Breast Cancer
Conditions
Keywords
breast atypia, double-blind randomized clinical trial, RCT, celecoxib, COX-2 inhibitor, placebo, high risk for breast cancer, breast epithelial hyperplasia, ki-67, chemoprevention
Brief summary
To assess the effects of twelve months of celecoxib administration by evaluating breast tissue needle aspirations, to determine if cell growth can be slowed.
Detailed description
A blind randomized study of celecoxib in women at high risk of developing breast cancer. Subjects are to take twelve months of drug/placebo. At baseline and after twelve months subjects will have a random periareolar fine needle breast aspiration that will be assessed for epithelial cell growth and other markers of risk. Baseline and twelve month serum samples will also be assessed for hormones and growth factors which may be associated with breast cancer risk. Mammograms at baseline and twelve months will also be assessed for breast density changes.
Interventions
DRUGcelecoxib
Celecoxib 400 mg BID
OTHERplacebo
placebo
Sponsors
Susan G. Komen Breast Cancer Foundation
Carol Fabian, MD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* women who have a high risk of breast cancer * older than 18 years
Exclusion criteria
* anticoagulants * marked breast tenderness * pregnant or within twelve months of breast feeding/childbirth
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Percent of Breast Epithelial Cells Staining Positive for Ki-67 | Baseline and 12 months | Immunocytochemical staining of breast epithelial cells. Positive cells reflect proliferative activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mammographic Breast Density | Baseline and 12 months | The percent of mammographic breast area that is considered to be at increased density. Evaluated using the semi-automated computer program Cumulus. |
| Serum Estradiol Concentration | Baseline to 12 months | Change in serum estradiol concentration |
| Serum Sex Hormone Binding Globulin (SHBG) Concentration | Baseline to 12 months | Change in serum concentration |
| Molecular Ratio of Serum Concentration of IGF-1 to IGFBP3 | baseline to 12 months | Change ion ratio. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Celecoxib Celecoxib for six months | 48 |
| Placebo Placebo for six months | 24 |
| Total | 72 |
Baseline characteristics
| Characteristic | Total | Celecoxib | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 72 Participants | 48 Participants | 24 Participants |
| Age, Continuous | 47.5 years STANDARD_DEVIATION 7.4 | 48.7 years STANDARD_DEVIATION 6.6 | 45.2 years STANDARD_DEVIATION 8.5 |
| Region of Enrollment United States | 72 participants | 48 participants | 24 participants |
| Sex: Female, Male Female | 72 Participants | 48 Participants | 24 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 43 / 43 | 21 / 21 |
| serious Total, serious adverse events | 0 / 43 | 0 / 21 |
Outcome results
Primary
Change in Percent of Breast Epithelial Cells Staining Positive for Ki-67
Immunocytochemical staining of breast epithelial cells. Positive cells reflect proliferative activity.
Time frame: Baseline and 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Celecoxib | Change in Percent of Breast Epithelial Cells Staining Positive for Ki-67 | -1.2 percentage of cells staining positive |
| Placebo | Change in Percent of Breast Epithelial Cells Staining Positive for Ki-67 | -2.0 percentage of cells staining positive |
p-value: 0.71Wilcoxon (Mann-Whitney)
Secondary
Mammographic Breast Density
The percent of mammographic breast area that is considered to be at increased density. Evaluated using the semi-automated computer program Cumulus.
Time frame: Baseline and 12 months
Population: Subjects completing 12 months, with baseline and 12 month mammograms suitable for density analysis, such that a change in density over time can be computed
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Celecoxib | Mammographic Breast Density | -1.3 percentage of breast area at increased d | Standard Error 1 |
| Placebo | Mammographic Breast Density | 0.3 percentage of breast area at increased d | Standard Error 1.9 |
Comparison: Difference between groups, two-sided. Endpoint not specifically powered for effect.p-value: 0.053Wilcoxon (Mann-Whitney)
Secondary
Molecular Ratio of Serum Concentration of IGF-1 to IGFBP3
Change ion ratio.
Time frame: baseline to 12 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Celecoxib | Molecular Ratio of Serum Concentration of IGF-1 to IGFBP3 | -0.012 ratio | Standard Error 0.0039 |
| Placebo | Molecular Ratio of Serum Concentration of IGF-1 to IGFBP3 | -0.011 ratio | Standard Error 0.0071 |
p-value: 0.37Wilcoxon (Mann-Whitney)
Secondary
Serum Estradiol Concentration
Change in serum estradiol concentration
Time frame: Baseline to 12 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Celecoxib | Serum Estradiol Concentration | -6.6 pg/ml | Standard Error 5.9 |
| Placebo | Serum Estradiol Concentration | -5.7 pg/ml | Standard Error 11.7 |
p-value: 0.37Wilcoxon (Mann-Whitney)
Secondary
Serum Sex Hormone Binding Globulin (SHBG) Concentration
Change in serum concentration
Time frame: Baseline to 12 months
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Celecoxib | Serum Sex Hormone Binding Globulin (SHBG) Concentration | -0.70 nmol/L | Standard Error 1.61 |
| Placebo | Serum Sex Hormone Binding Globulin (SHBG) Concentration | 3.05 nmol/L | Standard Error 2.16 |
p-value: 0.39Wilcoxon (Mann-Whitney)