Breast Cancer
Conditions
Brief summary
This is a pilot study evaluating the effect of hydroxytyrosol, a component of olive oil, on mammographic density in women at high risk of developing breast cancer.
Detailed description
This is a pilot study evaluating the effect of hydroxytyrosol, a component of olive oil, on mammographic density in women at high risk of developing breast cancer. Participants will take hydroxytyrosol orally once daily for 1 year. Breast density as determined by mammography and the safety/toxicity of hydroxytyrosol will be assessed.
Interventions
DRUGHydroxytyrosol
Sponsors
The Methodist Hospital Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female aged ≥18 years of age. 2. Elevated risk of breast cancer as defined by at least one of the following categories and have declined tamoxifen and/or raloxifene therapy: 1. Diagnosis of lobular carcinoma in situ (LCIS), atypical ductal, or lobular hyperplasia. 2. A known deleterious mutation in BRCA1, BRCA2, PTEN, or TP53. (Note: The participant must be a documented carrier to meet this criterion. If there is a known mutation in a hereditary breast cancer susceptibility gene in a participant's family member, the participant herself must have undergone genetic testing as per National Comprehensive Cancer Network guidelines to be eligible per this criterion.) 3. Modified Gail/CARE model risk at 5 years ≥ 1.67%. (Note: Risk models are to be used only if there is no known previous diagnosis of resected ductal carcinoma in situ \[DCIS\] or LCIS and there is no known deleterious mutation in BRCA1, BRCA2, PTEN, or TP53) 4. 10% or more probability of BRCA mutation by BRCAPRO or similar model 3. Must have at least one breast available for imaging and biopsy. A previously irradiated breast (i.e., for resected DCIS) is not evaluable for breast imaging or biopsy. a. Allow for submission of core needle breast material for future use. 4. Baseline mammogram performed within 90 days prior to study entry, done on a digital mammography machine, that are reported as normal or benign. 5. Baseline mammographic density \> 10% based upon the classification system (2 = 11-50%, scattered fibroglandular densities; 3 = 51-75%, heterogeneously dense; 4 = \>75%, extremely dense). Women with a baseline mammographic density of ≤ 10% (1 = ≤10%, breasts are almost entirely fat) will not be eligible 6. Eastern Cooperative Oncology Group performance status of 0-1. 7. Prior anticoagulant therapy use is allowed provided therapy is discontinued at least 7 days prior to the breast biopsy in order to reduce the risk of bleeding. For participants who have taken an anticoagulation within the past 7 days, international normalized ratio must be ≤ 1.5 x institutional upper limit of normal and prothrombin time and partial thromboplastin time ≤ ULN prior to the breast biopsy. 8. Must agree to use effective consistent contraception. Hormone-based birth control (pills, patches, or shots) is allowed. Hormone replacement therapy is not allowed for postmenopausal participants. 9. Must not participate in any other clinical trial for the treatment or prevention of cancer unless they are no longer receiving the intervention and are in the follow-up phase only. Participants must also agree not to join such a trial while participating in this study. 10. Provide written informed consent.
Exclusion criteria
1. DCIS or previous invasive ductal carcinoma. 2. Any prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer and in situ cervical cancer. 3. Prior tamoxifen or raloxifene use in the past 1 year. 4. Pregnant or breastfeeding. 5. Bilateral breast implants. Prior breast reduction surgery is allowed. 6. Mammograms that are reported as suspicious.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Maximum Volumetric Breast Density Percentage | Baseline and 12 months | Change in Maximum Volumetric Breast Density Percentage from Baseline at 12 Months. Maximum volumetric breast density (max VBD%) which is calculated by fibroglandular breast volume divided by total breast volume (checked on the higher side, left or right) was used to obtain the study's endpoints. The primary endpoint was the annualized percent decrease in max VBD% between baseline (BL) and end-of-treatment (EOT) with HT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From informed consent up to 12 months | Number of participants with adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Expression of Ki67 in Tumor Tissue | From baseline and at 12 months | To determine the expression of Ki67 in tumor tissue |
| MRI Breast Density | From baseline and at 12 months | To determine breast density as assessed by magnetic resonance imaging |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hydroxytyrosol Hydroxytyrosol 25 mg orally once daily for 1 year.
Hydroxytyrosol | 51 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lost to Follow-up | 4 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Hydroxytyrosol |
|---|---|
| Age, Customized Median Age | 54 years |
| Menopausal Status Post-menopausal | 29 Participants |
| Menopausal Status Pre-menopausal | 22 Participants |
| Race/Ethnicity, Customized African American | 4 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Caucasian | 41 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants |
| Sex: Female, Male Female | 51 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 51 |
| other Total, other adverse events | 2 / 51 |
| serious Total, serious adverse events | 0 / 51 |
Outcome results
Primary
Change in Maximum Volumetric Breast Density Percentage
Change in Maximum Volumetric Breast Density Percentage from Baseline at 12 Months. Maximum volumetric breast density (max VBD%) which is calculated by fibroglandular breast volume divided by total breast volume (checked on the higher side, left or right) was used to obtain the study's endpoints. The primary endpoint was the annualized percent decrease in max VBD% between baseline (BL) and end-of-treatment (EOT) with HT.
Time frame: Baseline and 12 months
Population: There were 26 patients who had both baseline and end of treatment raw images of mammograms available on which quantitative analysis using volpara software was performed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Hydroxytyrosol | Change in Maximum Volumetric Breast Density Percentage | -0.038 Mean decrease in max VBD percentage |
Secondary
Number of Participants With Adverse Events
Number of participants with adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03
Time frame: From informed consent up to 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hydroxytyrosol | Number of Participants With Adverse Events | 2 Participants |
Other Pre-specified
Expression of Ki67 in Tumor Tissue
To determine the expression of Ki67 in tumor tissue
Time frame: From baseline and at 12 months
Other Pre-specified
MRI Breast Density
To determine breast density as assessed by magnetic resonance imaging
Time frame: From baseline and at 12 months