Breast Cancer
Conditions
Keywords
proliferation Index, Tamoxifen, Fulvestrant, cyclinD1, Breast cancer
Brief summary
The purpose of this study is to microscopically examine breast cancer cells of pre-menopausal and post-menopausal women before and after exposure to one of the two commonly used breast cancer drugs, tamoxifen or fulvestrant.
Detailed description
The researchers hypothesize that the cyclinD1-interactome can be used to orient the use of fulvestrant in premenopausal and postmenopausal women. To test this hypothesis, the researchers propose a pre-surgical randomized clinical trial of tamoxifen vs fulvestrant in the window between breast cancer diagnosis on core biopsy and definitive surgery. Women with ER/cyclinD1 positive tumors will be eligible. Response to tamoxifen or fulvestrant will be evaluated using standard proliferation index as well as gene expression signatures obtained in pre-clinical models of tamoxifen resistance and sensitivity to fulvestrant. In addition, the researchers propose to use cutting edge new technology allowing ex-vivo expansion of primary culture from only a few cancer cells obtained by fine needle biopsy. The researchers propose to compare the response of these primary cells to patient response. If successful, the impact of this work can support the expansion of use of fulvestrant to not only postmenopausal women but premenopausal women as well. In addition, it may serve as a proof of principle to maximize the use of biopsy material to predict treatment response
Interventions
DRUGFulvestrant
fulvestrant 750 mg (three 5 ml injections slowly over 1-2 mn per injection in the buttocks) on day 1 only
DRUGTamoxifen
14 days of treatment with tamoxifen 20mg orally each day
Sponsors
AstraZeneca
Icahn School of Medicine at Mount Sinai
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the study treatment regimen and follow-up, must be obtained and documented according to the local regulatory requirements * Adult women greater than 18 years old * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 * New diagnosis of invasive cyclin D1 +, ER+, PR +/-, Her2- breast cancer * Cyclin D1 positive as defined as a total immunohistochemical score of 5 or greater * Hormone receptor positive as defined as ≥ 10% positive stained cells * HER2-normal (IHC score 0-1 or FISH negative \[in-situ hybridization (ISH) ratio \<= 2.0 status\]) * Tumor size at least 5 mm with planned primary surgery at Mount Sinai * A negative urine dipstick pregnancy test
Exclusion criteria
* Estrogen receptor negative invasive breast carcinoma as defined as less than 10% stained cells * Prior antiestrogen therapy * Tumor size less than 5 mm * Prior diagnosis of thrombosis or known hypercoagulable state * Known history of bleeding diathesis * Known liver disease * Prior treatment with neoadjuvant therapy * Inflammatory breast cancer defined as clinically significant erythema of the breast and/or documented dermal lymphatic invasion (not direct skin invasion by tumor or peau d'orange without erythema). * Current severe or uncontrolled systemic disease * Pregnancy or lactation period. Patients of childbearing potential must implement adequate non-hormonal contraceptive measures (barrier methods, intrauterine contraceptive devices) during study treatment. * Prior malignancy (including invasive or ductal in-situ breast cancer) within 5 years prior to randomization, except curatively treated basal cell carcinoma of the skin and carcinoma in situ of the cervix.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ki67 Cell Percentage | baseline and 2 weeks | The change in proliferation index as measured by the percentage of cells staining for Ki67 at 2 weeks as compared on baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Progesterone Receptor Level | baseline and 2 weeks | The change in progesterone receptor level at 2 weeks as compared to baseline. |
| Incidence of Tamoxifen-resistance Gene Expression | 2 weeks | Number of tamoxifen-resistance gene expression signature observed in patients with cyclinD1 overexpressing breast cancers. |
| Change in Estrogen Receptor Level | baseline and 2 weeks | The change in estrogen receptor level at 2 weeks as compared to baseline. |
| Drug Dose Level | 2 weeks | For samples that are available for culture in vivo, proliferation assay to test whether the cells derived from individual patients respond the same as the tumor in vivo in the same patient. |
| Percentage of Cells Staining Positive Within the Breast Tumor | 2 weeks | Differential treatment effect for pre and post menopausal subjects assessed by the mean change in levels (expressed as a percentage of cells staining positive within the breast tumor) of ER (and PR) between pre-treatment and post-treatment stratified by menopausal status. |
| Incidence of Fulvestrant-sensitivity Gene Expression | 2 weeks | Number of fulvestrant-sensitivity gene expression signature observed in patients with cyclinD1 overexpressing breast cancers. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fulvestrant 750 mg injection in 3 divided doses
Fulvestrant: fulvestrant 750 mg (three 5 ml injections slowly over 1-2 mn per injection in the buttocks) on day 1 only | 0 |
| Tamoxifen 20mg orally
Tamoxifen: 14 days of treatment with tamoxifen 20mg orally each day | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Fulvestrant | Tamoxifen | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 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 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Change in Ki67 Cell Percentage
The change in proliferation index as measured by the percentage of cells staining for Ki67 at 2 weeks as compared on baseline.
Time frame: baseline and 2 weeks
Population: With the 2 patients enrolled on the trial, the data collected was insufficient and not evaluable.
Secondary
Change in Estrogen Receptor Level
The change in estrogen receptor level at 2 weeks as compared to baseline.
Time frame: baseline and 2 weeks
Population: With the 2 patients enrolled on the trial, the data collected was insufficient and not evaluable.
Secondary
Change in Progesterone Receptor Level
The change in progesterone receptor level at 2 weeks as compared to baseline.
Time frame: baseline and 2 weeks
Population: With the 2 patients enrolled on the trial, the data collected was insufficient and not evaluable.
Secondary
Drug Dose Level
For samples that are available for culture in vivo, proliferation assay to test whether the cells derived from individual patients respond the same as the tumor in vivo in the same patient.
Time frame: 2 weeks
Population: With the 2 patients enrolled on the trial, the data collected was insufficient and not evaluable.
Secondary
Incidence of Fulvestrant-sensitivity Gene Expression
Number of fulvestrant-sensitivity gene expression signature observed in patients with cyclinD1 overexpressing breast cancers.
Time frame: 2 weeks
Population: With the 2 patients enrolled on the trial, the data collected was insufficient and not evaluable.
Secondary
Incidence of Tamoxifen-resistance Gene Expression
Number of tamoxifen-resistance gene expression signature observed in patients with cyclinD1 overexpressing breast cancers.
Time frame: 2 weeks
Population: With the 2 patients enrolled on the trial, the data collected was insufficient and not evaluable.
Secondary
Percentage of Cells Staining Positive Within the Breast Tumor
Differential treatment effect for pre and post menopausal subjects assessed by the mean change in levels (expressed as a percentage of cells staining positive within the breast tumor) of ER (and PR) between pre-treatment and post-treatment stratified by menopausal status.
Time frame: 2 weeks
Population: With the 2 patients enrolled on the trial, the data collected was insufficient and not evaluable.