Exposure to Di-2-ethylhexyl phthalate and hormone receptor-positive breast cancer incidence.

10559 Background: Phthalates are ubiquitous environmental endocrine disruptors. As the predominant phthalate, di-2-ethylhexyl phthalate (DEHP) has been considered possibly carcinogenic to humans but large-scale longitudinal evidence is needed to further clarify its carcinogenicity. Up to date, no study have examined the in-situ DEHP exposure in breast cancer, in comparison with normal breast tissue or benign breast tumor.The present study aims to examine the association between DEHP exposure and incidence of hormone receptor-positive breast cancer (HR+BC) , both in a large cohort and in a group of patients whose in-situ DEHP exposure was analyzed. Methods: In 116,885 women of UK Biobank cohort, diagnosis of HR+BC was ascertained using general practitioner prescription records and information from National Health Service Cancer Registry and National Death Index. Baseline and yearly-average level of external DEHP exposure via water were estimated for each individual by linking chemical monitoring record of European Environment Agency with home address of the participants by Kriging interpolation model. We used Cox proportional hazards regression to estimate the association between DEHP exposure by water and risk of breast cancer. Furthermore, in-situ internal exposure level of DEHP in tumor tissue and normal breast tissue in 67 Chinese women with HR+BC or benign tumors was quantified using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), then binary Logistic regression was used to explore whether the in-situ DEHP level was higher in HR+BC compared to benign tumor or normal breast tissues. Results: In the UKB cohort women, during a median of 13.5 years follow up, the fourth quartile of baseline DEHP was associated with 1.20 fold risk of HR+BC (95% CI, 1.1 to1.4, P < 0.001). As for yearly-average exposure, each quartile of DEHP was positively associated with higher risk of HR+BC (HR, 1.12; 95% CI, 1.1 to 1.17, P trend < 0.001). The fourth quartile of yearly-average DEHP was associated with 1.52 fold risk of HR+BC (95% CI, 1.31 to 1.78, P < 0.001). No significant association was found between DEHP exposure and hormone receptor-negative breast cancer ( P = 0.294). In the Chinese women, the overall detection rate of DEHP (detected in any tissue type) in HR+BC women was significantly higher than in women with benign tumors (96.2% V.S. 7.1%, P < 0.001), and the detection rate of DEHP in breast cancer tissues was higher than in benign tumor tissue (55.7% V.S. 4.5%, P < 0.001). Logistic regression showed that breast cancer tissue was associated with a higher risk of DEHP contamination compared with benign tumor tissue (OR,11.77; 95% CI, 1.20 to 115.25, P = 0.034). Conclusions: Real-world level of DEHP exposure was associated with higher risk of HR+BC. The results may be crucial for effective and precise prevention of breast cancer.