Abstract P5-08-11: Urinary arsenic metabolites and risk of breast cancer molecular subtypes in northern Mexican women
Authors: López-Carrillo L , Gamboa-Loira B , Cebrián ME 
Published: March 2017

Abstract
Background/Aim: For many years, the presence of arsenic (As) in drinking water of some areas in Northern Mexico has been a major concern. As levels have ranged from 71 to 600 μg/L. We have recently reported that women residing in Northern Mexico, with higher urinary monomethyl arsenic acid percentage (%MMA) had an increased breast cancer (BC) risk (MMA% ORQ5vs.Q1=2.63; 95%CI: 1.89, 3.66; p for trend &lt;0.001) (López-Carrillo et al., 214).
Breast tumor subtypes with distinctive biology and treatment responses are defined by the immunohistochemical expression of estrogen and progesterone receptors (HR) and human epidermal growth factor receptor 2 (HER2). Epidemiological evidence suggests that BC risk factors (i.e. breastfeeding, parity, menarche, etc.) may vary by tumor pathology.We assessed if %MMA is associated with a particular BC molecular subtype.
Methods: A population based case–control study was performed from 2007 to 2011 in five states of Northern Mexico. Incident cases were identified from main public tertiary hospitals in the study area. A total of 499 patients with histopathologically confirmed BC and molecular subtype status available information were identified. Controls were healthy women, with no history of cancer, matched 1:1 by age.
Tumor marker information for estrogen receptor (ER), progesterone receptor (PR) and HER2 was obtained from medical records. ER+ and PR+ was based on &gt;=1% cell staining. HER2+ status was determined when at least 30% of protein overexpression was observed in the tumor cell. Cases were assigned to one of three tumor marker categories: HR+ (ER+ and/or PR+ and HER2-), HER+ (regardless of ER or PR status) and TNBC (ER-, PR-, and HER2-).
Urinary concentrations (μg/L) of species As3+, As5+, MMA5+, DMA5+, and arsenobetaine (AsB) were determined by high-performance liquid chromatography ICP-MS. Detection limits were As3+: 0.12; As5+: 0.20; MMA5+: 0.12; DMA5+: 0.08; AsB: 0.08. Results were reported by g of creatinine. Total As was calculated by using both the sum of iAs, MMA, DMA plus or minus AsB concentration (TAs or TAs-AsB, respectively). iAs was calculated as the sum of trivalent (As3+) and pentavalent (As5+). %iAs, %MMA and %DMA species were estimated using TAs-AsB as denominator.
Using logistic regression models, the associations between BC molecular subtypes and MMA% and DMA% was estimated according to the observed quintile distribution among controls. Based on the median value of each quintile a lineal trend was assessed accordingly.
Results.The mean age of cases and controls was around 54 years with 51 years of residence in the study zone. In the entire population, TAs ranged from 0.47 to 303.29 μg/L (0.45 to 1683.83 μg/g creatinine). HR+ BC patients were 57%, HER2 23% and TNBC 20%. These figures are similar to those reported among other groups of Mexican cancer patients. After controlling by key BC factors, %MMA remained as a significant risk factor for BC only for HR+. HER2+ and TNBC tumors were not significantly associated with urinary As metabolites.
Conclusion: Our results suggest that increased BC risk related to As exposure is not mediated by HER2 expression. This is the first report on As exposure and breast cancer subtypes which requires further confirmation.
Citation Format: López-Carrillo L, Gamboa-Loira B, Cebrián ME. Urinary arsenic metabolites and risk of breast cancer molecular subtypes in northern Mexican women [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-08-11.