Triple negative breast cancer (TNBC) is a heterogeneous disease and is highly related to immunomodulation. As we know, the most effective approach to treat TNBC so far is still chemotherapy. Chemotherapy can induce immunogenic cell death, release of damage-associated molecular patterns (DAMPs), and tumor microenvironment (TME) remodeling; therefore, it will be interesting to investigate the relationship between chemotherapy-induced TME changes and TNBC immunomodulation. In this review, we focus on the immunosuppressive and immunoreactive role of TME in TNBC immunomodulation and the contribution of TME constituents to TNBC subtype classification. Further, we also discuss the role of chemotherapy-induced TME remodeling in modulating TNBC immune response and tumor progression with emphasis on DAMPs-associated molecules including high mobility group box1 (HMGB1), exosomes, and sphingosine-1-phosphate receptor 1 (S1PR1), which may provide us with new clues to explore effective combined treatment options for TNBC.

The advent of molecular classification has ushered breast cancer treatment into the era of precision medicine. Nevertheless, clinical management continues to face significant challenges posed by drug resistance and tumor heterogeneity. Recent advances have identified novel programmed cell death (PCD) mechanisms-including ferroptosis, cuproptosis, disulfidptosis, and pyroptosis-as critical regulators of breast cancer progression, therapeutic responsiveness, and immune microenvironment remodeling. This review systematically elucidates the mechanistic foundations of these PCD pathways and investigates their molecular regulatory networks within breast cancer pathogenesis. Furthermore, we evaluate current targeted intervention strategies and assess their clinical translation potential, ultimately providing a theoretical framework for pioneering therapeutic approaches.

Purpose: PD-L1 is highly expressed in multiple cancers and suppresses anticancer immunity. HIF-1α, as a vital transcription factor, could regulate the proliferation, metastasis, and apoptosis of cancer cells. The aim of this study was to explore the correlation between PD-L1 and HIF-1α protein and further estimate its clinicopathological/prognostic impact on NSCLC patients. Methods: In this study, expression of PD-L1 and HIF-1α protein was detected by immunohistochemistry in tissue microarrays of NSCLC and non-cancerous tissues. Results: Expression of PD-L1 and HIF-1α protein was evidently elevated in NSCLC tissues compared with non-cancerous control lung tissues (both P<0.05). Also, PD-L1 was higher in male, lung SCC patients with lymph node metastasis (all P<0.05). There was a positive link between PD-L1 and HIF-1α in NSCLC (r=0.177, P=0.005). What's more, overall survival of lung ADC patients had to do with PD-L1 and clinical stage, while that of SCC patients was related to HIF-1α, pathological grade and LNM status (all P<0.05). Furthermore, multivariate analysis confirmed that PD-L1 and HIF-1α were considered to be independent prognostic factors for NSCLC patients (both P<0.05). Conclusion: PD-L1 and HIF-1α may serve as attractive independent worse prognostic biomarkers for NSCLC patients and the combined evaluation of PD-L1 and HIF-1α may also be valuable for prognosis judgment. Additionally, expression of PD-L1 was positively correlated with HIF-1α, which may provide evidences for a novel combinational therapy targeting PD-L1 and HIF-1α in NSCLC patients.

Bispecific antibody-drug conjugates (BsADCs) represent a promising strategy to overcome limitations of conventional ADCs in breast cancer, such as tumor heterogeneity and inefficient internalization. This review summarizes recent advances and the therapeutic potential of BsADCs. We conducted a literature review, focusing on BsADC candidates selected for clinical relevance (e.g., ZW49, BL-B01D1), mechanistic innovation (e.g., biparatopic targeting, engaging fast-internalizing receptors), and potential in challenging subtypes like triple-negative breast cancer (TNBC). BsADCs enhance drug delivery through dual targeting. Biparatopic HER2-targeting agents (e.g., ZW49, JSKN003) induce receptor clustering and robust internalization. BsADCs co-engaging rapidly internalizing receptors (e.g., HER2×CD63) hijack efficient endocytic pathways, showing activity even in low HER2-expression models. Furthermore, BsADCs targeting compensatory pathways, such as EGFR×HER3 (BL-B01D1) and TROP2×HER3 (JSKN016), have demonstrated breakthrough efficacy in TNBC. Optimization of linker technology and drug-to-antibody ratio (DAR) has improved stability and the therapeutic window, enabling the progression of several BsADCs into Phase III trials. BsADCs are a transformative therapeutic modality for breast cancer. Their ability to enhance tumor selectivity, overcome heterogeneity, and target resistant pathways positions them as key players in the future oncology landscape, with ongoing trials poised to define their clinical role.

Nipple-sparing mastectomy (NSM) and skin-sparing mastectomy (SSM) are widely accepted surgical options for breast cancer patients undergoing immediate reconstruction. However, the impact of preserving the nipple–areolar complex on patient-reported outcomes (PROs) remains uncertain, particularly in clinically matched settings. This retrospective study included patients who underwent unilateral NSM or SSM followed by immediate implant-based breast reconstruction at Hubei Cancer Hospital between January 2022 and January 2024. Patients were propensity score matched (2:1) based on age, body mass index, preoperative breast size, neoadjuvant chemotherapy, implant plane, and postmastectomy radiation therapy. PROs were assessed using the BREAST-Q (version 2.0) and the decision regret scale. Univariate and multivariate linear regression analyses were conducted to identify predictors of satisfaction and regret. A total of 87 patients were included after matching (NSM: n = 58; SSM: n = 29). NSM patients reported significantly higher satisfaction with breasts (mean 58.1 vs. 52.9, P = 0.038) and sexual well-being (mean 52.4 vs. 38.9, P = 0.035). Although psychosocial well-being and decision regret showed favorable trends in the NSM group, differences were not statistically significant. Multivariate analysis revealed that reduction in breast size was significantly associated with decreased satisfaction and psychosocial well-being, while increased breast size was linked to greater decision regret. No significant differences were observed in complication rates between groups. Notably, none of the SSM patients received nipple reconstruction during follow-up. NSM was associated with greater satisfaction in breast and sexual well-being compared to SSM in matched breast cancer patients undergoing implant-based reconstruction. These findings support prioritizing NSM when oncologically feasible and highlight the potential role of delayed nipple reconstruction and expectation management in improving postoperative satisfaction for SSM patients.

FAT4 is an extremely large atypical cadherin with crucial roles in the control of planar cell polarity (PCP) and regulation of the Hippo signaling pathway. Our study aims to clarify the FAT4 expression patterns, as well as the significance of FAT4 in predicting the prognosis and cancer immunity to non‐small cell lung cancer (NSCLC). FAT4 mRNA and protein expressions were both underregulated in NSCLC and associated with poor prognosis in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In addition, overexpress FAT4 with jujuboside A (JUA) or knockdown FAT4 with siRNA regulated the metastasis of LUAD through MAPK pathways. Moreover, the FAT4 expression included multiple immunological components to promote an immunosuppressive tumor microenvironment (TME). Furthermore, a study of the TCGA‐LUAD cohort's DNA methylation results showed that most FAT4 DNA CpG sites were typically hypermethylated in NSCLC relative to the normal lung tissue. The DNA CpG sites cg25879360 and cg26389756 of FAT4 were found to be strongly associated with FAT4 expression in LUAD through the correlation study. In conclusion, this is the first to report the potential function of FAT4 in NSCLC. Hence, FAT4 could be used as a promising prognostic and immunological biomarker for NSCLC.