Abstract
Breast cancer is one of the most common malignancies in women. This study aimed to explore the association between healthy lifestyle, biological aging and breast cancer risk in pre- and postmenopausal women. This study included 125,579 participants. Biological aging was calculated using the PhenoAge algorithm. Cox regression models and counterfactual mediation analysis was utilized. During an average follow-up of 13.65 years, 5418 breast cancers occurred. In the overall women participants, compared to the healthy lifestyle group, the HR (95% CI) for unhealthy lifestyle regarding incident breast cancer was 1.28 (1.13, 1.33). Compared to the lowest tertile of accelerated aging (AA), the HR (95% CI) for the highest tertile regarding breast cancer risk was 1.22 (1.14, 1.30). Consistent results observed only in postmenopausal participants. The joint effect of a healthy lifestyle and AA on breast cancer risk was statistically significant (P < 0.001). The AA-mediated breast cancer risk ratio was 17.69 (95% CI 8.19, 27.19) when comparing healthy to unhealthy lifestyles. In the study, healthy lifestyle and lower levels of AA were significantly associated with a reduced risk of breast cancer, particularly among postmenopausal women. In addition, AA mediated 17.02-17.69% of the link between lifestyle and breast cancer risk.