Phthalate Exposure and Breast Cancer Incidence: A Danish Nationwide Cohort Study

• Type of Material: Article
• Authors: Thomas P. Ahern, University of Vermont; Anne Broe, University of Southern Denmark; Timothy Lash, Emory University; Deirdre P. Cronin-Fenton, Aarhus University Hospital; Sinna Pilgaard Ulrichsen, Aarhus University Hospital; Peer M. Christiansen, Aarhus University Hospital; Bernard F. Cole, University of Vermont; Rulla M. Tamimi, Brigham & Womens Hospital; Henrik Toft Sorensen, Aarhus University Hospital; Per Damkier, University of Southern Denmark
• Language: English
• Date: 2019-07-20
• Publisher: American Society of Clinical Oncology
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by American Society of Clinical Oncology.
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.18.02202
• Title of Journal or Parent Work: Journal of Clinical Oncology
• Volume: 37
• Issue: 21
• Start Page: 1800
• End Page: +
• Grant/Funding Information: Supported by Susan G. Komen for the Cure Grant No. CCR13264024 (T.P.A.), by funding from the National Institute of General Medical Sciences Grant No. P20 GM103644 (T.P.A.) and R01 CA166825 (T.L.L.).
• Keywords: Induce proliferation; Estrogenic; Civil registration system; Metabolites; Population; Nutrition examination survey; Science & Technology; Risk; Life Sciences & Biomedicine; Medications; Health; Oncology; Expression
• Research Categories: Health Sciences, Public Health; Health Sciences, Oncology; Health Sciences, Medicine and Surgery; Health Sciences, Nutrition

Abstract

PURPOSE Phthalate exposure is ubiquitous and especially high among users of drug products formulated with phthalates. Some phthalates mimic estradiol and may promote breast cancer. Existing epidemiologic studies on this topic are small, mostly not prospective, and have given inconsistent results. We estimated associations between longitudinal phthalate exposures and breast cancer risk in a Danish nationwide cohort, using redeemed prescriptions for phthalate-containing drug products to measure exposure. METHODS We ascertained the phthalate content of drugs marketed in Denmark using an internal Danish Medicines Agency ingredient database. We enrolled a Danish nationwide cohort of 1.12 million women at risk for a first cancer diagnosis on January 1, 2005. By combining drug ingredient data with the Danish National Prescription registry, we characterized annual, cumulative phthalate exposure through redeemed prescriptions. We then fit multivariable Cox regression models to estimate associations between phthalate exposures and incident invasive breast carcinoma according to tumor estrogen receptor status. RESULTS Over 9.99 million woman-years of follow-up, most phthalate exposures were not associated with breast cancer incidence. High-level dibutyl phthalate exposure (≥ 10,000 cumulative mg) was associated with an approximately two-fold increase in the rate of estrogen receptor–positive breast cancer (hazard ratio, 1.9; 95% CI, 1.1 to 3.5), consistent with in vitro evidence for an estrogenic effect of this compound. Lower levels of dibutyl phthalate exposure were not associated with breast cancer incidence. CONCLUSION Our results suggest that women should avoid high-level exposure to dibutyl phthalate, such as through long-term treatment with pharmaceuticals formulated with dibutyl phthalate.