Iodine Supplementation on Breast Cancer

Study Overview
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Brief Summary
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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).

Detailed Description
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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).

Official Title
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Effect of Dietary Iodine Supplementation on the Proliferation of Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Placebo
* Drug: iodine
* Drug: FEC/TE Placebo
* Drug: FEC/TE iodine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 81 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Early Cancer placebo<br>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 | Drug: Placebo<br>* 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).<br>* Other names: control;|
| Experimental: Early Cancer Iodine<br>The daily supplement of an iodine solution (drops, 5 mg/day) for 7 to 35 days in early breast cancer diagnosticated woman | Drug: iodine<br>* 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).<br>* Other names: experimental;|
| Placebo Comparator: Advanced Cancer FEC/TE placebo<br>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. | Drug: FEC/TE Placebo<br>* 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).<br>|
| Experimental: Advanced Cancer FEC/TE + Iodine<br>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 | Drug: FEC/TE iodine<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response [change in size] | 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. | 20 minutes | 
| Incidence of treatment-emergent adverse events [Safety and Tolerability]). | Presence or not of: Edema, hand-foot syndrome, anorexia, vomiting, diarrhea, nausea, asthenia (patient interview and clinical auscultation) | 40 minutes | 
| Differential Blood Count | 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). | 10 minutes (duration of blood withdrawal)] | 
| Thyroid Test | Serum quantification of thyroxine, triiodothyronine, and thyroid stimulating hormone (nmol/ml) by ELISA Method | 10 minutes (duration of blood withdrawal) | 
| Cardiac damage | Measurement of creatine kinase myocardial band (CK-MB) concentration in serum (ImU/ml) by Colorimetric Method. | 10 minutes (duration of blood withdrawal) | 
| Iodine consumes | Measurement of iodine concentration in urine (ug/mL) by Ion Chromatography Method. | 10 minutes (duration of urine recollection) | 
| Tumor classification type and modification after treatment | 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). | 40 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | The follow-up of the disease-free survival (DFS) at 5 years. (patient interview and clinical auscultation each six months) | Every 6 months for 5 years |