Risk of Rare Uterine Cancers Increases Following Use of Tamoxifen

Women who were initially treated with tamoxifen for breast cancer are at an increased risk of rare cancers of the uterus, according to a study published in the January 7, 2004, Journal of the National Cancer Institute.

Rochelle E. Curtis and colleagues from the NCI's Division of Cancer Epidemiology and Genetics found that women who took tamoxifen were four times more likely to develop malignant mixed mullerian tumors (MMMTs) of the uterus as compared to women in the general population. Tamoxifen-treated women were also twice as likely to develop endometrial adenocarcinoma of the uterus, in agreement with results reported in previous studies.

"However, it is important to recognize that the absolute risk of a woman developing MMMT is small," Curtis said, "because these tumors are so rare." For every 10,000 women who took tamoxifen to treat their cancer, an additional 1.4 MMMT cases per year were reported, compared to an additional 8.4 cases per 10,000 women per year for endometrial adenocarcinomas, Curtis said.

"We know more about tamoxifen than we do about any other drug used to treat and prevent breast cancer," said Dr. Leslie Ford, associate director for clinical research, Division of Cancer Prevention. "These results are similar to what we have found in clinical trials and are included in information provided to women considering tamoxifen therapy. It is important for women taking this drug to make informed choices."

Curtis and her colleagues used the cancer registries of the Surveillance, Epidemiology, and End Results Program to follow nearly 39,500 women who were diagnosed from 1980 through 2000, and who had not received initial chemotherapy.

The registry data also showed that after the initial diagnosis of breast cancer, MMMTs tended to be detected later than endometrial adenocarcinomas (7.5 years vs. four to five years). The MMMTs that developed after breast cancer were aggressive tumors with generally poor prognosis.

"Despite limited evidence that MMMTs and endometrial adenocarcinomas may share reproductive and hormonal risk factors, the mechanisms underlying tamoxifen-related MMMTs are unclear," said Curtis. "These findings indicate that tamoxifen may have delayed effects in some patients, such as the heightened risk of MMMT."

Anastrozole May Benefit Some Women More Than Tamoxifen

Postmenopausal women with breast cancer who were switched from tamoxifen to a newer drug, anastrozole (Arimidex®), were less likely to die or to have a relapse of their disease than women who continued to take tamoxifen. These preliminary findings were presented by Dr. Francesco Boccardo, of the National Institute of Cancer Research, in Genoa, Italy, at the San Antonio Breast Cancer Symposium, December 3, 2003.

A total of 426 women who had been taking tamoxifen for two years or more were randomly assigned to continue on tamoxifen for up to five years or to switch to anastrozole for a comparable period of time. All of the women had had surgery for breast cancer that had spread to the lymph nodes. All had tumors that were positive for the estrogen receptor. Women were followed for a median of two years.

Of 218 women assigned to continue taking tamoxifen, 26 (12 percent) have had a recurrence of breast cancer, been diagnosed with a second primary cancer, or died. Of 208 women assigned to take anastrozole, 10 (5 percent) have had a recurrence of breast cancer or been diagnosed with a second cancer, and none has died.

Although the results of this study are encouraging, longer follow-up is needed before it can be concluded that anastrozole is superior to tamoxifen, according to Dr. Jennifer Eng-Wong, a medical oncologist at the National Cancer Institute.

Imatinib Inhibits the Growth of Neuroblastoma Cells

The cancer drug imatinib (Gleevec™) shows promise against neuroblastoma, the most common solid extracranial tumor of early childhood, according to a study in the January 7, 2004, issue of the Journal of the National Cancer Institute. In culture and in a mouse model, imatinib inhibited the growth of neuroblastoma cells, reported the research team led by Dr. Carol J. Thiele of NCI's Pediatric Oncology Branch.