What Medications Increase the Risk of Breast Cancer?

Long-term treatment with pharmaceuticals formulated with dibutyl phthalate can increase the risk of breast cancer, according to a study published in the Journal of Clinical Oncology.

The researchers assessed the phthalate content of 430 unique drug products from 29 phthalate-containing medications marketed in Denmark using an internal Danish Medicines Agency ingredient database. They enrolled a Danish nationwide cohort of 1.12 million women at risk for a first cancer diagnosis on January 1, 2005. The researchers characterized annual, cumulative phthalate exposure through redeemed prescriptions and estimated phthalate exposure and incident invasive breast carcinoma.

The study included more than 9.99 million woman-years of follow-up (median, 10 years). Women filled prescriptions for 204 of the unique drug products, representing 26 medications, with phthalate amounts ranging from 3 g to 150 mg per capsule.

About 14% of all women (n=161,737; median age, 58 years; range, 44-72 years) redeemed prescriptions for medications that contained phthalates compared with 86% (n=960,305; median age, 51 years; range, 40-63 years) who did not have phthalate exposure.

High levels of exposure associated with breast cancer risk

Women with medication-associated phthalate exposure appeared to be older, more likely to have comorbidities (20% vs. 10%), and to have used hormone therapy, cardiac glycosides, statins, and aspirin. There were 27,111 cases of invasive breast cancer, most of which (84%) were estrogen receptor (ER)-positive.

Most phthalate exposure was not associated with breast cancer incidence. However, high-level dibutyl phthalate exposure (≥10,000 cumulative mg) was associated with an approximately two-fold increase in the rate of ER+ breast cancer (hazard ratio = 1.9; 95% CI, 1.1-3.5), which is consistent with in vitro evidence for an estrogenic effect of this compound, the authors noted. Lower levels of dibutyl phthalate exposure were not associated with breast cancer.