Prediagnostic circulating carotenoids and lethal breast cancer risk: a novel analytic approach applied to a nested...

Identifying prediagnostic modifiable factors that are associated with lethal breast cancer risk may provide prevention strategies for fatal disease.

We sought to examine whether prediagnostic circulating carotenoids and retinol concentrations are associated with a lower risk of lethal breast cancer using multistate modeling.

This is a nested case-control study including 3516 controls and 2583 incident invasive breast cancer cases, among whom 190 developed lethal breast cancer (experienced recurrence or died due to breast cancer) over three 10-y intervals. Prediagnostic plasma carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein/zeaxanthin) and retinol were assayed using high-performance liquid chromatography; total carotenoids were calculated as the sum of individual carotenoids. On the basis of a multistate model that combined separate estimates for breast cancer incidence and recurrence/mortality due to breast cancer among invasive cases, we examined the association between prediagnostic circulating carotenoids and retinol and the probability of transitioning from disease-free to invasive breast cancer to breast cancer recurrence/death >30 y.

Compared with the lowest quintile, females in the highest quintile of β-carotene had a 41% lower risk of lethal breast cancer {β-carotene hazard ratio (HR) = 0.59 [95% confidence interval (CI): 0.41, 0.83], P_trend < 0.01}; for β-cryptoxanthin, HR was 0.68 (95% CI: 0.47, 0.97); for total carotenoids, risk of lethal breast cancer was 48% lower [HR = 0.52 (95% CI: 0.36, 0.74), P_trend < 0.01], which for β-carotene and total carotenoids captured the combined protective effects of incidence and recurrence/mortality, while for β-cryptoxanthin, reflected protective effects of recurrence/mortality but not for incidence. For β-carotene, stronger inverse associations were observed for postmenopausal females (P_{heterogeneity} < 0.01), and marginally stronger for ever smokers (P_{heterogeneity} = 0.11), and for females with BMI < 25 kg/m² (P_{heterogeneity} = 0.10). Other plasma carotenoids or retinol were not associated with reduced lethal breast cancer risk.

Higher prediagnostic β-carotene, β-cryptoxanthin, and total carotenoid concentrations may be associated with a lower likelihood of progression from a cancer-free state to fatal breast cancer.