title: Plasma carotenoids and risk of breast cancer over 20 y of follow-up.
abstract: BACKGROUND
  Increasing evidence suggests that carotenoids, which are micronutrients in fruit and vegetables, reduce breast cancer risk. Whether carotenoids are important early or late in carcinogenesis is unclear, and limited analyses have been conducted by breast tumor subtypes.
  
  
  OBJECTIVE
  We sought to examine issues of the timing of carotenoid exposure as well as associations by breast tumor subtypes.
  
  
  METHODS
  We conducted a nested case-control study of plasma carotenoids measured by using reverse-phase high-performance liquid chromatography and breast cancer risk in the Nurses' Health Study. In 1989-1990, 32,826 women donated blood samples; in 2000-2002, 18,743 of these women contributed a second blood sample. Between the first blood collection and June 2010, 2188 breast cancer cases were diagnosed (579 cases were diagnosed after the second collection) and matched with control subjects. RRs and 95% CIs were calculated by using conditional logistic regression adjusted for several breast cancer risk factors.
  
  
  RESULTS
  Higher concentrations of α-carotene, β-carotene, lycopene, and total carotenoids were associated with 18-28% statistically significantly lower risks of breast cancer (e.g., β-carotene top compared with bottom quintile RR: 0.72; 95% CI: 0.59, 0.88; P-trend < 0.001). Associations were apparent for total carotenoids measured ≥10 y before diagnosis (top compared with bottom quintile RR: 0.69; 95% CI: 0.50, 0.95; P-trend = 0.01) as well as those <10 y before diagnosis (RR: 0.79; 95% CI: 0.64, 0.98; P-trend = 0.04, P-interaction = 0.11). Carotenoid concentrations were strongly inversely associated with breast cancer recurrence and death (e.g., β-carotene top compared with bottom quintile RR: 0.32; 95% CI: 0.21, 0.51; P-trend < 0.001) compared with not recurrent and not lethal disease (P-heterogeneity < 0.001).
  
  
  CONCLUSIONS
  In this large prospective analysis with 20 y of follow-up, women with high plasma carotenoids were at reduced breast cancer risk particularly for more aggressive and ultimately fatal disease.
authors: From the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (AHE, XL, BR, RMT, SST, and SEH); the Departments of Epidemiology (AHE, XL, BR, RMT, SST, and SEH) and Biostatistics (XL and BR), Harvard T.H. Chan School of Public Health, Boston, MA; and the Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA (SEH). heather.eliassen@channing.harvard.edu.
authors: A Heather
authors: AH
authors: Eliassen
authors: From the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (AHE, XL, BR, RMT, SST, and SEH); the Departments of Epidemiology (AHE, XL, BR, RMT, SST, and SEH) and Biostatistics (XL and BR), Harvard T.H. Chan School of Public Health, Boston, MA; and the Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA (SEH).
authors: Xiaomei
authors: X
authors: Liao
authors: From the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (AHE, XL, BR, RMT, SST, and SEH); the Departments of Epidemiology (AHE, XL, BR, RMT, SST, and SEH) and Biostatistics (XL and BR), Harvard T.H. Chan School of Public Health, Boston, MA; and the Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA (SEH).
authors: Bernard
authors: B
authors: Rosner
authors: From the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (AHE, XL, BR, RMT, SST, and SEH); the Departments of Epidemiology (AHE, XL, BR, RMT, SST, and SEH) and Biostatistics (XL and BR), Harvard T.H. Chan School of Public Health, Boston, MA; and the Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA (SEH).
authors: Rulla M
authors: RM
authors: Tamimi
authors: From the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (AHE, XL, BR, RMT, SST, and SEH); the Departments of Epidemiology (AHE, XL, BR, RMT, SST, and SEH) and Biostatistics (XL and BR), Harvard T.H. Chan School of Public Health, Boston, MA; and the Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA (SEH).
authors: Shelley S
authors: SS
authors: Tworoger
authors: From the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (AHE, XL, BR, RMT, SST, and SEH); the Departments of Epidemiology (AHE, XL, BR, RMT, SST, and SEH) and Biostatistics (XL and BR), Harvard T.H. Chan School of Public Health, Boston, MA; and the Division of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA (SEH).
authors: Susan E
authors: SE
authors: Hankinson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology*; D002338:Carotenoids / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D005638:Fruit; D006801:Humans; D016015:Logistic Models; D000077276:Lycopene; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014675:Vegetables; D019207:beta Carotene / Q000097:blood*
chemical_list: D019207:beta Carotene; D002338:Carotenoids; C041635:alpha-carotene; D000077276:Lycopene
keywords: biomarkers; breast cancer; carotenoids; nested case-control study; plasma