Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. 
Clinical Pharmacist and Master’s student in Clinical Pharmacy with research interests in pharmacovigilance, behavioral interventions in mental health, and AI applications in clinical decision support. Experience includes digital health research with Bloomsbury Health (London) and pharmacovigilance practice in patient support programs. Published work covers drug awareness among healthcare providers, postpartum depression management, and patient safety reporting. What was reviewed?
This systematic review and meta-analysis investigated the relationships between biological heavy metal concentrations and breast cancer (BC) risk, focusing on the implications for heavy metal certification programs such as the Heavy Metal Tested and Certified (HTMC) initiative. The review synthesized data from 36 epidemiological studies across five continents, comprising 4,151 individuals, to analyze differences in nine heavy metals categorized as essential, probably essential, or potentially toxic in various human biological specimens (plasma/serum, tissue, hair, and toenails). The central aim was to clarify which heavy metals and biological matrices are associated with BC risk, critically evaluate the underlying mechanisms, and highlight current knowledge gaps relevant to public health and regulatory frameworks.
Who was reviewed?
The review encompassed studies involving human participants drawn from general populations worldwide, with no restrictions on ethnicity or geography. The included studies compared individuals diagnosed with breast cancer (cases) to those without the disease (controls), assessing long-term exposure to heavy metals as indicated by their concentrations in plasma/serum, tissue, hair, or toenails. The dataset represented a diverse global cohort, including populations from Asia, Europe, Africa, South America, and North America. All studies included in the meta-analysis were case–control in design, met minimum quality criteria (no low-quality studies included), and reported direct measurements of heavy metal content in biological samples collected from both BC patients and healthy controls.
Most important findings
| Heavy Metal | Association with Breast Cancer | Relevant Specimen(s) | Regional Differences/Notes |
|---|---|---|---|
| Copper (Cu) | Higher in BC patients vs controls | Plasma/serum, tissue | Significant in Asia, not Europe |
| Zinc (Zn) | Lower in BC patients (plasma/serum, hair); higher in tissue | Plasma/serum, hair, tissue | Significant in Africa and Asia; not Europe/S. America |
| Manganese (Mn) | Lower in BC patients | Plasma/serum | Limited studies, findings are less robust |
| Cadmium (Cd) | Higher in BC patients | Plasma/serum, hair | Significant in Asia (serum), Europe (hair) |
| Lead (Pb) | Higher in BC patients (all specimens); lower in hair | Plasma/serum, hair | Limited studies; findings are less robust |
| Chromium (Cr) | No consistent significant difference | Plasma/serum, hair, toenails | One positive finding in Asian hair |
| Cobalt (Co) | No consistent significant difference | Plasma/serum, hair | One positive finding in hair |
| Iron (Fe) | No consistent significant difference except higher in BC tissue | Tissue, plasma/serum, hair, toenails | Limited studies in tissue |
| Nickel (Ni) | No consistent significant difference | Plasma/serum, hair | No robust association |
Key implications
The findings indicate that higher levels of copper and cadmium, and lower levels of zinc and manganese in plasma/serum, are associated with breast cancer risk, highlighting the need for precise heavy metal certification standards. For the HTMC program, specimen selection and regional dietary exposures must be considered, as must the mechanistic links between metal imbalance and disease, to better inform regulatory thresholds and screening protocols. Larger, standardized studies are required to establish robust, causally informative exposure biomarkers.
Citation
Liu L, Chen J, Liu C, Luo Y, Chen J, Fu Y, Xu Y, Wu H, Li X, Wang H. Relationships Between Biological Heavy Metals and Breast Cancer: A Systematic Review and Meta-Analysis. Front Nutr. 2022;9:838762. doi:10.3389/fnut.2022.838762
Heavy metals are high-density elements that accumulate in the body and environment, disrupting biological processes. Lead, cadmium, arsenic, mercury, nickel, tin, aluminum, and chromium are of greatest concern due to persistence, bioaccumulation, and health risks, making them central to the HMTC program’s safety standards.
Cadmium is a persistent heavy metal that accumulates in kidneys and bones. Dietary sources include cereals, cocoa, shellfish and vegetables, while smokers and industrial workers receive higher exposures. Studies link cadmium to kidney dysfunction, bone fractures and cancer.
