Abstract

The association between phthalate exposure and breast cancer remains controversial. We performed a prospective patient cohort design to explore the interaction between creatinine-corrected urinary phthalate metabolites and hormone receptors as well as body mass index (BMI) on recurrent breast cancer. In this follow-up study, 636 female breast cancer patients and 45 new recurrent cases diagnosed for a total of 1576.68 person-years of follow-up were recruited. Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively associated with breast cancer recurrence, with adjusted hazard ratio (aHR) 3rd vs. 1st quartile of 0.15 (95% CI 0.04–0.51). The MEOHP presented as a non-monotonic dose–response (NMDR) curve, being U-shaped. In the stratification of hormone receptors, MEOHP still exhibited a U-shaped dose–response curve. The third quartile of MEOHP showed significant lowest recurrent risk in the status of ER-positive (aHR 0.18, 95% CI 0.05–0.66), PR-negative (aHR 0.14, 95% CI 0.03–0.63), and HER2-negative (aHR 0.24, 95% CI 0.08–0.76). Whether in BMI < 25 or in BMI ≥ 25, the third quartile of MEOHP was negatively associated with recurrent breast cancer, and there was a negative interaction on an additive scale between MEOHP and BMI (pinteraction = 0.042). The association between MEOHP and recurrent breast cancer was modified by hormone receptors and BMI.

Highlights

  • The association between phthalate exposure and breast cancer remains controversial

  • Seven hundred and twenty-six female patients diagnosed with breast cancer by breast surgeon specialists and histopathological sections were recruited from Kaohsiung Medical University (KMU) Chung-Ho Memorial Hospital from September 2013 to June 2018 and follow-up of these patients were continued until July 2019

  • This study is the first patient cohort design to explore the interaction between phthalate exposure and hormone receptors as well as body mass index (BMI) on recurrent breast cancer

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Summary

Introduction

We performed a prospective patient cohort design to explore the interaction between creatinine-corrected urinary phthalate metabolites and hormone receptors as well as body mass index (BMI) on recurrent breast cancer. In this follow-up study, 636 female breast cancer patients and 45 new recurrent cases diagnosed for a total of 1576.68 person-years of follow-up were recruited. Phthalates are known environmental endocrinedisrupting chemicals (EDCs) that could bind to and interact with ER and progesterone receptor (PR)[10,11]; the association of phthalates with hormone-dependent cancer, such as breast cancer, remains conflicting

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