In the Journals

Certain medications linked to increased breast cancer risk

Women with high cumulative exposure to dibutyl phthalate through medications appeared to be at increased risk for ER-positive breast cancer, according to results of a retrospective study published in Journal of Clinical Oncology.

“Phthalates are potential endocrine disruptors — exogenous compounds that mimic hormones and may therefore affect fertility, fetal/child development and some cancers,” Thomas P. Ahern, PhD, MPH, assistant professor in the department of surgery at University of Vermont, and colleagues wrote. “Preclinical evidence suggests that some phthalates promote breast tumor growth through ER signaling. Estrogen-independent breast cancer promotion mechanisms have also been reported for phthalates, as have antiestrogenic effects.”

Products containing phthalates include medical supplies, pharmaceutical capsules, food containers, cosmetics and toys.

Ahern and colleagues studied the association between long-term phthalate exposure and the risk for breast cancer among a Danish nationwide cohort of 1,122,042 women at risk for a first cancer diagnosis in 2005.

Researchers identified 430 unique drug products from 29 phthalate-containing medications, and combined drug ingredient data with the Danish National Prescription registry to determine annual and cumulative phthalate exposure through redeemed prescriptions.

Women in the cohort filled prescriptions for 204 of the unique drug products, representing 26 medications. Phthalate amounts ranged from 3 g to 150 mg per capsule.

About 14% of all women (n = 161,737; median age, 58 years; range, 44-72) redeemed prescriptions for medications that contained phthalates, compared with 86% (n = 960,305; median age, 51 years; range, 40-63) with no phthalate exposure. In addition to being older, women with medication-associated phthalate exposure appeared more likely to have comorbidities (20% vs. 10%) and to have used hormone therapy, cardiac glycosides, statins and aspirin.

Results showed 27,111 cases of invasive breast cancer (84% ER-positive) among the cohort during 9.99 million woman-years of follow-up (median, 10 years).

Most phthalate exposures did not appear associated with incidence of breast cancer. However, the rate of ER-positive disease among women with the highest cumulative exposure to dibutyl phthalate ( 10,000 mg) was nearly two times higher than that of women with no exposure (HR = 1.9; 95% CI, 1.1-3.5).

Researchers observed no association between lower levels of exposure and breast cancer incidence.

Researchers could not adjust for adiposity or reproductive history; however, these limitations did not have a substantial impact on association estimates, according to researchers.

“Butyl benzyl phthalate and diethylhexyl phthalate have similar actions to dibutyl phthalate in vitro but could not be measured via medication use in Denmark,” Ahern and colleagues wrote. “Future efforts should focus on these potentially important exposures in addition to replicating the dibutyl phthalate association. In the meantime, it may be prudent for women to consult with prescribers and pharmacists to determine the phthalate content of their medications and whether long-term treatment with dibutyl phthalate-formulated pharmaceuticals can be avoided.”

The impact of the findings, if confirmed in future studies, depends on whether the drugs can be exchanged for comparable formulations without phthalates, Elizabeth D. Kantor, PhD, MPH, assistant attending epidemiologist at Memorial Sloan Kettering Cancer Center, and Megan E. Romano, PhD, MPH, assistant professor of epidemiology at Dartmouth College, wrote in an accompanying editorial.

“Understanding the exchangeability of these drugs speaks to the potential for residual confounding within active comparator analyses as well as policy implications and contraindications of use, as well as safety of the phthalate-containing vs. nonphthalate-containing options,” Kantor and Romano wrote. – by John DeRosier

Disclosure s : Ahern reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Kantor and Romano report no relevant financial disclosures.

Women with high cumulative exposure to dibutyl phthalate through medications appeared to be at increased risk for ER-positive breast cancer, according to results of a retrospective study published in Journal of Clinical Oncology.

“Phthalates are potential endocrine disruptors — exogenous compounds that mimic hormones and may therefore affect fertility, fetal/child development and some cancers,” Thomas P. Ahern, PhD, MPH, assistant professor in the department of surgery at University of Vermont, and colleagues wrote. “Preclinical evidence suggests that some phthalates promote breast tumor growth through ER signaling. Estrogen-independent breast cancer promotion mechanisms have also been reported for phthalates, as have antiestrogenic effects.”

Products containing phthalates include medical supplies, pharmaceutical capsules, food containers, cosmetics and toys.

Ahern and colleagues studied the association between long-term phthalate exposure and the risk for breast cancer among a Danish nationwide cohort of 1,122,042 women at risk for a first cancer diagnosis in 2005.

Researchers identified 430 unique drug products from 29 phthalate-containing medications, and combined drug ingredient data with the Danish National Prescription registry to determine annual and cumulative phthalate exposure through redeemed prescriptions.

Women in the cohort filled prescriptions for 204 of the unique drug products, representing 26 medications. Phthalate amounts ranged from 3 g to 150 mg per capsule.

About 14% of all women (n = 161,737; median age, 58 years; range, 44-72) redeemed prescriptions for medications that contained phthalates, compared with 86% (n = 960,305; median age, 51 years; range, 40-63) with no phthalate exposure. In addition to being older, women with medication-associated phthalate exposure appeared more likely to have comorbidities (20% vs. 10%) and to have used hormone therapy, cardiac glycosides, statins and aspirin.

Results showed 27,111 cases of invasive breast cancer (84% ER-positive) among the cohort during 9.99 million woman-years of follow-up (median, 10 years).

Most phthalate exposures did not appear associated with incidence of breast cancer. However, the rate of ER-positive disease among women with the highest cumulative exposure to dibutyl phthalate ( 10,000 mg) was nearly two times higher than that of women with no exposure (HR = 1.9; 95% CI, 1.1-3.5).

Researchers observed no association between lower levels of exposure and breast cancer incidence.

Researchers could not adjust for adiposity or reproductive history; however, these limitations did not have a substantial impact on association estimates, according to researchers.

“Butyl benzyl phthalate and diethylhexyl phthalate have similar actions to dibutyl phthalate in vitro but could not be measured via medication use in Denmark,” Ahern and colleagues wrote. “Future efforts should focus on these potentially important exposures in addition to replicating the dibutyl phthalate association. In the meantime, it may be prudent for women to consult with prescribers and pharmacists to determine the phthalate content of their medications and whether long-term treatment with dibutyl phthalate-formulated pharmaceuticals can be avoided.”

PAGE BREAK

The impact of the findings, if confirmed in future studies, depends on whether the drugs can be exchanged for comparable formulations without phthalates, Elizabeth D. Kantor, PhD, MPH, assistant attending epidemiologist at Memorial Sloan Kettering Cancer Center, and Megan E. Romano, PhD, MPH, assistant professor of epidemiology at Dartmouth College, wrote in an accompanying editorial.

“Understanding the exchangeability of these drugs speaks to the potential for residual confounding within active comparator analyses as well as policy implications and contraindications of use, as well as safety of the phthalate-containing vs. nonphthalate-containing options,” Kantor and Romano wrote. – by John DeRosier

Disclosure s : Ahern reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Kantor and Romano report no relevant financial disclosures.