Disitamab vedotin (RC48-ADC), an antibody-drug conjugate (ADC), combines specific antibody disitamab with cytotoxicity monomethyl auristatin E to effectively target the human epidermal growth factor receptor 2 (HER2) protein on tumor cells for precise elimination. Recent studies have demonstrated that RC48-ADC offers therapeutic benefits for patients with HER2-positive and HER2-low-expression breast cancer (BC). However, a thorough exploration of its efficacy and safety in real-world settings for patients with metastatic breast cancer (mBC) is currently lacking. This retrospective, multicenter, real-world study included patients with mBC who received RC48-ADC from September 2021 to March 2024. These patients include HER2-positive BC and HER2-low-expression BC. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), restricted mean survival time, objective response rate (ORR), and disease control rate (DCR). Factors affecting efficacy and the occurrence of treatment-related adverse events (TRAE) were evaluated. The study included a cohort of 89 patients with mBC, with 48 of those being identified as HER2-positive. As of March 2024, 22 deaths were recorded, with an immature median OS. Total PFS varied from 1.0 to 31.2 months, with a median of 5.5 months (95% CI, 4.368-6.632). HER2-positive patients exhibited prolonged PFS compared with HER2-low-expression patients (6.6 months vs 4.1 months, P = .023). The overall ORR stood at 25.8% (95% CI, 0.178-0.358), with higher rates observed in HER2-positive patients compared with HER2-low-expression patients (31.3% vs 19.5%). Similarly, the overall DCR was 78.7% (95% CI, 0.691-0.859), with HER2-positive patients demonstrating superior DCR compared with HER2-low-expression patients (83.3% vs 73.2%). Notably, HER2 expression emerged as the primary determinant of RC48-ADC efficacy. The most prevalent TRAE among all patients included leukopenia (21.3%) and alopecia (20.2%). RC48-ADC showcases promising efficacy and manageable safety in patients with both HER2-positive and HER2-low-expression mBC.

Background: In previous clinical trials, pyrotinib has shown good antitumor activity and manageable toxicity in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). However, real-world data on pyrotinib remain limited. In this study, we reported the latest real-world data on the efficacy and safety of pyrotinib in HER2-positive MBC. Methods: This multicenter retrospective study included 337 HER2-positive MBC patients treated with pyrotinib between October 2016 and October 2024. We reported the analysis of the efficacy and safety of pyrotinib in HER2-positive MBC. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Results: As of April 1, 2025, the median follow-up duration was 42.6 months (range, 2.0-92.7). The median line of treatment was two. The median PFS was 15.3 months (95% CI, 12.9-17.6). By treatment line, the median PFS was 21.4 months (95% CI, 10.1-32.6) for first-line treatment, 14.8 months (95% CI, 11.4-18.1), and 10.9 months (95% CI, 8.1-13.7) for second-line and third-line or above treatment. The 3-year OS rate was 54.6% overall, with 63.2%, 61.1%, and 37.7% for first-line, second-line, and third-line or above treatment. The ORR, DCR, and CBR were 41.5%, 91.2%, and 80.0%. We further analyzed 57 patients with brain metastases (BM). The result showed that the median duration of response (DoR) and time to response (IQR) of radiotherapy-naïve ones were 12.6 months (95% CI, 6.8-18.4) and 1.7 months (95% CI, 1.3-2.2), respectively. The most frequent grade 3 or 4 adverse event was diarrhea. No treatment-related deaths were reported. Conclusion: The updated analysis demonstrated that pyrotinib could be a promising treatment option in HER2-positive MBC with acceptable toxicity in the real world. Survival is still under assessment with longer follow-up.

