While copper is a vital nutrient required for normal iron metabolism and blood cell formation, high levels of copper in the blood have been linked to increased risk of breast cancer. In fact, tissue concentrations of copper can be greatly elevated in breast cancer. Copper has been shown to promote angiogenesis in existing cancers and appears to have a role in breast cancer cell migration and invasion.
Inducing copper deficiency have been shown to reduce tumor growth and angiogenesis in mouse models of HER2 overexpressing (HER2+), triple negative (ER-/PR-/HER2-) and inflammatory breast cancer (IBC). In addition, reducing copper levels in breast cancer patients at high risk for recurrence has been reported to promote tumor dormancy and help prevent relapse. Now a new study has described how copper chelation (i.e., using a drug to remove copper from the body) reduces metastasis of highly aggressive triple negative breast cancer cells.
Food sources of copper
The following foods have especially high concentrations of copper:
Calf's liver contains 12 to 15 mg of copper per 100 g (3.5 oz.), which is well above the recommended dietary allowance (RDA) of 0.9 mg per day. On the other hand, the copper content of chicken liver is about 0.5 mg per 100 g. The foods below contain far less copper than calf's liver, but are potentially significant sources if consumed frequently:
- Basil pesto
- Chocolate & cocoa powder
- Lima beans
- Nuts, including almonds, Brazil nuts, cashews, hazelnuts, peanuts, pecans, pine nuts, pistachio nuts, walnuts
- Pumpkin seeds
- Sesame seeds
- Shellfish, especially oysters, squid (calamari) & lobster
- Defatted soy flour products, e.g., soy protein isolate, textured soy protein
- Sun-dried tomatoes
- Sunflower seeds
Most nuts are a significant source of copper. However, walnuts have significant chemopreventive properties and should be consumed in moderation rather than avoided because of their copper content. The copper contained in most common foods can be found at SELFNutritionData. Note that curcumin, the most biologically active ingredient in turmeric, has been shown to act as a copper chelator.
Unless you are anemic, the U.S. Recommended Dietary Allowance (RDA) for copper of approximately 0.9 mg per day for adults can be used as a guide. It makes sense not to exceed this intake, on average, but not to fall far below it either.
Other sources of copper exposure
Despite the fact that U.S. residents typically consume more than enough copper and copper deficiency is rare, most multivitamins contain copper. Copper cookware and copper jewelry (including red, rose or pink gold) are other potential sources of copper exposure. It has been demonstrated that copper bracelets can deliver copper through the skin. Soldering copper or copper alloys or otherwise working with copper can also result in exposure. In addition, living near copper mining or smelting operations can result in inhalation of airborne dust incorporating copper.
Latest research describes effects of reducing copper on TN BC
The study referenced above was designed to investigate the mechanism of action by which copper depletion reduces metastasis of triple negative breast cancer. Copper provides necessary metallic ions for a number enzymes involved in malignant progression. The copper chelator tetrathiomolybdate has been reported to increase survival in high-risk triple negative patients. However, a lack of clear understanding as to how copper depletion reduces metastasis has been an obstacle to advancing to phase II trials of tetrathiomolybdate. The current study was intended to address this shortcoming.
Since, according to the authors, tetrathiomolybdate appears to hinder metastasis more than primary tumor growth, they first identified a subpopulation of highly metastatic SOX2/OCT4+ cells within primary triple negative tumors and focused their attention on these cells. The authors then discovered and described a metabolic defect shared by the cells, as well as a relevant downstream pathway associated with metastatic progression.
The highly metastatic cells were found to incorporate high copper levels and were demonstrated to be very sensitive to tetrathiomolybdate, including loss of invasion. Copper depletion was also demonstrated to disrupt mitochondrial respiration in the cells. Overall, the study findings serve to identify and describe what the authors refer to as a "copper-metabolism-metastasis axis" which should be helpful in developing next-generation therapeutic trials.
