Building a Better Tumor-Fighter

Letrozole, a new cancer drug (tradename Femara), worked better at shrinking breast cancer tumors than did the front-line breast cancer drug tamoxifen among a group of postmenopausal women with estrogen-positive tumors, according to a study coordinated by a Duke Medical Center physician.

Sixty percent of women taking letrozole showed tumor shrinkage after four months on the drug, whereas 41 percent of women taking tamoxifen showed tumor shrinkage. Patients taking letrozole also underwent fewer mastectomies (complete breast removal) than women who were taking tamoxifen. Moreover, letrozole actually slowed the rate of cell division, and thus tumor growth, better than tamoxifen did, according to cellular studies conducted on the actual tumors.

Results of the study were presented in December at the annual San Antonio Breast Cancer Symposium. The study was funded by Novartis Pharmaceuticals Corp., which manufactures letrozole.

"We are very excited by letrozole's potential because it appears to block the growth-promoting effects of estrogen within cancer cells better than tamoxifen does," says Mathew Ellis, a Duke oncologist and lead author of the study. "Estrogen is involved in up to 80 percent of all breast cancers, so blocking its effects is vital to successful treatment.

"Although our results are preliminary, letrozole appears to block estrogen more effectively than does tamoxifen, suggesting that letrozole may work for women whose tumors are relatively resistant to tamoxifen."

Letrozole could even replace the more toxic chemotherapy drugs in some patients, or it could be taken together with other non-cytotoxic drugs like Herceptin for maximum effect. Its distinct mechanism of action makes letrozole quite different from current therapies like tamoxifen and other, more toxic chemotherapies, Ellis says.

He cautions that, while his results are highly significant, they must be replicated in larger and more standard types of studies. The current study design was unique because it examined the drugs' ability to shrink tumors before women had surgery to remove their tumors rather than after surgery, as is commonly done to eradicate any undetected cancer cells. Also, the sample size of 324 women is not large enough upon which to base a change in routine clinical practice.

Letrozole works by depriving the tumor of estrogen. Specifically, letrozole inhibits an enzyme called aromatase, which converts the male hormone androgen into the female hormone estrogen. Women taking letrozole, therefore, make almost no estrogen at all. Without estrogen, tumor cells that rely on the hormone for growth cannot divide and do not continue to grow.

Ellis says letrozole's ability to completely block estrogen from the cell is, in part, responsible for its apparent benefits over tamoxifen in some women.