Iodine Supplementation on Breast Cancer

Hospital General Regional #1 IMSS, Queretaro México, Clínica Hospital Dr. Ismael Vázquez Ortiz ISSSTE, Queretaro Mexico, Hospital Medico TEC100, Queretaro México

The trial investigates the effect of oral supplement of molecular iodine (I2) alone and in combination with 4 to 6 cycles of FEC/TE (5-fluorouracil, epirubicin, cyclophosphamide/taxotere, epirubicin) treatment in woman diagnosticated with early (stage II) and advance (stage III) breast cancer, respectively. The study analyzes the clinical response [tumor size, thyroid status, side effects (Common Toxicity Criteria V4.0)] and molecular mechanisms in the tumor samples (transcriptomic, proteins and immune responses).

The leading causes of failure of breast cancer treatment are the rapid development of metastases and tumor resistance to antineoplastic drugs. Anthracyclines (doxorubicin (DOX), epirubicin, etc.) are the golden standard in neoadjuvant therapy and are commonly used in the FEC/TE (5-fluorouracil, epirubicin, cyclophosphamide/taxotere, epirubicin) combination therapy during advanced breast cancer. However, even when treated with this potent chemotherapeutic combination, 30% of patients develop chemoresistance and cardiomyopathic side effects. Previous studies support that the oral supplement of molecular iodine (I2) exerts synergistic antineoplastic and cardioprotective impact when used in combination with the DOX in rodent and canine mammary cancer model. The present study performed two randomized clinical groups including women with early (stage II) and advanced (stage III) breast cancer. In the Early group, women were treated with I2 (5 mg/day) or placebo (colored water) for 7 to 35 days. In the Advanced group, patients received treatment (I2 or placebo) along with 4 to 6 cycles of FEC/TE treatment. The study analyzes the clinical response [tumor size, thyroid status, side effects (Common Toxicity Criteria V4.0)] and molecular mechanisms in the tumor samples (transcriptomic, proteins and immune responses).

two randomized clinical groups including women with early (stage II) and advanced (stage III) breast cancer. In the Early group, women were treated with I2 (5 mg/day) or placebo (colored water) for 7 to 35 days. In the Advanced group, patients received treatment (I2 or placebo) along with 4 to 6 cycles of FEC/TE treatment.

The daily supplement of a vegetable colored water solution (drops) for 7 to 35 days in early breast cancer diagnosticated woman. Placebo: vegetable colored water solution (drops). Evaluate the activity of placebo on tumor size, and molecular tumor response, as well as side effects attenuation

The daily supplement of an iodine solution (drops, 5 mg/day) for 7 to 35 days in early breast cancer diagnosticated woman

The daily supplement of an vegetable colored water solution (drops) within 4 to 6 cycles of chemotherapy with FEC/TE in advanced breast cancer diagnosticated woman. Placebo: vegetable colored water solution (drops). Evaluate the adjuvancy of placebo in FEC/TE treatment on tumor size and molecular tumor response, as well as side effects attenuation.

The daily supplement of an iodine solution (drops, 5 mg/day) within 4 to 6 cycles of chemotherapy with FEC/TE in advanced breast cancer diagnosticated woman Drug: Iodine solution (5 mg/day). Evaluate the adjuvancy of I2 on FEC/TE treatment on tumor size and molecular tumor response, as well as side effects attenuation. Other Name: evaluating the adjuvancy of iodine supplement in FEC/TE treatment

Selected patients with early breast cancer (stage II) non-pretreated received colored water solution (placebo) within the time before the hospital assigned them to her surgery (7 to 35 days).

Selected patients with early breast cancer (stage II) non-pretreated received iodine solution (Experimental) within the time before the hospital assigned them to her surgery (7 to 35 days).

The selected patients with advanced breast cancer (stage III) non-pretreated received colored water solution (placebo) within the time of oncology designed chemotherapy treatment FEC/TE (4 or 6 cycles/ every 21 days).

The selected patients with advanced breast cancer (stage III) non-pretreated received iodine solution (experimental) within the time of oncology designed chemotherapy treatment (4 or 6 cycles/ every 21 days).

The size of the tumor is calculated by measuring the largest diameter of the tumor in the axial plane. The first measurement is obtained in the mammography taken before the start of the protocol and the second measurement is made on the tissue after surgery. The change percentage is obtained by dividing the final size between the initial size by 100.

Presence or not of: Edema, hand-foot syndrome, anorexia, vomiting, diarrhea, nausea, asthenia (patient interview and clinical auscultation)

Differential blood count gives relative percentage of each type of white blood cell and helps reveal abnormal white blood cell populations (eg, blasts, immature granulocytes, or circulating mature cells in the peripheral blood).

Serum quantification of thyroxine, triiodothyronine, and thyroid stimulating hormone (nmol/ml) by ELISA Method

Measurement of creatine kinase myocardial band (CK-MB) concentration in serum (ImU/ml) by Colorimetric Method.

Estrogen receptor (ER), Progesterone receptor (PR) and Human epidermal growth factor receptor 2 (HER2) presence in biopsy (initial) and tumor sample after treatments (final) by immunohistochemical method (number of positive cells/field).

The follow-up of the disease-free survival (DFS) at 5 years. (patient interview and clinical auscultation each six months)

Inclusion Criteria: Histologically confirmed, stage II or III breast cancer Scheduled to surgical of the primary tumor (stage II) Will receive neoadjuvant FEC/TE chemotherapy (stage III). age > 18 and < 81 years Non-pregnant Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: Known sensitivity to iodine or FEC/TE Concurrent severe and/or uncontrolled disease Myocardial infarction within the last six months before the study Unstable or uncontrolled hypertension Thyroid dysfunction

De-identified individual participant data for all primarily and secondary outcome measures will be made available

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Garcia-Solis P, Alfaro Y, Anguiano B, Delgado G, Guzman RC, Nandi S, Diaz-Munoz M, Vazquez-Martinez O, Aceves C. Inhibition of N-methyl-N-nitrosourea-induced mammary carcinogenesis by molecular iodine (I2) but not by iodide (I-) treatment Evidence that I2 prevents cancer promotion. Mol Cell Endocrinol. 2005 May 31;236(1-2):49-57. doi: 10.1016/j.mce.2005.03.001. Epub 2005 Apr 13.