Breast Cancer
Conditions
Keywords
triple-negative breast cancer, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
Brief summary
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
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.
Interventions
DRUGDHEA
DHEA administration will begin approxiately 14 days prior to surgery.
PROCEDURESurgical resection
Surgical procedure of the invasive breast cancer
Sponsors
National Cancer Institute (NCI)
Barbara Ann Karmanos Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | 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
| Measure | 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. |
Countries
United States
Participant flow
Recruitment details
Cancer center clinic
Participants by arm
| Arm | Count |
|---|---|
| DHEA, Surgical Resection 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;
DHEA : DHEA administration will begin approxiately 14 days prior to surgery.
Surgical resection : Surgical procedure of the invasive breast cancer | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | DHEA, Surgical Resection |
|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 0 |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
Tumor Proliferation (Percentage of Ki-67 Positive Cells)
Time frame: Baseline, prior to DHEA treatment, within 48 hours prior to surgery and after 14 days of DHEA treatment.
Population: Per protocol, although no analysis was completed, patient chose to receive neoadjuvant chemo instead of surgery \& refused follow up.
Secondary
Effect of Dehydroepiandrosterone (DHEA) on Androgen Receptor Expression
Time frame: Baseline, prior to DHEA treatment, within 48 hours prior to surgery and after 14 days of DHEA treatment.
Population: Per protocol, although no analysis was completed, patient chose to receive neoadjuvant chemo instead of surgery \& refused follow up.
Secondary
Effect of DHEA on Changes in Serum Estrogen and Androgen Hormone Levels (e.g., Estrone, Estradiol, Testosterone, Dihydrotestosterone, DHEA, and DHEA-sulfate)
Time frame: Baseline, prior to DHEA treatment, within 48 hours prior to surgery and after 14 days of DHEA treatment.
Population: Per protocol, although no analysis was completed, patient chose to receive neoadjuvant chemo instead of surgery \& refused follow up.
Secondary
Toxicity
Time frame: Within 48 hours prior to surgery and after 14 days of DHEA treatment.
Population: Per protocol, although no analysis was completed, patient chose to receive neoadjuvant chemo instead of surgery \& refused follow up.