Search

Background: Breast cancer is a common cancer type that leads to cancer-related deaths among women. HER2-positive breast cancer, in particular, is associated with poor prognosis due to its high aggressiveness, increased risk of recurrence, and metastasis potential. Previous observational studies have explored potential associations between inflammatory cytokines and the risk of two breast cancer subtypes (HER2-positive and HER2-negative), but the results have been inconsistent. To further elucidate the causal relationship between inflammatory cytokines and the two breast cancer subtypes, we conducted a two-sample Mendelian randomization (MR) study. Methods: We employed a two-sample bidirectional MR analysis using publicly available genome-wide association study (GWAS) statistics. After obtaining instrumental variables, we conducted MR analyses using five different methods to ensure the reliability of our results. Additionally, we performed tests for heterogeneity and horizontal pleiotropy. Subsequently, we conducted a reverse MR study by reversing exposure and outcome variables. Results: Evidence from our IVW analysis revealed that genetically predicted levels of IL-5 [odds ratio (OR): 1.18, 95% confidence interval (CI): 1.04–1.35, P = 0.012], IL-7 (OR: 1.11, 95% CI: 1.01–1.22, P = 0.037), and IL-16 (OR: 1.13, 95% CI: 1.02–1.25, P = 0.025) were associated with an increased risk of HER2-positive breast cancer. Conversely, IL-10 (OR: 1.14, 95% CI: 1.03–1.26, P = 0.012) was associated with an increased risk of HER2-negative breast cancer. These results showed no evidence of heterogeneity or horizontal pleiotropy (P > 0.05). Results from the reverse MR analysis indicated no potential causal association between breast cancer and inflammatory cytokines (P > 0.05). Conclusion: Our findings demonstrate that IL-5, IL-7, and IL-16 are risk factors for HER2-positive breast cancer, with varying degrees of increased probability of HER2-positive breast cancer associated with elevated levels of these inflammatory cytokines. Conversely, IL-10 is a risk factor for HER2-negative breast cancer. Reverse studies have confirmed that breast cancer is not a risk factor for elevated levels of inflammatory cytokines. This series of results clarifies the causal relationship between different types of inflammatory cytokines and different subtypes of breast cancer. Based on this research, potential directions for the mechanism research of different inflammatory cytokines and different subtypes of breast cancer have been provided, and potential genetic basis for identifying and treating different subtypes of breast cancer have been suggested. [ABSTRACT FROM AUTHOR]

On the basis of the expression of specific genes, breast cancer is classified into four molecular types: Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER-2)-positive, and triple negative. By summarizing and analyzing the studies published in the past decade, including the correlation between molecular types of breast cancer and traditional Chinese medicine(TCM) patterns, as well as the connection between the TCM constitution and clinical characteristics of different molecular types of breast cancer, this study reveals that there are differences in TCM patterns between different types of breast cancer. Notably, the pattern of liver depression and qi stagnation and the pattern of thoroughfare-controlling vessel disharmony are common contributors to the development of Luminal A and B breast cancer. In patients with HER-2-positive breast cancer, the main pathogenic mechanism is that wind, an exterior pathogen in Chinese medicine, complicated with phlegm and static blood, flows through the channels. In patients with triple-negative breast cancer, toxin, phlegm, and static blood are cemented in the channels. Therefore, in TCM-based diagnosis and treatment of breast cancer, it is necessary to make targeted changes according to the pathogenesis characteristics of different molecular types based on the core treatment principle of soothing the liver and invigorating the spleen, paying attention to the balance of qi, blood, and yin and yang and achieving accurate TCM differentiation and treatment with the integration of disease differentiation, molecular typing, and pattern differentiation. [ABSTRACT FROM AUTHOR]