Trial Tests Drug s Ability to Prevent Breast Cancer in High-Risk Women

CINCINNATI—Breast cancer specialists at the University of Cincinnati (UC) believe that a drug currently used to treat certain types of breast cancer may also help prevent the disease from ever developing in the women who are most vulnerable to it.

Led locally by Zeina Nahleh, MD, this national, phase-3 clinical trial will determine whether exemestane (Aromasin) can prevent the disease in high-risk, postmenopausal women.

Exemestane, approved by the Food and Drug Administration for the treatment of what is known as hormone-receptor-positive breast cancer, is an aromatase inhibitor, a class of drug that works by blocking the enzymes that produce the natural female hormone estrogen. Previous research has shown estrogen promotes the growth of most types of breast cancer.

The latest approach to breast cancer prevention for patients at elevated risk focuses on “chemopreventive” drugs like exemestane that reduce the amount of estrogen produced in the body and, consequently, slow estrogen-dependent tumor growth.

“We know exemestane is an effective treatment for existing estrogen-dependent breast cancer,” says Nahleh, assistant professor and director of medical breast oncology program in UC’s division of hematology and oncology. “Now we want to know if the same chemopreventive drug can halt breast cancer development in high-risk women.”

“There’s a continuum of breast cancer prevention options for high-risk women—ranging from increased screening to the most aggressive choice of prophylactic surgery,” adds Jennifer Manders, MD, an assistant professor of surgery at UC and coinvestigator of the study in Cincinnati. “And chemopreventive drugs are right in the middle.”

Currently, women who are at high risk of developing breast cancer can take tamoxifen (Nolvadex), an oral medication that blocks the effects of estrogen in the cells and minimizes estrogen in the body, as a preventive measure.

“Tamoxifen has been the only chemoprevention option we've had for reducing the occurrence of breast cancer in high-risk women,” explains Nahleh, “but many patients hesitate to take it for fear of serious—though infrequent—side effects.”

Those side effects include an increased risk for blood clots, endometrial cancers and significant weight gain.

“Ultimately,” adds Manders, “it’s up to the patient to decide how much risk she can tolerate, and then balance her risk for developing breast cancer with the potential side effects of preventive medicine.”

If exemestane can substantially reduce the incidence of breast cancer, the researchers add, it will give high-risk women another prevention option that yields fewer negative side effects.

Trial participants are randomized to take either exemestane or a placebo by mouth daily for five years. Physicians conduct biannual checkups of study participants to analyze blood samples and screen for signs of breast cancer.

Before treatment begins, participants undergo a bone mineral test to determine if they are at elevated risk for low bone density (osteopenia) and bone fragility (osteoporosis). Those who are at risk may receive medications in addition to vitamin D or calcium supplements to offset any density-reducing effects of the trial medication.

The UC researchers stress that only postmenopausal women over 40 who are considered at high risk for breast cancer are eligible for this trial. Risk is calculated on the basis of age, family history of breast cancer, personal medical history, and age at first menstrual cycle and at first live childbirth.

According to the American Cancer Society, more than 212,900 women—about 9,600 of them Ohioans—will be diagnosed with breast cancer in 2006. Invasive breast cancer, which starts in the milk ducts and invades the surrounding fatty tissue of the breast, accounts for 80 percent of all cases.

This trial is sponsored by the National Cancer Institute of Canada. Medications are provided at no cost to study participants by Pfizer Pharmaceuticals. Neither Nahleh nor Manders have any financial interest in Pfizer Pharmaceuticals.

For more information on UC Cancer Center breast cancer clinical trials call (513) 584-2951.