Abstract 3509: Iodine exhibits dual effects on breast cancer as a co-treatment with anthracyclines: Antineoplastic synergy and cardioprotector

Breast cancer (BC) is the most common type of cancer worldwide in reproductive-age women. Genetic (mutations in the gene BRCA), reproductive (menarche, pregnancy, and menopause), and environmental factors (lipids, alcohol, iodine, etc.) are known to be involved in BC etiology. Previous studies have demonstrated that molecular iodine (I2) has an antineoplastic effect on mammary cancer cells in vivo as well as in vitro through activation of caspase-dependant apoptotic pathways. It has also been demonstrated that this element has a powerful antioxidant effect, even greater than that of vitamin E. These dual beneficial effects of I2 were corroborated in rats with methyl-nitrosourea-induced mammary cancers treated with anthracyclines (AC) – an antineoplastic drug that also has a free radical cardiopathic secondary effect but is commonly used in humans. In combination with AC, I2 acted as an adjuvant, decreasing tumoral size and providing significant cardioprotection. In the present study we did a clinical evaluation of the additive effect of I2 (5 mg/day) or placebo (vegetable dye) with a common antineoplastic cocktail containing AC (Fluorouracil, Epirubicyn, Cyclophosphamide, Taxotere [FEC/TE], four to six cycles) in advanced BC patients (stages III and IV). Preliminary results (N=14) show a significant antineoplastic adjuvant effect of I2 when administered together with FEC/TE, and complete remission in 33 % of the cases. This result permitted conservative surgery on 3 of the 14 patients. Molecular analysis showed that in the tumoral mass of I2-supplemented patients, there was a significant decrease of the cell proliferation rate, as tested with Proliferating Cell Nuclear Antigen, PCNA immunohistochemistry (98.6% vs 80.8%), and of cyclin D1 expression (1.2 ±0.6 vs 0.3 ± 0.06; real time PCR) when compared with the control group (FEC/TE+ placebo). We also found a significant increase in the apoptosis rate (Terminal deoxynucleotidyl transferase dUTP nick end labeling; TUNEL) in the FEC/TE + I2 group (42.2 ± 4.8 vs 73.2 ± 1.8) Significantly lower serum levels of the cardiac kinase CK-MB were found in FEC/TE +I2 patients (21.5 ± 3.8 vs 8.0 ± 2.6 UI/ml) indicating a protective effect against myocardial damage. We confirmed the iodine intake of our patients by measuring the levels of this molecule in urine samples (44 ± 4.5 vs 256 ± 13 ug/dl). In conclusion, our results show a significant dual effect of iodine with FEC/TE that lead us to propose its implementation as a novel treatment for BC that could, in the future, allow lower doses of standard chemotherapy, reducing adverse effects and cost. Acknowledgements to Biol. Felipe Ortiz and Biol. Paloma Olvera for the technical support, and Dr. Dorothy Pless for proofreading. Study partially supported by UNAM/DGAPA IN201210 and CONACYT 78955 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3509. doi:10.1158/1538-7445.AM2011-3509