Clinical trial NCT01027416: Analyzing a New Mechanism in Response to Tamoxifen Therapy in Breast Cancer Patients
Official title: Pilot Study to Analyze a Novel Mechanism Underlying Response to Tamoxifen Therapy in Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Keywords: ER positive
Tamoxifen
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2009-12-08
Enrollment: 59
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Mean Percent Positive Proximity Ligation Assays of All Tumor Protein p53-wild Type Breast Tumors in Participants by Treatment Arm
timeFrame: 2 years
Secondary outcomes:
measure: Total Number of Over-expressed Genes, Across All Participants With Tumor Protein p53-wild Type Breast Tumors That Had RNA Samples Available.
timeFrame: 2 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Gokul Das, PhD
role: PRINCIPAL_INVESTIGATOR
References: