Abstract 4109: Accelerated aging in breast cancer survivors: the role of therapy-induced epigenetic modifications

Abstract Breast cancer affects over 300, 000 individuals annually in the United States, with survival rates improving due to advances in chemotherapy, radiation, hormonal, and targeted therapies. However, these treatments may inadvertently accelerate biological aging through epigenetic modifications, including DNA methylation, histone alterations, and changes in non-coding RNAs. This review explores how breast cancer therapies impact aging-related epigenetic pathways. Chemotherapy induces cellular senescence by altering DNA methylation patterns and histone modifications, potentially leading to the early onset of age-related diseases. Targeted therapies also affect epigenetic regulation, influencing gene expression related to cell cycle control, apoptosis, and DNA repair. Non-coding RNAs, such as microRNAs and long non-coding RNAs, are essential gene expression regulators affected by cancer treatments. They play significant roles in cellular senescence and therapeutic resistance, adding complexity to the aging phenotype observed in survivors. Clinical manifestations like cardiovascular dysfunction, endocrine disorders, and systemic inflammation are linked to therapy-induced epigenetic changes and in turn accelerated aging. Emerging epigenetic therapies targeting DNA methylation and histone modifications offer potential strategies to mitigate treatment-induced aging effects. DNA methyltransferase inhibitors and histone deacetylase inhibitors show promise in reactivating silenced genes and enhancing therapy sensitivity. Non-pharmacological approaches, including exercise, dietary modifications rich in bioactive compounds, and gut microbiota modulation, may also counteract therapy-exacerbated aging processes. In conclusion, existing evidence shows that cancer therapies are associated with decreased cardiorespiratory fitness, increased risk of cardiomyopathy, osteoporosis, and metabolic dysregulation, contributing to accelerated biological aging via diverse epigenetic mechanisms. Recognizing these changes is crucial for developing interventions that survivor’s health and quality of life. Further research is needed to fully understand therapy-induced epigenetic alterations and their long-term impacts, facilitating personalized survivorship care that addresses this population’s aging complexities. Citation Format: Nikita Nikita, Zhengyang Sun, Swapnil Sharma, Amy Shaver, Victoria Seewaldt, Ana Maria Lopez, Grace Lu Yao. Accelerated aging in breast cancer survivors: the role of therapy-induced epigenetic modifications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4109.