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.

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.

Inclusion Criteria:

- Sub-group I - BRCA1 mutation carriers

1. Carrier-status of BRCA1 mutation
2. Age >20 years
3. Have a breast magnetic resonance imaging and/or ultrasonography and/or mammography that reveals no disease at maximum 9 months after enrollment
4. Be able to give information consent and sign an informed consent form
5. Be willing to comply with all of the study procedures as per the protocol
6. Be willing to inform researchers about current or any new pregnancy
7. Sub-optimal Se level in the blood

Sub-group II - Females from families with hereditary breast cancers but without BRCA1 mutations

1. Age ≥40 years
2. Age ≥20 years for women that have been diagnosed previously with breast cancer
3. Positive medical history of family, matching criteria of hereditary breast/ovarian cancer (HBO) (Appendix 1)
4. No personal history of cancer except for breast cancer and non-melanoma skin cancers
5. Have a breast magnetic resonance imaging/ultrasonography/mammography that reveals no disease at maximum 9 months after enrollment
6. Be able to give information consent and sign an informed consent form
7. Absence of BRCA1 mutations after testing for at least three founder mutations (BRCA1 5382insC, BRCA1 300T/G, BRCA1 4154delA)
8. Be willing to comply with all of the study procedures as per the protocol
9. Be willing to inform researchers about current or any new pregnancy
10. Sub-optimal Se level in the blood

Exclusion Criteria:

Sub-group I - BRCA1 mutation carriers

1. Diagnosis of any previous cancer except for breast cancers and non-melanoma skin cancers
2. Absence of a magnetic resonance imaging/ultrasonography/mammography that reveals no disease at maximum 9 months after enrollment
3. Current pregnancy or breast-feeding
4. Optimal Se level in the blood
5. Age <20 years
6. Any medical illness, which, in the investigator's opinion, cannot be adequately controlled with appropriate therapy
7. 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

1. Diagnosis of any previous cancer except for breast cancers and non-melanoma skin cancers
2. Absence of magnetic resonance imaging and/or ultrasonography and/or mammography that reveals no disease at maximum 9 months after enrollment
3. Absence of matching pedigree/clinical/molecular criteria of HBO (Appendix 1)
4. Presence of BRCA1 mutation
5. Current pregnancy or breast-feeding
6. Optimal Se level in the blood
7. Age <40 years except for women that have been previously diagnosed with breast cancer
8. Any medical illness, which, in the investigator's opinion, cannot be adequately controlled with appropriate therapy
9. 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)

We still did not collect all the required participants. It is hard to tell that the data could be useful later on.

The selected randomization method is block randomization with randomly chosen blocks sizes.

Randomization must take place before 120 days after the Screening Visit (Day 0). After confirmation that the patient meets all eligibility criteria for the study, the patient will be randomly assigned (1:1) to either placebo or supplementation group. Patients with selenium deficiency can choose between diet modification and supplementation group.

The last step of randomisation is the blinding/assigning procedure - connecting randomization numbers with placebo or supplement packages numbers and assigning them to the subjects. All SELINA personnel, participants and clinicians will be blinded to the treatment allocation; only the Statistical Center will have the possibility to unblind the data.