Background: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer associated with poor prognosis and limited treatment options. The androgen receptor (AR) has emerged as a potential therapeutic target for luminal androgen receptor (LAR) TNBC. However, multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits. This study aimed to investigate the role of AR in TNBC and its detailed mechanism. Methods: Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4 (NECTIN4) expression in TNBC tissues. Then, in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta (ERβ) in TNBC. Chromatin immunoprecipitation sequencing (ChIP-seq), co-immunoprecipitation (co-IP), molecular docking method, and luciferase reporter assay were performed to identify key molecules that affect the function of AR. Results: Based on the TNBC tissue array analysis, we revealed that ERβ and AR were positive in 21.92% (32/146) and 24.66% (36/146) of 146 TNBC samples, respectively, and about 13.70% (20/146) of TNBC patients were ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection in LAR TNBC cell lines but not in AR-negative TNBC. Mechanistically, we identified that NECTIN4 promoter –42 bp to –28 bp was an AR response element, and that ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression. Conclusions: This study suggests that ERβ functions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation. Therefore, our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

Aims: This study investigates the association between circulating tumor cells (CTCs) and breast cancer metastasis. Methods: A retrospective study was conducted using patients with histologically confirmed breast cancer recruited from the First Affiliated Hospital of Nanjing Medical University during the period of August 2017–October 2020. We used adjusted logistic regression, the random forest algorithm, and sensitivity analysis to study the association between CTC enumeration and tumor metastasis. Further, we performed next-generation sequencing (NGS) on the CTCs obtained from two patients with breast cancer brain metastasis. Results: A total of 41 out of 116 enrolled patients were identified with tumor metastasis. CTC enumeration was significantly higher in patients with liver metastasis than in those without liver metastasis. Patients with CTCs ≥ 5 exhibited a higher risk of tumor metastasis than those with CTCs < 5 in the adjusted model (odds ratios (OR) = 6.25, 95% confidence interval (CI) = 2.63–15.58). The random forest model identified CTC enumeration as a significant metastasis-related variable with the highest mean decrease accuracy and mean decrease Gini score. No significant association was found between CTCs and visceral metastasis with an OR of 1.29 (95% CI = 0.98–2.05, p = 0.232). Upon further investigating organ-specific metastasis, we found that patients with high CTC levels were more likely to develop liver metastasis (OR = 4.87, 95% CI = 1.34–20.17, p = 0.021). The NGS study of CTCs identified a total of 120 indel mutations (e.g., CNGB1, NTSR1, ZG16). The enriched biological processes were mechanoreceptor differentiation and macrophage activation involved in the immune response. The enriched KEGG pathways included focal adhesion, the PI3K-Akt signaling pathway, and microRNAs involved in cancer. Conclusions: Our study revealed that CTCs ≥ 5 are a risk factor for tumor metastasis in breast cancer patients. In addition, we reported that CTCs ≥ 5 might be associated with a higher risk of liver metastasis in patients with metastatic breast cancer. We have provided the mutational profiles of CTCs based on next-generation sequencing.

A 3D Electrical Impedance Tomography (EIT) method based on Dimensional Grey Wolf Optimization (DGWO) algorithm is proposed for reconstructing 3D images of breast tumors, overcomes the inherent defects of 3D EIT with high shape sensitivity and position sensitivity. In this study, a combination of multiple ellipsoids is used to mimic the shape of a breast tumor. The EIT problem is transformed into an optimization problem, which is solved by constructing an objective function and employing a sensitivity matrix approach. Finally, the optimization problem is solved using DGWO algorithm. In the simulation, a 16-electrode tapered sensor is used to randomly generate a tumor model and compared with the Tikhonov regularization algorithm and the combination of Tikhonov and NOSER regularization algorithm (TK-NOSER) to validate the performance of the proposed algorithm. Simulation results show that the DGWO algorithm differs little from the traditional regularization algorithm when the target is located in the center, while the advantage of the DGWO algorithm is more obvious when the target is located at the edge and non-spherical. DGWO algorithm improves the image correlation coefficient (IC) and image error (IE) by 12.20% and 24.00%, respectively, when the target is at the edge position. In the experiment, water and agar models of specific conductivity were used to simulate mammary glands and tumors. The experimental results show that the DGWO algorithm is superior to the TK-NOSER algorithm in terms of imaging accuracy and imaging artifacts, in which the average IC and average IE of the DGWO algorithm are improved by 19.14% and 15.12%, respectively. Therefore, the constructed experimental platform and the proposed algorithm achieve accurate imaging of target size and shape, which is expected to be applied to the clinical detection of breast cancer.