Breast cancer immunophenotypes and serum organochlorine pesticides in Mexican women: Mixture exposure approach

Epidemiological studies on associations between breast cancer (BC) and organochlorine pesticides (OCP) are inconclusive. The majority of studies have evaluated the effect of single compounds without considering multiple OCP exposures and immunophenotypes of BC. We aimed to evaluate the association between BC immunophenotypes and serum OCP mixtures, and identify the main contributors within mixtures. We included 767 histopathologically confirmed incident BC cases and 908 controls from a population-based case-control study conducted from 2007 to 2011 in Northern Mexico. We obtained direct information about sociodemographic, lifestyle and reproductive characteristics. We collected data from clinical records about hormonal receptors (HR) and epidermal growth factor receptor 2 (HER2) expressions. Immunophenotypes were determined as HR+/ HER2-, HER2+ or HR-/HER2-. We quantified OCP and metabolites by gas chromatography using an electron capture micro detector. We used Weighted Quantile Sum regression to assess the association of BC and exposure to multiple OCP, and their contribution within the mixture. We found a positive adjusted association between BC and an OCP mixture (OR: 3.48, 95%CI: 2.58, 4.69), whose primary contribution arose from the isomers of hexachlorocyclohexane and endosulfan, as well as endosulfan sulfate. We also identified a mixture negatively associated (OR: 0.13, 95%CI: 0.08, 0.20), characterized by p,p'-DDT and chlordane metabolites. All these associations remained regardless BC immunophenotypes. This is the first epidemiological report that identified serum OCP mixtures associated with BC immunophenotypes. Due to OCP ubiquity, biomagnification, and continuous exposure, they constitute a global problem of persistent exposure that might be related to BC risk.