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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Tamoxifen

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.

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60601
      • University of Chicago
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No Intervention
Active Comparator: Tamoxifen; Tamoxifen 20 mg orally 1x/day for 4 weeks	Drug: Tamoxifen; Drug: Tamoxifen 20 mg orally 1x/day for 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 years

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Gokul Das, PhD, Roswell Park Cancer Institute

Publications and helpful links

General Publications

• Oturkar CC, Rosario SR, Hutson AD, Groman A, Edge SB, Morrison CD, Swetzig WM, Wang J, Park JH, Kaipparettu BA, Singh PK, Kumar S, Cappuccino HH, Ranjan M, Adjei A, Ghasemi M, Goey AKL, Kulkarni S, Das GM. ESR1 and p53 interactome alteration defines mechanisms of tamoxifen response in luminal breast cancer. iScience. 2024 May 15;27(6):109995. doi: 10.1016/j.isci.2024.109995. eCollection 2024 Jun 21.

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2009
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: December 4, 2009
• First Submitted That Met QC Criteria: December 4, 2009
• First Posted (Estimated): December 8, 2009

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Tamoxifen; ER positive
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Benzene Derivatives; Stilbenes; Benzylidene Compounds; Tamoxifen
• Other Study ID Numbers: RPCI I 110907; R21CA137635-01A1 (U.S. NIH Grant/Contract)