Can exemestane prevent breast cancer?

Canadian-coordinated ExCel trial aims to find out
if new drug will top tamoxifen

By Tony Craig

"My own feeling about this trial is that it's going to be positive," says Dr Eric Winquist, one of the primary investigators of the ExCel trial and an oncologist at the London Health Sciences Centre.

ExCel, coordinated by the National Cancer Institute of Canada and launched a month ago, will follow more than 4,500 postmenopausal women from this country, the US and Spain over a five-year period. All subjects will have to be over 35 with an increased risk of breast cancer due to family history or age factors.

Exemestane has been approved in Canada since 2000 for the prevention of breast cancer recurrence in post- menopausal women. It has a proven track record and a paper published March 11, 2004 in the New England Journal of Medicine convincingly demonstrated the drug's ability to prevent contralateral tumours in women treated for cancer in one breast. In fact, secondary tumours were only half as common in women taking exemestane as in those taking tamoxifen — the treatment currently approved for the prevention of primary breast tumours.

"The data we have from clinical trials is good or better than tamoxifen," says Dr Winquist. He adds that tamoxifen's side effects like vaginal bleeding, blood clots and an increased risk of uterine cancer are often unacceptable to both doctors and patients.

Exemestane isn't without its own set of side effects. "The main thing with exemestane use has been hot flashes, minor aches and pain," says Dr Winquist. Also, because "there has been some concern that this class of drugs can cause some bone loss," researchers will be watching bone mineral density very carefully and keeping track of fracture rates throughout the course of the trial.

SERM DIFFERENCE
Exemestane belongs to the class of drugs known as aromatase inhibitors. Unlike tamoxifen, a selective estrogen receptor modulator (SERM), aromatase inhibitors don't block estrogen's interaction with cancer cells. Rather, they interfere with the body's production of this hormone, leaving less for cancer cells to bind with. Aromatase inhibitors prevent the adrenal gland from converting androgen to estrogen, the primary source of the hormone in postmenopausal women. This means that unlike tamoxifen, aromatase inhibitors are largely useless in premenopausal women, who produce most of their estrogen directly from the ovaries.

Another aromatase inhibitor, anastrozole, proved significantly more effective than tamoxifen in preventing tumour recurrence in postmenopausal women in the 2002 ATAC trial — the largest-ever breast cancer treatment trial. Like exemestane, anastrozole produced fewer side effects like hot flushes and endometrial cancer. One notable result of that trial was that patients who took tamoxifen and anastrozole together fared worse than either monotherapy group.

PROMISING PREDICTIONS
Part of the goal of ExCel, explains Dr Winquist, is to identify the women who would benefit most from exemestane. Researchers will look at three specific groups of postmenopausal women; those over 60; women under 60 at high risk for breast cancer; and those who have some history of pre-cancer lesions of the breast. "The effects of exemestane might prove to be more profound in one group over another," says Dr Winquist. He believes that there might be some positive preliminary results as early as two to three years into the trial. Only time will tell. "I will be honest," he adds, "I think that this drug is going to prevent breast cancer." It would be wise to keep an eye on this drug's performance as the ExCel trial unfolds over the next few years to see if Dr Winquist's prediction is accurate.

— Additional reporting by Julia Cyboran