Background: It is estimated that breast cancer (BC) incidence, especially that of early-stage breast cancer cases continues to rise due to increased universal screening. Breast-conserving surgery (BCS) is the main intervention for early-stage BC. Lympho-vascular invasion (LVI) is reported to influence breast cancer prognosis but its prognostic value in breast-conserving treatment is controversial. Methods: A search was conducted on the Cochrane library, PubMed, Web of Science, and EMBASE from inception to December 1^st, 2021, without language restrictions, to identify studies that explored the prognosis of lympho-vascular invasion in breast-conserving surgery. Reviews of each study were conducted, and data extracted. The meta-analysis was performed with StataSE 16. Study quality assessment was evaluated using the Newcastle–Ottawa Scale. Results: Overall, 15 studies with 21,704 patients deemed eligible for this study. Event-free survival (EFS), disease-free survival (DFS), overall survival (OS), distant metastases (DM), loco-regional recurrence (LRR), local recurrence (LR), breast recurrence (BR), disease specific survival (DSS), and breast cancer specific survival (BCSS), were extracted from each study. We found that LVI leads to poor OS (HR = 1.46, 95% CI: 1.17–1.83), DM (HR = 2.08, 95% CI: 1.66–2.60) and LR (HR = 2.00, 95% CI: 1.54–2.61). Conclusions: We confirmed that early-stage BC patients with LVI-positive have poorer OS, DFS, LRR, BCSS, DM and LR following receiving BCS than those LVI-negative patients. Mastectomy, in combination with radical systemic therapies could be considered, especially in those requiring second surgery. How to change the impact of LVI on the local recurrence rate and long-term survival in patients who undergo BCS may be a valuable research direction in the future.

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent cancers, and PANoptosis is a distinct, inflammatory-programmed cell death regulated by the PANoptosome. The essential regulators of cancer occurrence and progression are microRNAs (miRNAs). However, the potential function of PANoptosis-related microRNAs (PRMs) in ccRCC remains obscure. This study retrieved ccRCC samples from The Cancer Genome Atlas database and three Gene Expression Omnibus datasets. PRMs were recognized based on previous reports in the scientific literature. Regression analyses were used to identify the prognosis PRMs and construct a PANoptosis-related miRNA prognostic signature based on the risk score. We discovered that high-risk patients had poorer survival prognoses and were significantly linked to high-grade and advanced-stage tumors, using a variety of R software packages and web analysis tools. Furthermore, we demonstrated that the low-risk group had significant changes in their metabolic pathways. In contrast, the high-risk group was characterized by high immune cell infiltration, immune checkpoint expression, and low half-maximum inhibition concentration (IC50) values of chemotherapeutic agents. This suggests that high-risk patients may benefit more from immunotherapy and chemotherapy. In conclusion, we constructed a PANoptosis-related microRNA signature and revealed its potential significance in clinicopathological features and tumor immunity, thereby providing new precise treatment strategies.

The aim of current study was to use competing risk model to assess whether medullary carcinoma of the breast (MCB) has a better prognosis than invasive ductal carcinomas of breast cancer (IDC), and to build a competing risk nomogram for predicting the risk of death of MCB. We involved 3,580 MCB patients and 319,566 IDC patients from Surveillance, Epidemiology, and End Results (SEER) database. IDC was found to have a worse BCSS than MCB (Hazard ratio (HR) > 1, p < 0.001). The 5-year cumulative incidences of death (CID) was higher in IDC than MCB (p < 0.001). Larger tumor size, increasing number of positive lymph nodes and unmarried status were found to worsen the BCSS of MCB (HR > 1, p < 0.001). We found no association between ER, PR, radiotherapy or chemotherapy and MCB prognosis (p > 0.05). After a penalized variable selection process, the SH model-based nomogram showed moderate accuracy of prediction by internal validation of discrimination and calibration with 1,000 bootstraps. In summary, MCB patients had a better prognosis than IDC patients. Interestingly, unmarried status in addition to expected risk factors such as larger tumor size and increasing number of positive lymph nodes were found to worsen the BCSS of MCB. We also established a competing risk nomogram as an easy-to-use tool for prognostic estimation of MCB patients.

As the first anti-HER2 targeted agent approved by FDA in 1998, Trastuzumab has significantly improved the outcome of patients with HER2 positive metastatic breast cancer. Unfortunately, resistance to trastuzumab is a severe obstacle to its therapeutic efficacy in clinical application, and its mechanism has not yet been fully elucidated. In our study, we found that stabilization of cyclin D3 could be one reason for trastuzumab resistance. Trastuzumab could induce G1/G0 phase arrest by downregulating cyclin D3 protein expression. However, the protein expression of cyclin D3 was not affected in trastuzumab-resistant cells, which might be related to aberrant activation of ERK signaling pathway. Furthermore, degradation of cyclin D3 protein by trastuzumab was mainly resulted from ubiquitin-dependent proteasome mechanism instead of transcriptional regulation. In trastuzumab-resistant breast cancer cells, trastuzumab-induced degradation of cyclin D3 protein was abrogated. When the ubiquitin pathway was inhibited, cells would show a predisposition to resistance to trastuzumab. Further, CDK4/6 inhibitor can inhibit the proliferation of trastuzumab-resistant HER-2 positive breast cancer cells. Therefore, combination of CDK4/6 inhibitors and anti-HER2 targeted therapy may be an alternative and promising strategy to overcome trastuzumab resistance in the future.