Multiomics and single‐cell sequencings reveal the specific biological characteristics of low Ki‐67 triple‐negative breast cancer

Abstract Background Triple‐negative breast cancer (TNBC) displays high heterogeneity. The majority of TNBC cases are characterized by high Ki‐67 expression. TNBC with low Ki‐67 expression accounts for only a small fraction of cases and has been relatively less studied. Methods This study analyzed a large single‐center multiomics TNBC data set, combined with a single‐cell data set. The clinical, genomic, and metabolic characteristics of patients with low Ki‐67 TNBC were analyzed. Results The clinical and pathological characteristics were analyzed in 2217 TNBC patients. Low Ki‐67 TNBC was associated with a higher patient age at diagnosis, a lower proportion of invasive ductal carcinoma, increased alterations in the PI3K‐AKT‐mTOR pathway, upregulated lipid metabolism pathways, and enhanced infiltration of M2 macrophages. High Ki‐67 TNBC exhibited a higher prevalence of TP53 gene mutations, elevated nucleotide metabolism, and increased infiltration of M1 macrophages. Conclusions We identified specific genomic and metabolic characteristics unique to low Ki‐67 TNBC, which have implications for the development of precision therapies and patient stratification strategies.