Abstract
Abstract Background: Increasing evidence suggests carotenoids, micronutrients in fruits and vegetables, reduce the risk of breast cancer. The importance of timing of carotenoids exposure prior to breast cancer diagnosis has not been thoroughly explored, and limited analyses have been conducted by breast tumor subtype. Methods: We conducted a nested case-control study of plasma carotenoids and risk of breast cancer in the Nurses' Health Study (NHS). In 1989-90, 32,826 women donated blood samples; in 2000-02, 18,473 of these women contributed a second blood sample. Between the first blood collection in 1989-90 and June 2010, 2,148 cases of breast cancer were diagnosed (579 after the second collection). One control was matched to each case. Carotenoids were measured in archived plasma samples by reverse-phase high-performance liquid chromatography. Using unconditional logistic regression, adjusting for matching factors and several breast cancer risk factors, we calculated relative risks (RRs) and 95% confidence intervals (CIs). Results: Carotenoid levels measured 10 years apart were modestly correlated, with intraclass correlation coefficients (ICCs) ranging from 0.30 (β-carotene) to 0.54 (lutein/zeaxanthin). Higher levels of α-carotene, β-carotene, lycopene, and total carotenoids were associated with 18-28% statistically significant lower risks of breast cancer (e.g., β-carotene top vs. bottom quintile RR=0.72, 95% CI (0.59-0.88), p-trend<0.001). The associations between plasma carotenoid levels and breast cancer risk were suggestively stronger for carotenoids measured 10 or more years prior to diagnosis (e.g., total carotenoids top vs. bottom quintile RR=0.69, 95% CI (0.50-0.95), p-trend=0.01) than for measures <10 years before diagnosis (RR=0.79, 95% CI (0.64-0.98), p-trend=0.05), though the difference was not statistically significant (p-interaction=0.08). No statistically significant differences in associations were observed between estrogen receptor (ER)-positive and ER-negative tumors. Associations were suggestively stronger for luminal B, compared with luminal A, tumors (e.g., β-carotene top vs. bottom quintile RR (95% CI): luminal B=0.52 (0.32-0.85), p-trend=0.01; luminal A=0.82 (0.61-1.11), p-trend=0.10). Carotenoid levels were strongly inversely associated with breast cancer recurrence and death (e.g., β-carotene top vs. bottom quintile RR=0.31, 95% CI (0.20-0.49), p-trend<0.0001). Conclusions: This large prospective analysis with 20 years of follow-up suggests women with higher circulating levels of α-carotene, β-carotene, lycopene, and total carotenoids may be at reduced breast cancer risk, particularly more aggressive and ultimately fatal disease. In addition, although associations with distant measures were slightly stronger, carotenoid measures both within 10 years and 10-20 years prior to diagnosis appear to be associated with lower risk. Citation Format: A. Heather Eliassen, Xiaomei Liao, Shelley S. Tworoger, Susan E. Hankinson. Plasma carotenoids and risk of breast cancer over 20 years of follow-up in the Nurses' Health Study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2919. doi:10.1158/1538-7445.AM2014-2919
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