade 3 or worse adverse events were diarrhoea (41 [31%] in the pyrotinib group vs 11 [8%] in the lapatinib group) and hand-foot syndrome (22 [16%] vs 20 [15%]). Serious adverse events were reported for 14 (10%) patients in the pyrotinib group and 11 (8%) patients in the lapatinib group. No treatment-related deaths were reported in the pyrotinib group and one sudden death in the lapatinib group was considered treatment related.Interpretation: Pyrotinib plus capecitabine significantly improved progression-free survival compared with that for lapatinib plus capecitabine, with manageable toxicity, and can be considered an alternative treatment option for patients with HER2-positive metastatic breast cancer after trastuzumab and chemotherapy.Funding: Jiangsu Hengrui Medicine and National Key R&D Program of China.Translations: For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

The emergence of antibody-drug conjugates (ADCs) targeting trophoblast cell-surface antigen-2 (Trop-2) has reshaped the therapeutic landscape of advanced breast cancer. Accurate profiling of the Trop-2 status of tumor cells can facilitate the identification of patients who will benefit from Trop-2-targeting therapy; however limited analytical method has hindered this process. In this study, we have proposed a specific and sensitive biosensor for visual tracking of the Trop-2 status of breast cancer cells based on tetrahedral DNA nanostructure (TDN)-decorated Fe-based metal-organic framework nanoparticles (TDN-PCN-222 (Fe)). In the design, a dual-aptamer-assisted biomimetic capture strategy shows high capture efficiency while maintaining the viability and original phenotype of captured cells, ensuring the accurate profiling of the Trop-2 status. Meanwhile, by using the high intrinsic peroxidase activity and excellent targeting ability of Trop-2-specific aptamer-linked TDN-PCN-222 (Fe), specific detection of Trop-2-positive tumor cells can be achieved with a limit of detection (LOD) of 10 cells/mL, and the Trop-2 status of tumor cells can be visually tracked. Moreover, the proposed biosensor has been successfully used for tracking the Trop-2 status of tumor cells in breast cancer tissues, suggesting that our method has great promise for clinical applications. • Colorimetric sensor is fabricated to track Trop-2 status of breast cancer cells. • Specific and sensitive detection of Trop-2-positive tumor cells can be achieved. • The capture strategy can maintain the viability and phenotype of captured cells. • Visual profiling of Trop-2 status of tumor cells in cancer tissues is possible. [ABSTRACT FROM AUTHOR]