Abstract
BACKGROUND: Healthy lifestyles and screening are the two major interventions to prevent breast cancer mortality. However, their effects have not been compared simultaneously, and it remains unclear whether their benefits differ by women' baseline breast cancer risk.</p>
METHODS: A prospective cohort study was conducted using the UK biobank linked to national cancer registries, including 261 398 women aged 40-70. Hazard ratios (HRs) and population attributable fractions (PAF) for breast cancer mortality were estimated in relation to healthy lifestyle index (HLI) and screening status, using a Cox regression model. We further examined the interaction between HLI, screening and breast cancer risk predictors (Tyrer-Cuzick score and polygenic risk score [PRS], using highest and lowest 20% as high- and low-risk groups) for breast cancer mortality by likelihood ratio (LR) test.</p>
RESULTS: Women with a high Tyrer-Cuzick score and PRS were associated with increased breast cancer mortality. HLI was inversely associated with breast cancer mortality (HR = 0.55, 95%CI = 0.42-0.72), and the effect did not differ statistically according to the risk scores. Women who participated in screening programs were at reduced risk of breast cancer mortality (HR = 0.70, 95% CI = 0.52-0.95), particularly among those women with high Tyrer-Cuzick score (P for interaction = .048). The fraction of breast cancer mortality cases that might be prevented (PAF) by screening was 14.27% (95%CI = 4.44-24.09) and by healthy lifestyle was 9.63% (95%CI = 3.10-16.16).</p>
CONCLUSIONS: Although women with a high PRS or Tyrer-Cuzick score is associated with increased breast cancer mortality, deaths are preventable through changing lifestyles and screening. These findings support personalized, risk-based strategies.</p>