Molecular classification of geriatric breast cancer displays distinct senescent subgroups of prognostic significance.

Breast cancer in the elderly presents distinct biological characteristics and clinical treatment responses compared with cancer in younger patients. Comprehensive Geriatric Assessment is recommended for evaluating treatment efficacy in elderly cancer patients based on physiological classification. However, research on molecular classification in older cancer patients remains insufficient. In this study, we identified two subgroups with distinct senescent clusters among geriatric breast cancer patients through multi-omics analysis. Using various machine learning algorithms, we developed a comprehensive scoring model called "Sene_Signature," which more accurately distinguished elderly breast cancer patients compared with existing methods and better predicted their prognosis. The Sene_Signature was correlated with tumor immune cell infiltration, as supported by single-cell transcriptomics, RNA sequencing, and pathological data. Furthermore, we observed increased drug responsiveness in patients with a high Sene_Signature to treatments targeting the epidermal growth factor receptor and cell-cycle pathways. We also established a user-friendly web platform to assist investigators in assessing Sene_Signature scores and predicting treatment responses for elderly breast cancer patients. In conclusion, we developed a novel model for evaluating prognosis and therapeutic responses, providing a potential molecular classification that assists in the pre-treatment assessment of geriatric breast cancer.