Epigenetic age acceleration measures and chemotoxicity in older adults with early breast cancer

Among older adults with early breast cancer, the risk of chemotoxicity can vary widely despite similar chronological age. Here, we evaluated whether epigenetic indicators of biological age can stratify the risk of chemotoxicity in this population. In a prospective study of 394 women age > 65 with stage I-III breast cancer treated with neo/adjuvant chemotherapy, we analyzed peripheral blood DNA methylation patterns to estimate epigenetic age acceleration (EAA) before chemotherapy. We tested five epigenetic clocks. The primary endpoint was grade 2+ chemotoxicity (yes/no, yes defined as any grade 2+ toxicity attributed to chemotherapy). Using multivariable logistic regression, we examined the association between EAA and grade 2+ chemotoxicity, adjusting for demographic, clinical, and geriatric covariates. We also evaluated the relationship between EAA and individual grade 2+ toxicities. The median (range) pre-treatment chronological age was 70 years (65-85); 65% had stage II/III disease; 38% received anthracycline; and 75% received G-CSF prophylaxis. A total of 334 (84.8%) participants experienced a grade 2+ toxicity. After multivariable adjustment, there was no significant association between measures of EAA and grade 2+ chemotoxicity. For individual toxicities, EAA by GrimAge was associated with increased risk for infection without neutropenia, and EAA by DunedinPACE was associated with increased risk for diarrhea. In this cohort of older adults with early breast cancer, there was no significant association between pre-treatment EAA and overall grade 2+ chemotoxicity. Further research is needed to examine whether blood-based biomarkers of aging may identify older adults at high risk of chemotoxicity. NCT01472094, Hurria Older PatiEnts (HOPE) with Breast Cancer Study.