Analyzing a New Mechanism in Response to Tamoxifen Therapy in Breast Cancer Patients



Status:Completed
Conditions:Breast Cancer, Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:12/15/2017
Start Date:December 14, 2009
End Date:December 2015

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Pilot Study to Analyze a Novel Mechanism Underlying Response to Tamoxifen Therapy in Breast Cancer Patients

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.

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.

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)
We found this trial at
2
sites
666 Elm Street
Buffalo, New York 14263
(716) 845-2300
Roswell Park Cancer Institute Welcome to Roswell Park Cancer Institute (RPCI), America's first cancer center...
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5801 South Ellis Avenue
Chicago, Illinois 60637
 773.702.1234
University of Chicago One of the world's premier academic and research institutions, the University of...
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Chicago, IL
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