A translational clinical trial to demonstrate anti-estrogenic activity of mushrooms

B133

Our group discovered that an extract from the white button mushroom, or Agaricus bisporus, has an aromatase inhibitory effect in a hormone-dependent xenograft murine model, and preliminary data suggest an active phytochemical. With nearly six million female breast cancer survivors in the United States, most of whom are postmenopausal and more than five years after diagnosis, there are numerous long-term breast cancer survivors who remain continuously at risk for second primary breast cancer. Large clinical trials show that aromatase inhibitors not only improve disease free survival from breast cancer recurrence but also are associated with a decreased incidence of second primary breast cancer. Because nutraceuticals are inexpensive, widely-available and generally well-tolerated, and our preclinical data suggest that orally administered white button mushroom extract reduces breast cancer tumor formation via aromatase inhibition, we have designed a translational trial that aims to prove that ingestion of white button mushroom extract will suppress aromatase-mediated estrogen biosynthesis in postmenopausal women who have survived breast cancer. Twenty-four postmenopausal female breast cancer survivors will be assigned to one of four doses of white button mushroom extract in an escalating fashion. Circulating sex steroid hormone levels will be measured pre-treatment and at scheduled intervals during the 12-week treatment period. Mass spectrometry and aromatase inhibition assays will be performed pre-dose and at multiple time points during the first day of treatment to determine pharmacokinetics and pharmacodynamics. Symptom logs will be followed closely throughout the trial. Pre- and post-treatment measurements of lipid profiles and bone metabolism markers will be used as objective early biomarkers of cardiovascular and osteoporotic fracture risk as a result of estrogen deprivation. Biospecimens will be collected before, during and after treatment to allow exploratory evaluation of immunologic endpoints.