Study Specifics1

Dr Reeves’ group conducted a nested case-control study within the WHI prospective cohort (419 invasive cases and 838 controls). Controls were matched 2:1 to cases on age, enrollment date, follow-up time, and WHI study group. The group quantified 13 phthalate metabolites and creatinine in 2 or 3 urine samples per participant over 1 to 3 years

In general, phthalate biomarker concentrations were not associated with an increase in breast cancer risk, either overall or by disease subtype. Further, phthalate biomarker concentrations exhibited within-person variability during a 3-year period, reinforcing the idea that a single urine sample may be insufficient to characterize exposure. 

Continue Reading

Because humans are “really good at metabolizing and excreting phthalates through urine,” within 12 to 24 hours, half the chemical has typically been excreted from the body, Dr Reeves said. Therefore, having up to 3 measurements available for analysis at varying time points over 3 years on each person was considered a significant advantage of the study, Dr Reeves said. 

Clinical Implications

Avoiding (or reducing) exposure to phthalates is recommended, but lifestyle modifications like maintaining a healthy weight, increasing physical activity, and limiting alcohol consumption “are modifications that have solid evidence of reducing cancer risk,” Dr Reeves said. “Doing those would be advisable, reducing exposure to phthalates is reasonable, but the data just aren’t as solid right now [and] that makes a difference.”

Related Articles

Authors of a review on the topic came to similar conclusions, noting, “epidemiological studies performed so far have not established any definite correlation between exposure to the various phthalates and the risk of breast cancer.”2

Phthalate exposure has increased since the 1990s when the WHI started enrolling women, but some phthalates have also been phased out (such as DEHP, DBP, DIBP, and BBP) while others have been phased into manufacturing processes.

It’s another reason Dr Reeves said the study results are not definitive (as her group did not evaluate phthalates that were not available in the 1990s).

Moving forward, Dr Reeves and colleagues are evaluating alternative approaches to studying links between endocrine-disrupting chemicals and breast cancer, including evaluating intermediate markers of breast cancer risk.


  1. Reeves KW, Santana MD, Manson JE, et al. Phthalate biomarker concentrations and postmenopausal breast cancer risk [published online January 10, 2019]. J Natl Cancer Inst. doi: 10.1093/jnci/djz002
  2. Zuccarello P, Oliveri Conti G, Cavallaro F, et al. Implication of dietary phthalates in breast cancer. A systematic review. Food Chem Toxicol. 2018;118:667–674. 
  3. Breast Cancer Prevention Partners. Phthalates. Accessed February 21, 2019.