White Button Mushroom Extract in Preventing the Recurrence of Breast Cancer in Postmenopausal Breast Cancer Survivors

City of Hope

Status and phase

Completed

Phase 1

Conditions

Breast Cancer

Cancer Survivor

Treatments

Other: laboratory biomarker analysis

Other: high performance liquid chromatography

Other: flow cytometry

Drug: white button mushroom extract

Other: pharmacogenomic studies

Other: pharmacological study

Other: mass spectrometry

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00709020

CHNMC-07213

P30CA033572 (U.S. NIH Grant/Contract)

07213

CDR0000599204 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: White button mushroom extract may stop or delay the recurrence of breast cancer in postmenopausal breast cancer survivors.

PURPOSE: This phase I trial is studying the side effects and best dose of white button mushroom extract in preventing the recurrence of breast cancer in postmenopausal women who are breast cancer survivors.

Full description

OBJECTIVES:

Primary

To show that a whole food extract of white button mushrooms (WBM) can inhibit aromatase-induced estrogen biosynthesis in postmenopausal women who are breast cancer survivors (BCS).
To determine the optimal daily dose of WBM needed to induce aromatase inhibition of estrogen biosynthesis in these patients.
To determine the bioavailability of C-18 unsaturated fatty acids, which are thought to moderate the anticancer effects of WBM.

Secondary

To determine the safety and tolerability of WBM in humans via serial comprehensive symptom questionnaires, pre- and post-treatment markers of bone metabolism, and pre- and post-treatment comprehensive lipid panels.
To explore potential alternate antitumor mechanisms, specifically the effect of WBM on cytokines as well as innate and adaptive cellular immunity.
To describe barriers experienced in recruitment of ethnically diverse subjects from the community into a secondary prevention BCS trial utilizing a dietary supplement intervention in an effort to enhance feasibility of a subsequent phase II trial.

OUTLINE: This is a dose-escalation study.

Patients receive oral white button mushroom extract twice daily for 12 weeks in the absence of a second primary ductal carcinoma in situ, invasive breast cancer, or unacceptable toxicity.

Patients undergo blood and urine sample collection at baseline and periodically during treatment for pharmacokinetic, pharmacodynamic, and immunologic correlative studies. Blood and urine samples are analyzed for concentrations of C-18 unsaturated fatty acids (CUFA) by high-performance liquid chromatography tandem-mass spectrometry. Blood samples are also analyzed for anti-aromatase activity by ex vivo plasma aromatase inhibition assays; circulating sex steroid hormones by radioimmunoassay; serum immune cytokine levels by multiplex cytokine analyses; immunophenotyping, NK-cell activation status, and NK-cell function by multiparameter flow cytometry; lipid levels by lipid assays; and biochemical markers of bone metabolism by bone metabolism marker assays. DNA, RNA, and plasma samples are stored for post-trial pharmacogenomic studies.

Enrollment

16 patients

Sex

Female

Ages

21+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Meets 1 of the following criteria:
- Prior diagnosis of infiltrating carcinoma of the breast ≥ 5 years prior to study entry
- Prior diagnosis of ductal carcinoma in situ
No evidence of disease
Completed all cancer therapy, with the exception of reconstructive surgery, at least 6 months prior to study entry
Meets one of the following criteria:
- Normal mammogram within 1 year of study entry
- Underwent bilateral mastectomy and has been in remission for 5 years, as documented by an oncologist
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
WBC ≥ 3,500/mm³
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9.0 g/dL
Postmenopausal, defined as any of the following:
- Continuous absence of menstruation for 12+ months
- Status post bilateral oophorectomy
- Status post hysterectomy with follicle-stimulating hormone in menopausal range
Creatinine ≤ 1.5 times upper limit of normal (ULN) or less
Total bilirubin ≤ 1.5 times ULN
AST and ALT < 2 times ULN
No allergy to mushrooms
No personal history of any invasive cancer, other than breast cancer, or squamous cell or basal cell skin cancer
No osteoporosis, defined as a bone-mineral density T-score of < -2.5 on dual-energy x-ray absorptiometry scan
No major systemic infections or other major medical illnesses of the cardiovascular, respiratory, or digestive system

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
More than 3 months since prior and no concurrent hormone-modifying medications, including any of the following:
- Oral contraceptives
- Hormone replacement
- Selective estrogen receptor modifiers
- Other aromatase inhibitors
- Gonadotropic-releasing hormone modifiers
At least 1 month since prior and no other concurrent mushroom extracts or DHEA as a dietary supplement
No concurrent therapy, except continued medications for unrelated illness that are not excluded, and necessary medications for unrelated acute illnesses that may occur during the study (e.g., cold, flu, or infection)
No more than 3 concurrent servings per week of the following foods:
- Flaxseeds and flaxseed meal
- High-energy bars or diet bars containing soy or soy protein
- Liquid-nutrition drinks containing soy or soy protein (e.g., Odwalla Future Shake or Ensure Plus)
- Miso soup
- Natto
- Packaged mixed dishes with soy or tofu (e.g., lasagna, burritos, or stir-fry)
- Cooked soybeans or edamame (i.e., green soybeans)
- Roasted soy nuts
- Soymilk, regular or low-fat, plain or flavored
- Soy cheese, such as cheddar, mozzarella, cram cheese, or parmesan (includes all foods made with soy cheese)
- Soy protein powders (e.g., performance or body-builder powders)
- Soy yogurt, all types
- Soy sauce, tamari, teriyaki sauce, Szechuan sauce, or hoisin sauce
- Soy ice cream, tofutti, or other soy desserts
- Tempeh, all types
- Tofu, all types, including low-fat, flavored, marinated, and smoked
- Tofu or soy breakfast sausage, bacon, or other breakfast meat
- Tofu or soy cold cuts, hot dogs, or other deli meat substitutes
- Veggie soy or tofu burger, ground meat substitute (texturized vegetable protein), or soy or tofu, chicken, or turkey
Concurrent supplemental calcium and/or vitamin D and bisphosphonates allowed provided doses remain constant throughout the run-in and treatment portions of the trial