Cadmium Exposure and Risk of Breast Cancer by Histological and Tumor Receptor Subtype in White Caucasian Women: A Hospital-Based Case-Control Study

Abstract

As the majority of experimental studies suggest cadmium being metalloestrogen, we examined cadmium/breast cancer (BC) association by histological and tumor receptor subtype in 509 invasive BC patients and 1170 controls. Urinary cadmium was determined by atomic absorption spectrometry, and categorized using tertiles of its distribution in the controls: <0.18, 0.18–0.33, >0.33 kg × 10−9/kg × 10−3 creatinine. Relative to the lowest category of urinary cadmium adjusted odds ratio (OR) of ductal BC was 1.18 (95% confidence interval (CI): 0.89–1.58) in the intermediate and 1.53 (95% CI: 1.15–2.04) in the highest category. There was a significant association for hormone receptor-positive ductal BC: ORs per category increase were 1.34 (95% CI: 1.14–1.59) for estrogen receptor-positive (ER+), 1.33 (95% CI: 1.09–1.61) for progesterone receptor-positive (PR+) and 1.35 (95% CI: 1.11–1.65) for ER+/PR+ BC. We found a significant association between cadmium and human epidermal growth factor receptor 2-negative (HER2−) ductal BC. The strongest association with cadmium was for ER+/PR+/HER2− ductal BC. The associations between cadmium and lobular BC with hormone receptor-positive and HER2− were positive but insignificant. There was no evidence that the associations with cadmium differed for cancers with different tumor histology (p-heterogeneity > 0.05). This study provides evidence that urinary cadmium is associated with the risk of hormone receptor-positive and HER2− breast cancer independent of tumor histology.

Exposure to airborne cadmium and breast cancer stage, grade and histology at diagnosis: findings from the E3N cohort study

“…Only one study has assessed the association between cadmium and risk of BC by histological subtype, and found an increased risk of ductal BC with an adjusted OR of 1.1 (95% CI 0.89–1.58) in the intermediate and 1.53 (95% CI 1.15–2.04) in the highest category of urinary cadmium as compared to the lowest tertile. However this study did not investigate tubular BC 38 .…”

Exposure to airborne cadmium and breast cancer stage, grade and histology at diagnosis: Findings from the E3N cohort study

“…Only one study has assessed the association between cadmium and risk of BC by histological subtype, reporting an increased risk of ductal BC with an adjusted OR of 1.18 (95% CI: 0.89-1.58) in the intermediate and 1.53 (95% CI: 1.15-2.04) in the highest category of urinary cadmium as compared to the lowest tertile. However this study did not investigate tubular BC [50].…”

Unravelling the chemical exposome in cohort studies: routes explored and steps to become comprehensive

“…The study designs included cross-sectional surveys, longitudinal cohort studies, and interventional trials with an age range from 0 to > 80 years with sample sizes from 30 to 14,000 participants [ 50 , 112 ]. While HELIX focused on childhood with the inclusion of birth-cohorts [ 104 ], HEALS, EXPOsOMICS, and HBM4EU cover the entire life span with a stronger focus on adulthood [ 93 , 94 , 98 ]. The gender ratio across the majority of studies is balanced with exceptions that focus on females [ 62 , 94 ].…”

“…While HELIX focused on childhood with the inclusion of birth-cohorts [ 104 ], HEALS, EXPOsOMICS, and HBM4EU cover the entire life span with a stronger focus on adulthood [ 93 , 94 , 98 ]. The gender ratio across the majority of studies is balanced with exceptions that focus on females [ 62 , 94 ]. Another relevant aspect is the respective time of enrollment, which starts as early as the 1990s (e.g.…”

“…HBM4EU, which is the most recent of the described projects, has, so far, resulted in one publication that addressed breast cancer in a sample of 585 females (age 28–85 years), who were enrolled between 2007 and 2011 [ 94 ]. A further review and the projects overall ambition promise that further work will follow [ 1 ].…”