Cancer Causes & Control

, Volume 26, Issue 9, pp 1233–1244 | Cite as

Plasma carotenoids and breast cancer risk in the Cancer Prevention Study II Nutrition Cohort

  • Ying WangEmail author
  • Susan M. Gapstur
  • Mia M. Gaudet
  • Jeremy D. Furtado
  • Hannia Campos
  • Marjorie L. McCullough
Original paper



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.


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).


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).


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


Plasma carotenoids Breast cancer Estrogen receptor Cohort study Body mass index Smoking 



The American Cancer Society funds the creation, maintenance, and updating of the Cancer Prevention Study II (CPS-II) cohort. We thank the CPS-II participants and Study Management Group for their invaluable contributions to this research. We also acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention National Program of Cancer Registries, as well as cancer registries supported by the National Cancer Institute Surveillance Epidemiology and End Results program.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10552_2015_614_MOESM1_ESM.docx (23 kb)
Supplementary material 1 (DOCX 23 kb)


  1. 1.
    Maiani G, Caston MJ, Catasta G et al (2009) Carotenoids: actual knowledge on food sources, intakes, stability and bioavailability and their protective role in humans. Mol Nutr Food Res 53(Suppl 2):S194–S218CrossRefPubMedGoogle Scholar
  2. 2.
    Hozawa A, Jacobs DR Jr, Steffes MW, Gross MD, Steffen LM, Lee DH (2007) Relationships of circulating carotenoid concentrations with several markers of inflammation, oxidative stress, and endothelial dysfunction: the Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) study. Clin Chem 53:447–455PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49:1603–1616PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Tang XH, Gudas LJ (2011) Retinoids, retinoic acid receptors, and cancer. Annu Rev Pathol 6:345–364CrossRefPubMedGoogle Scholar
  5. 5.
    Hu F, Wang Yi B, Zhang W et al (2012) Carotenoids and breast cancer risk: a meta-analysis and meta-regression. Breast Cancer Res Treat 131:239–253CrossRefPubMedGoogle Scholar
  6. 6.
    Zhang X, Spiegelman D, Baglietto L et al (2012) Carotenoid intakes and risk of breast cancer defined by estrogen receptor and progesterone receptor status: a pooled analysis of 18 prospective cohort studies. Am J Clin Nutr 95:713–725PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Aune D, Chan DS, Vieira AR et al (2012) Fruits, vegetables and breast cancer risk: a systematic review and meta-analysis of prospective studies. Breast Cancer Res Treat 134:479–493CrossRefPubMedGoogle Scholar
  8. 8.
    Jung S, Spiegelman D, Baglietto L et al (2013) Fruit and vegetable intake and risk of breast cancer by hormone receptor status. J Natl Cancer Inst 105:219–236PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Aune D, Chan DS, Vieira AR et al (2012) Dietary compared with blood concentrations of carotenoids and breast cancer risk: a systematic review and meta-analysis of prospective studies. Am J Clin Nutr 96:356–373CrossRefPubMedGoogle Scholar
  10. 10.
    Eliassen AH, Hendrickson SJ, Brinton LA et al (2012) Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies. J Natl Cancer Inst 104:1905–1916PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Wallstrom P, Wirfalt E, Lahmann PH, Gullberg B, Janzon L, Berglund G (2001) Serum concentrations of beta-carotene and alpha-tocopherol are associated with diet, smoking, and general and central adiposity. Am J Clin Nutr 73:777–785PubMedGoogle Scholar
  12. 12.
    Stryker WS, Kaplan LA, Stein EA, Stampfer MJ, Sober A, Willett WC (1988) The relation of diet, cigarette smoking, and alcohol consumption to plasma beta-carotene and alpha-tocopherol levels. Am J Epidemiol 127:283–296PubMedGoogle Scholar
  13. 13.
    Calle EE, Rodriguez C, Jacobs EJ et al (2002) The American Cancer Society Cancer Prevention Study II Nutrition Cohort: rationale, study design, and baseline characteristics. Cancer 94:2490–2501CrossRefPubMedGoogle Scholar
  14. 14.
    El-Sohemy A, Baylin A, Kabagambe E, Ascherio A, Spiegelman D, Campos H (2002) Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake. Am J Clin Nutr 76:172–179PubMedGoogle Scholar
  15. 15.
    Holden JM, Eldridge AL, Beecher GR et al (1999) Carotenoid content of US foods: an update of the database. J Food Compos Anal 12:169–196Google Scholar
  16. 16.
