Preoperative Use of Tocotrienol From Annatto Bixa Orellana L. in Breast Cancer Patients: a Prospective Clinical Trial.

Study Overview
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Brief Summary
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Tocotrienols have shown strong in vitro and in vivo anti-oxidant and anticancer activity, promoting apoptosis and regulating oncogenic targets in breast cancer. However their clinical use is still experimental especially in preoperative setting, where there are still no data of antioxidant and antiinflammatory beneficial roles. This study is a prospective observational clinical study enrolling 50 patients with primary breast cancer (T1-2, N0-1, M0) who received 4-weeks oral treatment of delta-T3 before surgery (200 mg/twice daily) with personalized nutritional and psychoeducational support. This study evaluates the effects of treatment on oxidant (tock fast-Li Starfish) and antioxidant capacity (TAC Track, Li Starfish), anti-inflammatory activity (complete profiling of adaptive and innate cell immunity, immunologic serum markers (miRNA)), immunological response on tumor (gene expression profiling on preoperative tissue tumor biopsy and on surgical specimen), TNF-alpha, IL-6 and VEGF and proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines. This study evaluates the effects of treatment on oxidant (tock fast-Li Starfish) and antioxidant capacity (TAC Track, Li Starfish), on anti-inflammatory activity (complete profiling of adaptive and innate cell immunity, immunologic serum markers (miRNA)), on immunological response on tumor (gene expression profiling on preoperative tissue tumor biopsy and on surgical specimen), on TNF-alpha, IL-6 and VEGF, on proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines.

Detailed Description
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An open-label, single center, phase 2 prospective observational clinical study

Official Title
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Preoperative Use of Tocotrienol Associated With Personalized Nutritional and Psychoeducational Support in Women With Primary Breast Cancer.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Tocotrienol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically confirmed operable primary breast cancer (T1-T2 N0-1 M0) absence of distant metastasis signed informed consent. Exclusion Criteria: Previous malignancies other than in situ cervical carcinoma or nonmelanoma skin cancer Breast cancer recurrence Metastatic breast cancer Non-epithelial breast cancer at histological examination In situ lobular breast cancer Participation in other randomized clinical trials that could interfere with current study Living distant from center and unable to attend for check-ups and meetings

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tocotrienol<br>Subjects receiveTocotrienol 200 mg/twice daily before surgery | Drug: Tocotrienol<br>* Tocotrienol 200 mg orally twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in blood oxidant capacity | Oxidant capacity (through tock fast-Li Starfish) (µmol/L) was measured in patients' serum samples. | 4 weeks | 
| Changes in blood antioxidant capacity | Antioxidant capacity (through TAC Track, Li Starfish) (µmol/L) was measured in patients' serum samples. | 4 weeks | 
| Absolute and relative changes in peripheral blood mononuclear cells obtained before and after four weeks of tocotrienol treatment, as detected by 13-colors citofluorimetry analysis | Peripheral blood mononuclear cells were measured by 13-color cytofluorimetry analysis in patients' serum samples. | 4 weeks | 
| Changes of immune-related miRNA levels in patients' serum samples obtained before and after four weeks of tocotrienol treatment, as determined by quantitative real-time PCR analysis | Immune-related miRNA levels were determined by quantitative real-time PCR analysis in patients' serum samples obtained before and after four weeks of tocotrienol treatment | 4 weeks | 
| Changes in immune response associated gene levels in preoperative tissue tumor biopsies and in surgical specimens, obtained before and after four weeks of tocotrienol treatment, respectively, as determined by gene expression profiling analysis | Immune response associated gene levels were determined by gene expression profiling analysis in preoperative tissue tumor biopsies and in surgical specimens, obtained before and after four weeks of tocotrienol treatment | 4 weeks | 
| Changes in serum inflammatory cytokines and growth factor | Blood inflammatory cytokines and growth factor (through TNF-alpha (pg/ml), IL-6 (pg/ml) and VEGF (pg/ml) quantifications) were measured in patients' serum samples | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-induced changes in proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines | Treatment-induced changes in proliferation/apoptosis, anti-inflammatory and anti-oxidant activity of breast cancer cell lines was measured through cell culture analysis. | 12,24 and 72 hours | 
| Changes in expression of tumor proliferation, hormone receptors and HER2 | Expression of tumor proliferation index (Ki67), estrogen and/progesterone receptor and HER2 oncoprotein by IHC was determined in preoperative tumor biopsies and in surgical specimens | 4 weeks |