![]() The importance of iodine in breast cancer is further emphasized by the adjuvant effects of iodine (I 2) supplementation in combination with doxorubixin for breast cancer treatment 23. Iodine deficiency, therefore, may contribute to breast cancer and its progression directly within breast tissue, and secondarily by decreased thyroid function leading to metastasis. Since iodine deficiency is a major cause of hypothyroidism, breast cancer with distant metastasis may be promoted in part by reduced thyroid function, where slower tumor growth (precluding earlier diagnosis), yet increased invasiveness could be consequential. These findings provide a potential explanation for increased distant breast tumors at time of diagnosis. Studies implanting human breast cancer as well as hepatocellular carcinoma cells in nude mice demonstrate that hypothyroidism reduces tumor growth, but at the same time enhances invasiveness and metastasis 22. In contrast, one study suggested hypothyroidism actually reduces the risk of breast cancer 21, however, this study was done in older, mostly postmenopausal women and thus, this conclusion may not be relevant to the population of younger women (age 25-39) at risk for increased invasive breast cancer discussed here. Iodine deficiency is an important cause of thyroid deficiency the potential linkage between thyroid disease and breast cancer has been a matter of considerable interest 7, 14 - 16 and has been extensively reviewed 17 - 20. The mechanism of action of iodine's anticancer effect may be complex, and roles as an antioxidant, promoting differentiation and apoptosis related to breast cancer have been proposed 13. In animal models of breast cancer, iodine in supplement or seaweed form, has demonstrated beneficial effects in suppressing breast cancer cell and tumor growth 12. Iodine is taken up by the sodium/iodide symporter in the breast and its role is important in promoting the development of normal versus neoplastic breast tissue development 12. Furthermore, emigration of Japanese women 10 and adopting a western diet 11 is associated with higher breast cancer rates. Dietary iodine has also been previously proposed to play a protective role in breast cancer 8, to a large degree based on the increased iodine consumption of dietary iodine in Japanese women, having and exceptionally low incidence of breast cancer 9. ![]() The hypothesis that iodine deficiency in the United States, plays a role in the increased incidence of breast cancer with distant involvement, is discussed here in the context of these three factors.ฤก) Pathogenesis: Iodine deficiency has been proposed to play a causative role in the development of breast cancer 6, 7. In response, the original authors 5 suggested causal association need explain: 1) why a proposed agent or risk factor would cause advanced disease, 2) why it would preferentially affect the youngest women, and 3) how temporal trends in the proposed causative agent have changed since the mid-1970s 5. There have been explanations proposed in several letters, including vaccination 2, advanced-age at first pregnancy 3 as well as folate supplementation 4, however these explanations have not been particularly satisfying. Understanding the causes for these changes in cancer demographics is particularly important in view of the young age of these women, as well as the poor survival rate for women with distant metastatic breast disease. 1 This disturbing trend was also observed in women age 40-54, albeit to a letter extent. ![]() The incidence of breast cancer with distant involvement at diagnosis is increasing in young women, age 25-39, possibly at an accelerating rate, as previously demonstrated by Johnson et al.
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