Premenopausal plasma carotenoids, fluorescent oxidation products, and subsequent breast cancer risk in the nurses’ health studies

Two prospective cohorts (Nurses' Health Study and Nurses' Health Study II) with a nested case-control design; female nurses; premenopausal at blood collection for carotenoid analyses; 1,179 case-control pairs; cases diagnosed with breast cancer; controls matched on age, time of blood draw, fasting status, and menopausal status; plasma carotenoids measured by HPLC; fluorescent oxidation products (FlOPs) measured in a subset; 45 SNPs genotyped; analysis used conditional logistic regression.

Carotenoids measured in premenopausal plasma were not inversely associated with overall breast cancer risk (total carotenoids top vs bottom quartile RR 0.99, 95% CI 0.77–1.28; p-trend = 0.67). No differences by estrogen receptor status. Lycopene showed a potential inverse association with postmenopausal breast cancer (top vs bottom quartile RR 0.66, 95% CI 0.45–0.96; p-trend = 0.02). FlOP biomarkers were not positively associated with risk; FlOP_360 top vs bottom RR 0.68 (95% CI 0.50–0.95; p-trend = 0.07); FlOP_320 RR 0.76 (95% CI 0.55–1.06; p-trend = 0.08). Significant interactions by menopausal status at diagnosis for α-carotene, β-carotene, and total carotenoids, with inverse associations largely among postmenopausal at diagnosis. Some SNP interactions with carotenoids on risk observed (e.g., CAT rs11032686 per-allele OR 1.31; 95% CI 1.02–1.67; rs7947841 per-allele OR 1.36; 95% CI 1.07–1.74). Overall interpretation: no strong evidence that premenopausal carotenoids reduce breast cancer risk; protective signals may be limited to postmenopausal cancers and depend on hormonal context and exposure timing. Results are exploratory and require replication; do not yet justify carotenoid supplementation for breast cancer prevention.

Biomarkers measured at a single time point; potential measurement error and batch variability (recalibrated)); multiple statistical tests without formal adjustment; residual confounding possible due to observational design; limited generalizability beyond premenopausal, female nurses and specific exposure window.