Phthalate exposure and breast cancer incidence

A danish nationwide cohort study

Thomas P. Ahern*, Anne Broe, Timothy L. Lash, Deirdre P. Cronin-Fenton, Sinna Pilgaard Ulrichsen, Peer M. Christiansen, Bernard F. Cole, Rulla M. Tamimi, Henrik Toft Sørensen, Per Damkier

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalJournal of Clinical Oncology
Volume37
Issue number21
Pages (from-to)1800-1809
ISSN0732-183X
DOIs
Publication statusPublished - 20. Jul 2019

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Cohort Studies
Dibutyl Phthalate
Incidence
Prescriptions
Pharmaceutical Preparations
Estrogens
phthalic acid
Denmark
Internal Medicine
Drug Users
Proportional Hazards Models
Registries
Epidemiologic Studies
Neoplasms
Databases

Cite this

Ahern, T. P., Broe, A., Lash, T. L., Cronin-Fenton, D. P., Ulrichsen, S. P., Christiansen, P. M., ... Damkier, P. (2019). Phthalate exposure and breast cancer incidence: A danish nationwide cohort study. Journal of Clinical Oncology, 37(21), 1800-1809. https://doi.org/10.1200/JCO.18.02202
Ahern, Thomas P. ; Broe, Anne ; Lash, Timothy L. ; Cronin-Fenton, Deirdre P. ; Ulrichsen, Sinna Pilgaard ; Christiansen, Peer M. ; Cole, Bernard F. ; Tamimi, Rulla M. ; Sørensen, Henrik Toft ; Damkier, Per. / Phthalate exposure and breast cancer incidence : A danish nationwide cohort study. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 21. pp. 1800-1809.
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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.",
author = "Ahern, {Thomas P.} and Anne Broe and Lash, {Timothy L.} and Cronin-Fenton, {Deirdre P.} and Ulrichsen, {Sinna Pilgaard} and Christiansen, {Peer M.} and Cole, {Bernard F.} and Tamimi, {Rulla M.} and S{\o}rensen, {Henrik Toft} and Per Damkier",
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Ahern, TP, Broe, A, Lash, TL, Cronin-Fenton, DP, Ulrichsen, SP, Christiansen, PM, Cole, BF, Tamimi, RM, Sørensen, HT & Damkier, P 2019, 'Phthalate exposure and breast cancer incidence: A danish nationwide cohort study', Journal of Clinical Oncology, vol. 37, no. 21, pp. 1800-1809. https://doi.org/10.1200/JCO.18.02202

Phthalate exposure and breast cancer incidence : A danish nationwide cohort study. / Ahern, Thomas P.; Broe, Anne; Lash, Timothy L.; Cronin-Fenton, Deirdre P.; Ulrichsen, Sinna Pilgaard; Christiansen, Peer M.; Cole, Bernard F.; Tamimi, Rulla M.; Sørensen, Henrik Toft; Damkier, Per.

In: Journal of Clinical Oncology, Vol. 37, No. 21, 20.07.2019, p. 1800-1809.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Phthalate exposure and breast cancer incidence

T2 - A danish nationwide cohort study

AU - Ahern, Thomas P.

AU - Broe, Anne

AU - Lash, Timothy L.

AU - Cronin-Fenton, Deirdre P.

AU - Ulrichsen, Sinna Pilgaard

AU - Christiansen, Peer M.

AU - Cole, Bernard F.

AU - Tamimi, Rulla M.

AU - Sørensen, Henrik Toft

AU - Damkier, Per

PY - 2019/7/20

Y1 - 2019/7/20

N2 - 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.

AB - 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.

U2 - 10.1200/JCO.18.02202

DO - 10.1200/JCO.18.02202

M3 - Journal article

VL - 37

SP - 1800

EP - 1809

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 21

ER -

Ahern TP, Broe A, Lash TL, Cronin-Fenton DP, Ulrichsen SP, Christiansen PM et al. Phthalate exposure and breast cancer incidence: A danish nationwide cohort study. Journal of Clinical Oncology. 2019 Jul 20;37(21):1800-1809. https://doi.org/10.1200/JCO.18.02202