Breast Cancer
Conditions
Keywords
ER positive, Tamoxifen
Brief summary
This study will help to understand the interaction between estrogen receptor-alpha (ER alpha) and tumor suppressor protein p53 as well as impact on patient tumor gene expression in response to the hormonal therapy Tamoxifen. This information may eventually help select the appropriate therapy for future patients with similar cancer.
Detailed description
Women with abnormal mammogram or suspicious masses will undergo diagnostic core biopsies which will be analyzed for ER/PR and HER2Neu expression. For patients that are ER positive, p53 staining will be done. Women presenting tumors with an Allred score of 3 or greater status will be approached to participate. Women will be randomized to either standard of care surgical therapy or a 4 week intervention of Tamoxifen 20mg daily for 4 weeks prior to surgery. During the intervention, blood draws will be done to measure levels of tamoxifen metabolites in the blood and test for polymorphisms that may decrease levels of active metabolites. Women will undergo two blood draws for PK/PD and one for pharmacogenomics. Tissue microarray (TMA) will be generated from resected tumors for immunohistochemistry (IHC) and proximity ligation assay (PLA) for measuring ER alpha-p53 interaction. Tumor tissue will be used for analyzing tamoxifen metabolites and estradiol levels. RNA and proteins from the tumors will be used for analyzing gene expression.
Interventions
DRUGTamoxifen
Drug: Tamoxifen 20 mg orally 1x/day for 4 weeks
Sponsors
Roswell Park Cancer Institute
National Institutes of Health (NIH)
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The patient must consent to be in the study and must have signed an approved consent form conforming to institutional guidelines 2. The patient must be 18 years or older. 3. Core biopsy should definitively demonstrate invasive carcinoma. 4. Invasive carcinoma should be ER-apha receptor positive 5. The tumor should be approximately at least 1 cm, to account for variability in imaging and imaging occult disease (physical exam, mammography, ultrasound). We recognize that from time to time because of this variation, there might not be enough tissue available for analysis after surgical excision but this will allow the greatest opportunity to capture as many eligible patients as possible. 6. Patients in whom surgical excision of the tumor is part of standard of care management 7. ECOG score of 0 or 1 8. Negative serum or urine beta-hCG pregnancy test at screening for patients of child-bearing potential (this is routinely done if the patient is premenopausal and having surgery) 9. Consent to participate in DBBR (RPCI only)
Exclusion criteria
1. Male patients are not eligible for this study 2. Female patients with inoperable tumors or women with stage 4 disease diagnosed on CT, PET, PET/CT or bone scan. 3. Patients with diagnosis by FNA cytology only 4. Pregnant or lactating women 5. Prior therapy for breast cancer, including irradiation, chemo- immuno- and/or hormonal therapy 6. Patients receiving any hormonal therapy, e.g. ovarian hormonal replacement therapy, infertility medications etc., are not eligible 7. Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude the patient from being subjected to surgical excision 8. Psychiatric or addictive disorders that would preclude obtaining informed consent 9. Patients known or suspected to have hypercoagulable syndrome or with history of venous or arterial thrombosis, stroke, TIA, or pulmonary embolism 10. Women with non-invasive disease or microinvasion are not eligible. 11. Women undergoing neoadjuvant chemotherapy are not eligible 12. women currently on tamoxifen and raloxifene for prevention are not eligible 13. Patients shall not receive any herbal/alternative therapies such as flaxseed or soy products or black cohosh. 14. Patients with a known mutation in p53 (Li Fraumeni Syndrome)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Positive Proximity Ligation Assays of All Tumor Protein p53-wild Type Breast Tumors in Participants by Treatment Arm | 2 years | Status of estrogen receptor alpha (ERά) and tumor protein (p53) interaction in p53-wild type breast tumors in untreated patients verses patients treated with tamoxifen. Mean percent positive polylactide (PLA) of all p53-wild type breast tumors in participants by treatment arm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Over-expressed Genes, Across All Participants With Tumor Protein p53-wild Type Breast Tumors That Had RNA Samples Available. | 2 years | Total number of over-expressed genes, across all participants with tumor protein p53-wild type breast tumors that had ribonucleic acid (RNA) samples available. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORGokul Das, PhD
Roswell Park Cancer Institute
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| No Intervention No Intervention: Standard of care | 31 |
| Tamoxifen Tamoxifen 20 mg orally 1x/day for 4 weeks
Tamoxifen: Drug: Tamoxifen 20 mg orally 1x/day for 4 weeks | 28 |
| Total | 59 |
Baseline characteristics
| Characteristic | No Intervention | Tamoxifen | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 9 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 19 Participants | 44 Participants |
| Age, Continuous | 55.7 years STANDARD_DEVIATION 11.1 | 58.5 years STANDARD_DEVIATION 12.4 | 57.0 years STANDARD_DEVIATION 11.7 |
| 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 | 3 Participants | 4 Participants | 7 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 | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 27 Participants | 23 Participants | 50 Participants |
| Sex: Female, Male Female | 31 Participants | 28 Participants | 59 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| other Total, other adverse events | 0 / 31 | 19 / 28 |
| serious Total, serious adverse events | 1 / 31 | 0 / 28 |
Outcome results
Primary
Mean Percent Positive Proximity Ligation Assays of All Tumor Protein p53-wild Type Breast Tumors in Participants by Treatment Arm
Status of estrogen receptor alpha (ERά) and tumor protein (p53) interaction in p53-wild type breast tumors in untreated patients verses patients treated with tamoxifen. Mean percent positive polylactide (PLA) of all p53-wild type breast tumors in participants by treatment arm
Time frame: 2 years
Population: All patients with p53-wild type breast tumors
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Intervention | Mean Percent Positive Proximity Ligation Assays of All Tumor Protein p53-wild Type Breast Tumors in Participants by Treatment Arm | 27.0 percentage of positive PLA | Standard Deviation 34.4 |
| Tamoxifen | Mean Percent Positive Proximity Ligation Assays of All Tumor Protein p53-wild Type Breast Tumors in Participants by Treatment Arm | 4.4 percentage of positive PLA | Standard Deviation 4.4 |
Secondary
Total Number of Over-expressed Genes, Across All Participants With Tumor Protein p53-wild Type Breast Tumors That Had RNA Samples Available.
Total number of over-expressed genes, across all participants with tumor protein p53-wild type breast tumors that had ribonucleic acid (RNA) samples available.
Time frame: 2 years
Population: All patients with p53-wild type breast tumors that had RNA samples available
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| No Intervention | Total Number of Over-expressed Genes, Across All Participants With Tumor Protein p53-wild Type Breast Tumors That Had RNA Samples Available. | 196 genes |
| Tamoxifen | Total Number of Over-expressed Genes, Across All Participants With Tumor Protein p53-wild Type Breast Tumors That Had RNA Samples Available. | 256 genes |