Breast Cancer Research and Treatment

, Volume 158, Issue 1, pp 149–155 | Cite as

Plasma fluorescent oxidation products and risk of estrogen receptor-negative breast cancer in the Nurses’ Health Study and Nurses’ Health Study II

  • Kelly A. HirkoEmail author
  • Renée T. Fortner
  • Susan E. Hankinson
  • Tianying Wu
  • A. Heather Eliassen


Findings from epidemiologic studies of oxidative stress biomarkers and breast cancer have been mixed, although no studies have focused on estrogen receptor-negative (ER−) tumors which may be more strongly associated with oxidative stress. We examined prediagnostic plasma fluorescent oxidation products (FlOP), a global biomarker of oxidative stress, and risk of ER− breast cancer in a nested case-control study in the Nurses’ Health Study and Nurses’ Health Study II. ER− breast cancer cases (n = 355) were matched to 355 controls on age, month/time of day of blood collection, fasting status, menopausal status, and menopausal hormone use. Conditional logistic regression models were used to examine associations of plasma FlOP at three emission wavelengths (FlOP_360, FlOP_320, and FlOP_400) and risk of ER− breast cancer. We did not observe any significant associations between FlOP measures and risk of ER− breast cancer overall; the RRQ4vsQ1 (95 %CI) 0.70 (0.43–1.13), p trend = 0.09 for FlOP_360; 0.91(0.56-1.46), p trend = 0.93 for FlOP_320; and 0.62 (0.37-1.03), p trend = 0.10 for FlOP_400. Results were similar in models additionally adjusted for total carotenoid levels and in models stratified by age and total carotenoids. Although high (vs. low) levels of FIOP_360 and FIOP_400 were associated with lower risk of ER− breast cancer in lean women (body mass index (BMI) < 25 kg/m2) but not in overweight/obese women, these differences were not statistically significant (pint = 0.23 for FlOP_360; pint = 0.37 for FlOP_400). Our findings suggest that positive associations of plasma FlOP concentrations and ER− breast cancer risk are unlikely.


Fluorescent oxidation products Oxidative stress Breast cancer Estrogen receptor 



This research was supported from the NIH RO1 CA131218, NHS and NHSII UM1: CA186107 and CA176726. KA Hirko was supported by the R25 CA098566 and the T32 CA009001 training grants. RT Fortner was supported by the T32 CA009001 training grant. We would like to thank the participants and staff of the Nurses’ Health Study and the Nurses’ Health Study II for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflicts of interest. The analysis presented here complies with current laws of the country in which they were performed.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Epidemiology and Biostatistics, College of Human MedicineMichigan State UniversityEast LansingUSA
  2. 2.Division of Cancer EpidemiologyGerman Cancer Research Center (DKFZ)HeidelbergGermany
  3. 3.Channing Division of Network Medicine, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  4. 4.Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonUSA
  5. 5.Department of Biostatistics and EpidemiologyUniversity of MassachusettsAmherstUSA
  6. 6.Division of Biostatistics and Epidemiology Department of Environmental HealthUniversity of CincinnatiCincinnatiUSA

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