The relationship between iron and breast cancer is multifaceted and not fully understood. Iron is an essential nutrient and its concentration in cells is regulated very closely. However, tumors are iron consumers. Breast cancer cells have abnormal pathways of iron acquisition, storage and regulation, suggesting that reprogramming of iron metabolism is an important aspect of cancer cell survival. Iron facilitates cell proliferation and growth. It is also an important contributor to tumor angiogenesis (the growth of new blood vessels). It is possible that iron has a more important role in the growth and metastasis of breast cancer than in its initial development. Now a new study has reported that the addition of iron in breast cancer cells and their microenvironment protects them from being killed by natural killer cells.

While several studies have reported a link between high iron levels and increased breast cancer risk, iron deficiency also appears to promote breast cancer in some circumstances. Based on the available evidence to date, adequate but not high or dangerously low levels of iron appear to be best. Note that many women undergoing chemotherapy develop anemia, which can result in severe complications and interfere with the ability to complete treatment in a timely manner. Women undergoing breast cancer treatment should follow the recommendations of their oncology teams with respect to the prevention and treatment of anemia.

Sources of iron

Red meat, especially liver, is an abundant dietary source of iron. Several studies have reported that high intake of animal-derived iron (heme iron) is associated with increased risk of breast cancer. One study reported that saturated fat derived from animal sources appears to augment this effect. Another study reported that high red meat consumption during adolescence was associated with increased risk of premenopausal breast cancer. Iron supplements and multivitamins containing iron have also been found to be associated with increased breast cancer risk, especially among postmenopausal and older women. White flour, which in the U.S. is fortified with iron, is another source of iron supplementation. The body absorbs heme iron more effectively than nonheme iron from plant sources such as spinach and dry beans. Assuming adequate iron levels, it may make sense to limit exposure to supplemental iron, as well as sources of heme iron such as red meat, shellfish or any type of liver.

Latest research finds iron protects breast cancer cells from natural killer cells

The study referenced at the beginning of this news story was designed to investigate the role of iron in the anticancer immune function of natural killer cells. To conduct the study, the authors examined the effects of various levels of iron on the activities of natural killer cells (using the natural killer cell line NK-92MI) in ER+/PR+ (MCF-7) and triple negative (MDA-MB-231) breast cancer cells. They measured the cytolysis (a type of cell death) caused by the natural killer cells, in addition to the production of nitric oxide (NO) and tumor necrosis factor alpha (TNFα), as well as ferritin heavy chain (FTH1) gene expression.

Natural killer cells were found to increase the synthesis and release of NO and TNFα into the cell culture medium when co-cultured with both types of breast cancer cells. Addition of iron was found to inhibit the cytolysis of the breast cancer cells; iron reversed the cytotoxicity induced by NO. On the other hand, the iron chelator deferoxamine (DFOM) was shown to increase killer cell cytolysis. The authors conclude that increased iron in breast cancer cells and their microenvironment protects them from natural killer cell cytolysis.