Behold the formidable fungus. Not quite plant and not quite animal, it grows in out-of-the-way spots, avoiding attention. But if new studies at City of Hope bear fruit, the White button mushroom may enter the spotlight.

City of Hope researchers are speeding findings about mushrooms' cancer-fighting properties from the lab to clinical trials. After showing that mushroom extract slows breast cancer growth in mice, the team will soon begin human clinical studies involving breast and prostate cancers.
They hope to offer men and women a way to reduce cancer risk--or even stunt cancer growth--through an addition to their diet. The potential is so enticing that the California Breast Cancer Research Program, the American Institute for Cancer Research and the National Institutes of Health supported the lab studies, and the Mushroom Council recently donated $560,000 to support the pilot clinical trials.

"Eating mushrooms would be an easy intervention," said Shiuan Chen, Ph.D., director of the Department of Surgical Research and leader of the mushroom project. "It could provide a cost-effective, whole-food option for cancer risk reduction."

Chen began investigating mushrooms because his lab's studies found that ingredients in the mushrooms suppressed the effects of a natural substance in the body called aromatase. Blocking aromatase is a key way that physicians reduce circulating estrogen levels among their postmenopausal patients. That is important because about 75 percent of postmenopausal women with breast cancer have tumors that depend on estrogen to grow.

"We've seen that aromatase-inhibiting drugs are helpful in preventing recurrence in postmenopausal women with breast cancer," said Melanie Palomares, M.D., M.S., assistant professor of medical oncology and population sciences, "and breast cancer survivors were found to develop fewer new breast cancers too."

Physicians currently recommend that postmenopausal women with hormone-responsive breast cancer take these drugs for two to five years.

"At the end of this period, women can feel unsure about what to do next," Chen said. "If mushrooms can reduce risk, perhaps we can tell them to eat mushrooms instead." That is the idea behind a phase I clinical trial led by Palomares.

Palomares and colleagues soon will recruit 24 postmenopausal breast cancer survivors for this study. Women who were diagnosed with breast cancer five or more years ago and remain free of disease will be randomly assigned to take between five and 13 grams of freeze-dried White button mushrooms in tablet form daily for 12 weeks.

Researchers will monitor aromatase activity and female hormones in participants, as well as levels of conjugated linoleic acids, a group of compounds in the mushrooms that appear to be responsible for their anticancer properties. They also will study effects osn the immune system, cholesterol and bone health. Laura Dorr-Uyemura, R.D., director of clinical nutrition, created a food questionnaire to monitor patients' eating habits during the trial.

A second planned trial, mean-while, investigates mushrooms' potential in prostate cancer.

Przemyslaw W. Twardowski, M.D., assistant professor of medical oncology, explains that physicians have no clear answer on how to treat a specific group of prostate cancer patients: men who were treated for cancer and appear to be cancer-free on imaging scans, but whose prostate-specific antigen (PSA) levels have begun to rise. Cancer usually returns in these patients.

"There is much interest in a natural product that could intervene in this early stage and at least delay the need for other toxic therapies," Twardowski said.

Laboratory research has shown that mushroom extract can lower levels of 5-alpha reductase, an enzyme linked to male hormones involved in prostate cancer.

For their clinical trial, the researchers plan to monitor patients for aromatase activity, male hormone levels, levels of conjugated linoleic acids and other substances, as well as effects on the immune system. They also potentially may check for circulating tumor cells in the blood.

Michael Kalos, Ph.D., director of the Clinical Immunobiology Correlative Studies Laboratory, will help assess immune activity, while Timothy W. Synold, Pharm.D., will run tests to track levels of mushroom-related compounds in participants. Senior Biostatistician Paul Frankel, Ph.D., Pharmacy's Sharon Denison, Pharm.D., and Yate-Ching Yuan, Ph.D., of the Department of Biomedical Informatics, will participate as well.

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Kimlin Tam Ashing--Giwa, Ph.D., professor of population sciences and director of the Center of Community Alliance for Research & Education, will focus on community inclusion and the recruitment of diverse breast cancer survivors.

"The beautiful thing about dietary trials is they are so practical," Ashing-Giwa said. "It gives the community hope that there are more acceptable, natural ways of fighting cancer. It's easier to bring these kinds of studies to the community."

Alicia Di Rado

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