Breast Cancer Molecular Subtypes and Supervised Analysis of Urinary Metal Mixtures in Mexican Women

Background: Breast cancer (BC) is not a single disease, but a set of molecular subtypes that could differ within their risk factors, which may include several metals. Our objective was to evaluate the association between BC molecular subtypes and metal mixtures, and to identify their main metal contributors within the mixture. Methods: The present report develops from our previous work based on a case–control study performed in Northern Mexico from 2007 to 2011. We included 498 population-based controls and 497 histologically confirmed BC cases. We gathered information about hormonal receptors (HR) and epidermal growth factor receptor 2 (HER2) from clinical records. Breast cancer molecular subtypes were determined as follow: HR + /HER2−, HER2 + or HR−/HER2− (TN). Urinary concentrations of ten metals were measured by inductively coupled plasma mass spectrometry. We used the weighted quantile sum (WQS) regression to obtain the metal mixtures, as well as to identify the main metal contributor within each mixture. Results: We found two weighted indices of metal mixtures contrastingly associated with BC molecular subtypes. One had tin as the main contributor and showed a positive association with BC (OR = 1.14 CI95% 1.10, 1.18), that remained only among HR + /HER2− subtype. The other weighted index was mainly determined by molybdenum followed by vanadium and cobalt. This second WQS index was negatively related to BC (OR = 0.78 CI95% 0.73, 0.83) regardless of its molecular subtypes. Conclusions: This work is among one of the first reports that provides evidence of associations between metal mixtures and BC, which are heterogenous according to BC molecular subtypes.