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Selected breast cancer studies
Connecting copper and cancer: from transition metal signalling to metalloplasia
Ge EJ, Bush AI, Casini A, Cobine PA, Cross JR, DeNicola GM, et al. Connecting copper and cancer: from transition metal signalling to metalloplasia. Nature Reviews Cancer. Springer Science and Business Media LLC; 2021; 10.1038/s41568-021-00417-2
Copper in tumors and the use of copper-based compounds in cancer treatment
da Silva DA, De Luca A, Squitti R, Rongioletti M, Rossi L, Machado CM, et al. Copper in tumors and the use of copper-based compounds in cancer treatment. Journal of Inorganic Biochemistry. Elsevier BV; 2021;:111634 10.1016/j.jinorgbio.2021.111634
Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer
Liu YL, Bager CL, Willumsen N, Ramchandani D, Kornhauser N, Ling L, et al. Tetrathiomolybdate (TM)-associated copper depletion influences collagen remodeling and immune response in the pre-metastatic niche of breast cancer. npj Breast Cancer. Springer Science and Business Media LLC; 2021; 7 10.1038/s41523-021-00313-w
Potential Diagnostic Significance of Salivary Copper Determination in Breast Cancer Patients: A Pilot Study
Bel’skaya LV, Sarf EA, Shalygin SP, Postnova TV, Kosenok VK. Potential Diagnostic Significance of Salivary Copper Determination in Breast Cancer Patients: A Pilot Study. Biological Trace Element Research. Springer Science and Business Media LLC; 2021; 10.1007/s12011-021-02710-5
Zn, Cu, and Fe Concentrations in Dehydrated Herbs (Thyme, Rosemary, Cloves, Oregano, and Basil) and the Correlation with the Microbial Counts of Listeria monocytogenes and Other Foodborne Pathogens
García-Galdeano JM, Villalón-Mir M, Medina-Martínez J, Vázquez-Foronda LM, Zamora-Bustillos JG, Agil A, et al. Zn, Cu, and Fe Concentrations in Dehydrated Herbs (Thyme, Rosemary, Cloves, Oregano, and Basil) and the Correlation with the Microbial Counts of Listeria monocytogenes and Other Foodborne Pathogens. Foods. MDPI AG; 2020; 9:1658 10.3390/foods9111658
Mitochondrial copper depletion suppresses triple-negative breast cancer in mice
Cui L, Gouw AM, LaGory EL, Guo S, Attarwala N, Tang Y, et al. Mitochondrial copper depletion suppresses triple-negative breast cancer in mice. Nature Biotechnology. Springer Science and Business Media LLC; 2020; 10.1038/s41587-020-0707-9
Intratumoral Copper Modulates PD-L1 Expression and Influences Tumor Immune Evasion
Voli F, Valli E, Lerra L, Kimpton K, Saletta F, Giorgi FM, et al. Intratumoral Copper Modulates PD-L1 Expression and Influences Tumor Immune Evasion. Cancer Research. American Association for Cancer Research (AACR); 2020; 80:4129-4144 10.1158/0008-5472.can-20-0471
Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation
Wang J, Luo C, Shan C, You Q, Lu J, Elf S, et al. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation. Nature Chemistry. Springer Science and Business Media LLC; 2015; 7:968-979 10.1038/nchem.2381
Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse
Jain S, Cohen J, Ward M, Kornhauser N, Chuang E, Cigler T, et al. Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse. Annals of Oncology. Elsevier BV; 2013; 24:1491-1498 10.1093/annonc/mds654
Effect of Cu supplementation on genomic instability in chemically-induced mammary carcinogenesis in the rat
Bobrowska B, Skrajnowska D, Tokarz A. Effect of Cu supplementation on genomic instability in chemically-induced mammary carcinogenesis in the rat. Journal of Biomedical Science. Springer Science and Business Media LLC; 2011; 18:95 10.1186/1423-0127-18-95
Dietary Supplements and Mortality Rate in Older Women
Mursu J. Dietary Supplements and Mortality Rate in Older Women. Archives of Internal Medicine. American Medical Association (AMA); 2011; 171:1625 10.1001/archinternmed.2011.445