Background: Whether health inequalities of disease burden and medical utilization exist by ethnicity in Asian breast cancer (BC) patients remains unclear. The authors aim to measure ethnic disparities in disease burden and utilization among Mongolian and Han female BC patients in China. Materials and methods: Based on data extracted from Inner Mongolia Regional Health Information Platform, a retrospective cohort study was established during 2012–2021. Disease burden including incidence, 5-year prevalence, mortality, survival rate, and medical cost were analyzed and compared between Han and Mongolian patients. Results: A total of 34 878 female patients [mean (SD) age, 52.34 (10.93) years] were included among 18.19 million Chinese, and 4315 (12.03%) participants were Mongolian. Age-standardized rates of incidence are 32.68 (95% CI: 20.39–44.98) per 100 000. Higher age-specific incidence and 5-year prevalence were observed in Mongolian than in Han. The cost of BC annually per capita was significantly lower for Mongolian than Han [$1948.43 (590.11–4 776.42) vs. $2227.35 (686.65–5929.59), P<0.001]. Mongolian females showed higher all-cause mortality [30.92 (95% CI: 28.15–33.89) vs. 27.78 (95% CI: 26.77–28.83) per 1000, P=0.036] and BC-specific mortality [18.78 (95% CI: 16.64–21.13) vs. 15.22 (95% CI: 14.47–16.00) per 1000, P=0.002] than Han females. After adjusting covariates, Mongolian were associated with increased all-cause mortality [HR, 1.21, (95% CI: 1.09–1.34); P<0.001] and BC-specific mortality [HR, 1.31, (95% CI: 1.14–1.49); P<0.001]. Conclusion: The findings of this cohort study highlight a higher level of disease burden with unmet medical demand in Mongolian patients, suggesting that more practical efforts should be made for the minority. Further research is needed to explore the concrete mechanisms of the disparities as well as eliminate health disproportion.

Recent clinical trials have suggested that solid cancers with mismatch repair (MMR) deficiency are highly responsive to immunotherapy, regardless of cancer types. Previous MMR-related studies on breast cancer have predominantly focused on germline variants. However, the somatic MMR alterations have not been comprehensively characterized in breast cancer. In this study, we integrated genomic, transcriptomic, and clinical data from over 3000 breast cancer cases across six public cohorts. Our findings revealed that 1.2% of breast cancers harbored oncogenic somatic MMR alterations, with triple-negative breast cancer (TNBC) demonstrating the highest mutation rate at 3.1%. Additionally, somatic MMR alterations were significantly associated with microsatellite instability-high (MSI-H) and MMR-related mutational signatures, indicating that somatic MMR alterations led to impaired function of the MMR system. Biallelic inactivation of MMR genes resulted in a more pronounced loss of MMR function compared to monoallelic inactivation. Importantly, these MMR alterations significantly increased the tumor mutational burden (TMB) and neoantigen load in breast cancer, regardless of MSI-H status. These findings indicate that the frequency of MMR alterations is highest in TNBC and that MMR alterations in breast cancer can lead to MMR functional deficiencies, suggesting that some patients harboring such alterations may benefit from immunotherapy.

Review Article Round table discussion: strategies for the treatment of HER2-positive advanced breast cancer in the rising age of antibody-drug conjugates Ying Yan, Qiao Li, Jianbin Li

The JAK-STAT signaling pathway serves as a critical hub for cytokine signal transduction, and its aberrant activation plays a decisive role in shaping the immune microenvironment of breast cancer. This review systematically elucidates how this pathway contributes to the construction of an immunosuppressive microenvironment through upregulating PD-L1 expression, recruiting and activating myeloid-derived suppressor cells (MDSCs), promoting regulatory T cell (Treg) generation, while concomitantly suppressing the functions of CD8+ T cells and natural killer (NK) cells. Although targeted therapy against this pathway, particularly in combination with immune checkpoint inhibitors, has demonstrated promising potential, several challenges remain, including pathway compensation, low inhibitor selectivity, associated toxicities, and the lack of predictive biomarkers. Future directions should focus on the development of highly selective STAT inhibitors, exploration of immunophenotype-guided combination strategies, establishment of robust biomarker systems, and in-depth investigation of the dynamic interplay between this pathway and the immune microenvironment, thereby providing a theoretical foundation for combined immunotherapy in breast cancer.