    Willett W, Stampfer MJ (1986) Total energy intake: implications for epidemiologic analyses. Am J Epidemiol 124:17–27PubMedGoogle Scholar
  17. 17.
    Wang M, Kuchiba A, Ogino S (2015) A meta-regression method for studying etiologic heterogeneity across disease subtypes classified by multiple biomarkers. Am J Epidemiol (in press)Google Scholar
  18. 18.
    Kleinbaum DG, Kupper LL, Muller KE (2007) Applied regression analysis and other multivariable methods. Cengage Learning, BelmontGoogle Scholar
  19. 19.
    Dorgan JF, Sowell A, Swanson CA et al (1998) Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States). Cancer Causes Control 9:89–97CrossRefPubMedGoogle Scholar
  20. 20.
    Hulten K, Van Kappel AL, Winkvist A et al (2001) Carotenoids, alpha-tocopherols, and retinol in plasma and breast cancer risk in northern Sweden. Cancer Causes Control 12:529–537CrossRefPubMedGoogle Scholar
  21. 21.
    Toniolo P, Van Kappel AL, Akhmedkhanov A et al (2001) Serum carotenoids and breast cancer. Am J Epidemiol 153:1142–1147CrossRefPubMedGoogle Scholar
  22. 22.
    Sato R, Helzlsouer KJ, Alberg AJ, Hoffman SC, Norkus EP, Comstock GW (2002) Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 11:451–457PubMedGoogle Scholar
  23. 23.
    Tamimi RM, Hankinson SE, Campos H et al (2005) Plasma carotenoids, retinol, and tocopherols and risk of breast cancer. Am J Epidemiol 161:153–160CrossRefPubMedGoogle Scholar
  24. 24.
    Sesso HD, Buring JE, Zhang SM, Norkus EP, Gaziano JM (2005) Dietary and plasma lycopene and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 14:1074–1081CrossRefPubMedGoogle Scholar
  25. 25.
    Dorjgochoo T, Gao YT, Chow WH et al (2009) Plasma carotenoids, tocopherols, retinol and breast cancer risk: results from the Shanghai Women Health Study (SWHS). Breast Cancer Res Treat 117:381–389PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Epplein M, Shvetsov YB, Wilkens LR et al (2009) Plasma carotenoids, retinol, and tocopherols and postmenopausal breast cancer risk in the Multiethnic Cohort Study: a nested case–control study. Breast Cancer Res 11:R49PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Kabat GC, Kim M, Adams-Campbell LL et al (2009) Longitudinal study of serum carotenoid, retinol, and tocopherol concentrations in relation to breast cancer risk among postmenopausal women. Am J Clin Nutr 90:162–169PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Maillard V, Kuriki K, Lefebvre B et al (2010) Serum carotenoid, tocopherol and retinol concentrations and breast cancer risk in the E3N-EPIC study. Int J Cancer 127:1188–1196CrossRefPubMedGoogle Scholar
  29. 29.
    Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 109:1721–1728CrossRefPubMedGoogle Scholar
  30. 30.
    Gaudet MM, Gapstur SM, Sun J, Diver WR, Hannan LM, Thun MJ (2013) Active smoking and breast cancer risk: original cohort data and meta-analysis. J Natl Cancer Inst 105:515–525CrossRefPubMedGoogle Scholar
  31. 31.
    Marangon K, Herbeth B, Lecomte E et al (1998) Diet, antioxidant status, and smoking habits in French men. Am J Clin Nutr 67:231–239PubMedGoogle Scholar
  32. 32.
    Ross MA, Crosley LK, Brown KM et al (1995) Plasma concentrations of carotenoids and antioxidant vitamins in Scottish males: influences of smoking. Eur J Clin Nutr 49:861–865PubMedGoogle Scholar
  33. 33.
    Albanes D, Virtamo J, Taylor PR, Rautalahti M, Pietinen P, Heinonen OP (1997) Effects of supplemental beta-carotene, cigarette smoking, and alcohol consumption on serum carotenoids in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Am J Clin Nutr 66:366–372PubMedGoogle Scholar
  34. 34.
    Heinonen OP, Albanes D (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The alpha-tocopherol, beta carotene cancer prevention study group. N Engl J Med 330:1029–1035Google Scholar
  35. 35.
    Omenn GS, Goodman GE, Thornquist MD et al (1996) Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 334:1150–1155CrossRefPubMedGoogle Scholar
  36. 36.
    Pradhan AD, Manson JE, Rossouw JE et al (2002) Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women’s Health Initiative observational study. JAMA 288:980–987CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Ying Wang
    • 1
    Email author
  • Susan M. Gapstur
    • 1
  • Mia M. Gaudet
    • 1
  • Jeremy D. Furtado
    • 2
  • Hannia Campos
    • 2
  • Marjorie L. McCullough
    • 1
  1. 1.Epidemiology Research ProgramAmerican Cancer SocietyAtlantaUSA
  2. 2.Department of NutritionHarvard School of Public HealthBostonUSA

Personalised recommendations