The American journal of clinical nutrition · 2026
Prediagnostic circulating carotenoids and lethal breast cancer risk: a novel analytic approach applied to a nested case-control study.
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Peng Cheng, Chai Boyang, Tamimi Rulla M, Chen Wendy Y, Holmes Michelle D, Willett Walter C, Eliassen A Heather, Rosner Bernard A
Аннотация
BACKGROUND: Identifying prediagnostic modifiable factors that are associated with lethal breast cancer risk may provide prevention strategies for fatal disease.
OBJECTIVES: We sought to examine whether prediagnostic circulating carotenoids and retinol concentrations are associated with a lower risk of lethal breast cancer using multistate modeling.
METHODS: 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.
RESULTS: 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], Ptrend < 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), Ptrend < 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 (Pheterogeneity < 0.01), and marginally stronger for ever smokers (Pheterogeneity = 0.11), and for females with BMI < 25 kg/m2 (Pheterogeneity = 0.10). Other plasma carotenoids or retinol were not associated with reduced lethal breast cancer risk.
CONCLUSIONS: 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.
OBJECTIVES: We sought to examine whether prediagnostic circulating carotenoids and retinol concentrations are associated with a lower risk of lethal breast cancer using multistate modeling.
METHODS: 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.
RESULTS: 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], Ptrend < 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), Ptrend < 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 (Pheterogeneity < 0.01), and marginally stronger for ever smokers (Pheterogeneity = 0.11), and for females with BMI < 25 kg/m2 (Pheterogeneity = 0.10). Other plasma carotenoids or retinol were not associated with reduced lethal breast cancer risk.
CONCLUSIONS: 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.