Purpose: Several circulating carotenoids have been inversely associated with postmenopausal breast cancer risk in large cohort studies and a pooled analysis. Whether associations differ by tumor or participant characteristics remains unclear. We investigated the associations of plasma carotenoids with postmenopausal breast cancer risk overall and by estrogen receptor (ER) status, tumor stage, smoking status, and body mass index, in a case–control study nested in the Cancer Prevention Study II Nutrition Cohort.

Methods: A total of 496 invasive breast cancer cases diagnosed between blood draw in 1998–2001 and June 30, 2007 and matched 1:1 with controls on race, birth date, and blood draw date were included. Multivariable-adjusted conditional and unconditional logistic regression models were used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs).

Results: Plasma α-carotene above the lowest quartile was associated with significant 40–43 % lower risk of invasive breast cancer risk (fourth vs. first quartile OR 0.60, 95 % CI 0.41–0.87, P-trend = 0.037) after adjustment for multiple covariates. This inverse association was strengthened after further adjustment for other plasma carotenoids and total fruit and vegetable intake (fourth vs. first quartile OR 0.50, 95 % CI 0.29–0.85, P-trend = 0.041). Other plasma carotenoids or total carotenoids were not associated with breast cancer risk. The inverse association of α-carotene with breast cancer remained for ER+, but not for ER− tumors, although test for heterogeneity was not statistically significant (P-heterogeneity = 0.49).

Conclusions: These results suggest that higher plasma α-carotene is associated with lower risk of invasive breast cancer.