Different Doses Of Hormone DHEA May Combat Certain Breast Cancers

02/23/11  Portland, Ore.

Researchers at the Oregon Health & Science University Cancer Institute are looking at how the hormone DHEA, affects certain breast cancers.

In the lab researchers noticed that when they put DHEA on estrogen-receptor-negative and progesterone-receptor-negative breast cancer cells, the cells died. This was not what they expected.  They thought there would be no reaction because the cells lack all the hormone receptors usually tested for in breast cancer, according to the principal investigator Rodney Pommier, M.D., OHSU Cancer Institute member.

DHEA (Dehydroepiandrosterone) is a naturally occurring, weak hormone secreted by the adrenal gland and serves as precursor to male and female sex hormones, androgens and estrogens.

SuEllen Pommier, Ph.D., subsequently showed in the laboratory that the DHEA signaled the cells to die by binding to the androgen receptor. This receptor is not routinely part of breast cancer testing, but it is often present, even in those that lack all other hormone receptors. The Pommiers are a husband-and-wife team researching the causes of breast cancer and developing new treatments for the disease.

“We are encouraged by the fact that the androgen receptor is expressed in a significant number of cases of breast cancer. This means that we have another tool in our arsenal to combat estrogen- receptor-negative breast cancer,” said SuEllen Pommier, professor of surgery, (general surgery), OHSU School of Medicine. 

To further this research, the Pommiers and colleagues want to see if this observation can be developed into a nontoxic hormonal therapy for women with estrogen-receptor- negative/progesterone-receptor-negative but androgen-receptor-positive breast cancer. There has not been any effective hormone therapy for these patients because all hormone therapies target the estrogen receptors. Standard treatment for patients whose tumors lack estrogen and progesterone receptors has been chemotherapy.

The researchers are hoping to enroll 29 breast cancer patients, who meet specific criteria, in this new study to determine the maximum tolerable dose of DHEA that causes a tumor response in patients whose tumors are estrogen- and progesterone-receptor-negative and also are androgen-receptor-positive.

“We hope to find out if DHEA treatment, which will be given in a pill form, will shrink this type of tumor. This would add a non-toxic, hormonal treatment option in addition to chemotherapy. We think this treatment has a good chance of shrinking metastatic tumors, even when chemotherapy is no longer working. It could potentially add years to a woman’s or a man’s life,” said Rodney Pommier, professor of surgery, division of general surgery, OHSU School of Medicine.

Estrogen/progesterone-receptor-negative tumors mean that manipulation of the estrogen and progesterone receptors will not slow the growth or spread of the cancer cells. Androgen-receptor-positive means there is a molecule on the cancer cells that binds male hormones like testosterone that can still be manipulated to control the cancer. These cancers account for about one-third of breast cancers, or some 65,000 a year in the United States. The genetic mutation BRC1 tends to have estrogen/progesterone-negative receptors. This type of tumor also tends to affect younger women and is considerably more difficult to treat. However, many patients diagnosed with estrogen/progesterone-negative breast cancers are often not further screened to determine if their cancer is also androgen-receptor-positive.

“We are using DHEA as our hormone to signal the androgen receptor rather than testosterone because we think it will have fewer side effects such as acne, body hair growth and hair thinning.  Also, studies have shown people have a sense of well-being and increased energy when they take DHEA,” Rodney Pommier said.

The two-year study is funded by the National Institutes of Health.
 
Other researchers involved include: Shiuh-Wen Luoh, M.D., Ph.D., assistant professor of medicine, (hematology/medical oncology); Joseph Bubalo, Pharm.D., assistant professor of medicine, (hematology and medical oncology); Dennis Koop, Ph.D., professor of physiology and pharmacology; Motomi Mori, Ph.D., professor of public health and preventive medicine, all OHSU School of Medicine and OHSU Cancer Institute members.

To be considered for the study, please call 503 494-3078.

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The OHSU Cancer Institute is the only cancer center designated by the National Cancer Institute center between Sacramento and Seattle. It comprises some 120 clinical researchers, basic scientists and population scientists who work together to translate scientific discoveries into longer and better lives for Oregon's cancer patients. In the lab, basic scientists examine cancer cells and normal cells to uncover molecular abnormalities that cause the disease. This basic science informs more than 200 clinical trials conducted at the OHSU Cancer Institute.