Prevention of Female Cancers by Optimization of Selenium Levels in the Organism.

Study Overview
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Brief Summary
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Hypothesis to be tested: Oral supplementation or diet modifications of selenium to a specified range will be effective in reducing the risk of developing cancer of any type in women with high risk of breast cancer, as compared to placebo.

Detailed Description
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Primary Objective • To determine the efficacy of oral daily supplementation or diet modification of selenium to an optimal level compared to placebo, in reducing the incidence of any cancers in an at risk population of women over the 60 months of the study. Secondary Objectives To determine the efficacy of oral daily supplementation or diet modification of selenium to an optimal level compared to placebo, in reducing the incidence of breast cancer in an at risk population of women over the 60 months of the study. To explore the relationship between the effects of study supplement or diet modifications on cancer risk and genetic factors. The study will have 7000 participants. All the measurements will be performed via blood tests.

Official Title
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Prevention of Females Malignancies in Families With Hereditary Breast Cancer by Personalized Optimization of Se Levels in the Organism.

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Dietary Supplement: Selenium supplementation or placebo treatment
* Other: Diet modification
* Other: Selenium supplementation or placebo treatment and diet modification


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Sub-group I - BRCA1 mutation carriers Carrier-status of BRCA1 mutation Age >20 years Have a breast magnetic resonance imaging and/or ultrasonography and/or mammography that reveals no disease at maximum 9 months after enrollment Be able to give information consent and sign an informed consent form Be willing to comply with all of the study procedures as per the protocol Be willing to inform researchers about current or any new pregnancy Sub-optimal Se level in the blood Sub-group II - Females from families with hereditary breast cancers but without BRCA1 mutations Age ≥40 years Age ≥20 years for women that have been diagnosed previously with breast cancer Positive medical history of family, matching criteria of hereditary breast/ovarian cancer (HBO) (Appendix 1) No personal history of cancer except for breast cancer and non-melanoma skin cancers Have a breast magnetic resonance imaging/ultrasonography/mammography that reveals no disease at maximum 9 months after enrollment Be able to give information consent and sign an informed consent form Absence of BRCA1 mutations after testing for at least three founder mutations (BRCA1 5382insC, BRCA1 300T/G, BRCA1 4154delA) Be willing to comply with all of the study procedures as per the protocol Be willing to inform researchers about current or any new pregnancy Sub-optimal Se level in the blood Exclusion Criteria: Sub-group I - BRCA1 mutation carriers Diagnosis of any previous cancer except for breast cancers and non-melanoma skin cancers Absence of a magnetic resonance imaging/ultrasonography/mammography that reveals no disease at maximum 9 months after enrollment Current pregnancy or breast-feeding Optimal Se level in the blood Age <20 years Any medical illness, which, in the investigator's opinion, cannot be adequately controlled with appropriate therapy Participation in any other clinical study involving a medical, surgical, nutritional, or life-style intervention (unless individuals are no longer receiving any intervention and they are in the follow-up phase only) Sub-group II - Females from families with hereditary breast cancers but without BRCA1 mutations Diagnosis of any previous cancer except for breast cancers and non-melanoma skin cancers Absence of magnetic resonance imaging and/or ultrasonography and/or mammography that reveals no disease at maximum 9 months after enrollment Absence of matching pedigree/clinical/molecular criteria of HBO (Appendix 1) Presence of BRCA1 mutation Current pregnancy or breast-feeding Optimal Se level in the blood Age <40 years except for women that have been previously diagnosed with breast cancer Any medical illness, which, in the investigator's opinion, cannot be adequately controlled with appropriate therapy Participation in any other clinical study involving a medical, surgical, nutritional, or life-style intervention (unless individuals are no longer receiving any intervention and they are in the follow-up phase only)

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Supplementation of selenium or diet modification will be effective in reducing the risk of developing breast cancer in women with high risk, as compared to placebo. The null hypothesis assumes no significant differences between the supplementation and placebo groups. The alternative hypothesis assumes that patients with high risk of breast cancer in supplementation or diet modification group with optimal selenium level will have significantly reduced risk of developing cancer in relation to the placebo group with selenium deficiency. The comparison of disease-free survival time intervals is best covered by Cox Regression and is represented by a Kaplan-Meier survival curve tested by log- rank test. The comparison of proportions of diseased and healthy subjects in the supplementation arm with respect to the placebo arm is best attempted using the Fisher Exact Test. Graphical representation should be based on bar plots for percentages and/or raw numbers, or a similar representation.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BRCA(+) Selenium deficiency<br>Placebo: 100 Supplement: 100 | Dietary Supplement: Selenium supplementation or placebo treatment<br>* Patients from this group will receive selenium supplement to achieve optimal selenium level<br>|
| Active Comparator: BRCA(+) Selenium excess<br>Diet modification: 500 Observation: 500 | Other: Diet modification<br>* Patients from this group will have modified diet over the course of the study. Diet modification is aimed to lower selenium concentration in blood.<br>|
| Active Comparator: BRCA(-) Selenium deficiency<br>Placebo: 900 Supplement: 900 Diet modification: 900 Observation: 900 | Other: Selenium supplementation or placebo treatment and diet modification<br>* In this group patients will receive supplement, placebo or diet modification. The goal is to raise selenium concentration in blood<br>|
| Active Comparator: BRCA(-) Selenium excess<br>Diet modification: 1100 Observation: 1100 | Other: Diet modification<br>* Patients from this group will have modified diet over the course of the study. Diet modification is aimed to lower selenium concentration in blood.<br>|
| Active Comparator: BRCA(+) Selenium excess, age > 50<br>Diet modification: 200 Observation: 200 | Other: Diet modification<br>* Patients from this group will have modified diet over the course of the study. Diet modification is aimed to lower selenium concentration in blood.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of any new cancer | Cancer diagnosis will be determined by routine clinical management and confirmed by central pathology review. Cancer-free survival is defined as the period of time between randomization and diagnosis of cancer, or - for patients who do not develop cancer - the period of time between randomization and last contact or death unrelated to cancer. | within 60 months of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of new breast cancer | Cancer diagnosis will be determined by routine clinical management and confirmed by central pathology review. Cancer-free survival is defined as the period of time between randomization and diagnosis of cancer, or - for patients who do not develop cancer - the period of time between randomization and last contact or death unrelated to cancer. | within 60 months of the study | 
| Proportion of any other cancers (besides breast cancers) at the end of 60 months | Cancer diagnosis will be determined by routine clinical management and confirmed by central pathology review. Cancer-free survival is defined as the period of time between randomization and diagnosis of cancer, or - for patients who do not develop cancer - the period of time between randomization and last contact or death unrelated to cancer. | within 60 months of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Selenium, Supplement, Prevention, Females, Risk