Abstract
BACKGROUND: Metabolism-related metrics have been widely investigated for their relationship with breast cancer risk but are mostly based on single values. Weight gain during adulthood has been related to an increased risk of breast cancer, while the relationship with changes in glucose and lipids remain largely unknown. METHODS: Women aged 20-80 were included from the general population-based Lifelines cohort when they had two assessments: 2007-2013 and 2014-2017. The following metrics were measured once at each of the two periods: body mass index (BMI), waist to height ratio (WHtR), hemoglobin A1c (HbA1c), HDL cholesterol (HDL-C), total cholesterol (TC), and triglyceride (TG). Women with a history of cancer, follow up less than 12 months, or who were pregnant during assessments were excluded. Mean annual changes (mean ACs) were calculated for each metric between the two periods, and further categorized into three groups - decrease, no change, and increase. Cox proportional hazards models were conducted to estimate their associations with breast cancer occurrence, reporting adjusted hazard ratios (aHR) with 95% confidence intervals (CI). RESULTS: During a median of 92.3 months follow-up, 1,202 of 58,785 women were diagnosed with breast cancer. Among women with a baseline BMI < 25 kg/m(2), a negative association between BMI decrease and breast cancer risk was observed in contrast to their counterparts with no change (aHR: 0.75, 95% CI: 0.56-0.99). In addition, relative to the no change group, breast cancer risk was positively associated with reductions in HbA1c (aHR: 1.23, 95% CI: 1.07-1.40) and TG (aHR: 1.26, 95% CI: 1.06-1.49). CONCLUSIONS: Changes over time in this real-world dataset from the general population highlight the benefits of weight loss and the harms of decreased glucose and TG in relation to breast cancer risk. These longitudinal patterns are affected by age, BMI, and initial values, emphasizing the importance of personalized metabolic health management.