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J Natl Cancer Inst. 2019 Jan 10. doi: 10.1093/jnci/djz002. [Epub ahead of print]

Urinary Phthalate Biomarker Concentrations and Postmenopausal Breast Cancer Risk.

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Department of Biostatistics and Epidemiology, University of Massachusetts Amherst, Amherst, MA.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, and the Harvard T.H. Chan School of Public Health, Boston, MA.
Department of Biology, University of Massachusetts Amherst, Amherst, MA.
Department of Biostatistics, Yale School of Public Health, New Haven, CT.
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA.
Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington, IN.
Department of Ob/Gyn, Stanford University School of Medicine, Stanford, CA.
Program in Public Health, Department of Family, Population, & Preventive Medicine, Stony Brook University, Stony Brook, NY.
Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, NY.
Department of Oncology, School of Medicine, Wayne State University, and the Karmanos Cancer Institute, Detroit, MI.
Department of Epidemiology, Colleges of Medicine and Public Health and Health Professions, University of Florida, Gainesville, FL.
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA.



Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking.


We conducted a nested case-control study within the Women's Health Initiative (WHI) prospective cohort (Nā€‰=ā€‰419 invasive cases and 838 controls). Controls were matched 2:1 to cases on age, enrollment date, follow-up time, and WHI study group. We quantified thirteen phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios and 95% confidence intervals (OR, 95% CI) for breast cancer risk associated with each phthalate biomarker over up to 19 years of follow-up.


Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (e.g. 4th vs 1st quartile of diethylhexyl phthalate OR 1.03, 95% CI 0.91 - 1.17). Results were generally similar in analyses restricted to disease subtypes, to non-users of postmenopausal hormone therapy, stratified by body mass index, or to cases diagnosed within three, five, or ten years.


In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer.


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