DHEA in Treating Women Undergoing Surgery for Stage I, Stage II, or Stage III Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Dehydroepiandrosterone (DHEA) may slow the growth of tumor cells and be an effective treatment for women with breast cancer. PURPOSE: This phase I trial is studying how well DHEA works in treating women undergoing surgery for stage I, stage II, or stage III breast cancer.

Detailed Description
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OBJECTIVES: Primary To identify the effect of the adrenal steroid, dehydroepiandrosterone (DHEA), on tumor proliferation in women with estrogen receptor-negative, progesterone receptor-negative, HER2/neu-negative, and androgen receptor (AR)-positive stage I-III adenocarcinoma of the breast. Secondary To study the effect of DHEA on expression of AR in these patients. To assess the effect of DHEA on changes in serum estrogen and androgen hormone levels (e.g., estrone, estradiol, testosterone, dihydrotestosterone, DHEA, and DHEA-sulfate) in these patients. To assess the toxicity of DHEA in these patients. To follow the clinical course of these patients. OUTLINE: Patients receive oral dehydroepiandrosterone (DHEA) twice daily on days -14 to 0. Patients then undergo surgery on day 1. Tissue samples are collected at baseline and at the time of surgery for biomarker analysis (androgen receptor, estrogen receptor, progesterone receptor, HER2/neu, Ki-67, and p53) by IHC. Blood samples are collected at baseline and after completion of treatment with DHEA for analysis of serum hormone (e.g., estrone, estradiol, testosterone, dihydrotestosterone, DHEA, and DHEA-sulfate) and cytokine levels. After completion of study therapy, patients are followed up at 1 week and then every 6 months for 3 years.

Official Title
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A Pilot Study of Androgen Receptor as a Target for the Treatment of ER-/PR-/AR + Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: DHEA
* Procedure: Surgical resection


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed invasive adenocarcinoma of the breast Stage I (T1c), II, or III disease (AJCC staging system) Lesion ≥ 1 cm on breast imaging studies (mammogram, ultrasound, or MRI) HER2/neu-negative tumor Planning to receive dehydroepiandrosterone (DHEA) prior to surgery Disease amenable to surgery with curative intent Scheduled to undergo surgery immediately after completion of DHEA No locally advanced or metastatic disease not amenable to surgery Hormone receptor status: Estrogen receptor- and progesterone receptor-negative tumor Androgen receptor-positive tumor PATIENT CHARACTERISTICS: Menopausal status not specified ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% ANC ≥ 1,000/mm^3 Platelet count ≥ 75,000/mm^3 AST and ALT ≤ 2.5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN Bilirubin ≤ 2 times ULN Hemoglobin > 9 g/dL Creatinine normal OR creatinine clearance ≥ 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for ≥ 1 week after completion of study therapy No history of allergic reactions attributed to compounds of similar chemical or biological composition to DHEA or anastrozole No concurrent uncontrolled illness, including but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Psychiatric illness or social situation that would limit compliance with study requirements PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 5 years since prior surgery, radiotherapy, biological therapy, hormone therapy, and/or chemotherapy for invasive breast cancer No other concurrent antineoplastic or antitumor agents No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DHEA, surgical resection<br>Day-14 (approx. 2 wks prior to surgery): begin a 2 week course of DHEA; Day-7 (approx. 1 wk after starting treatment): answer question about pill diary; Day 0 (approx. 2 wks after starting treatment, within 48 hours prior to surgery; | Drug: DHEA<br>* DHEA administration will begin approxiately 14 days prior to surgery.<br>* Other names: therapeutic dehydroepiandrosterone;Procedure: Surgical resection<br>* Surgical procedure of the invasive breast cancer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Proliferation (Percentage of Ki-67 Positive Cells) |  | Baseline, prior to DHEA treatment, within 48 hours prior to surgery and after 14 days of DHEA treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Dehydroepiandrosterone (DHEA) on Androgen Receptor Expression |  | Baseline, prior to DHEA treatment, within 48 hours prior to surgery and after 14 days of DHEA treatment. | 
| Effect of DHEA on Changes in Serum Estrogen and Androgen Hormone Levels (e.g., Estrone, Estradiol, Testosterone, Dihydrotestosterone, DHEA, and DHEA-sulfate) |  | Baseline, prior to DHEA treatment, within 48 hours prior to surgery and after 14 days of DHEA treatment. | 
| Toxicity |  | Within 48 hours prior to surgery and after 14 days of DHEA treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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triple-negative breast cancer, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer