Anastrozole (Arimidex®) Outperforms Tamoxifen

Drug is Safer in Preventing Breast Cancer Recurrence

The drug anastrozole (Arimidex) now replaces tamoxifen as the recommended treatment to help prevent recurrence of breast cancer in postmenopausal women with hormone receptor-positive breast cancer, according to a landmark study that found the first drug more effective and safer than the long-time standard.

"These results have changed the practice of medicine and treatment for this subset of patients," says the trial's principal U.S. investigator Aman Buzdar, M.D., professor in the Department of Breast Medical Oncology at M. D. Anderson.

The study results, published online Dec. 8 in the British medical journal The Lancet, show that anastrozole further reduces the risk of breast cancer returning in this group of women by 26%, above the 50% already achieved by tamoxifen. About three-fourths of postmenopausal women with breast cancer are hormone receptor-positive, meaning their tumors are fueled by hormones.

Anastrozole has fewer side effects

Data from the landmark study at 68 months also showed that anastrozole had fewer side effects than tamoxifen, and study authors recommended that patients currently taking tamoxifen discuss with their doctors the possibility of switching to anastrozole.

Tamoxifen, which has been used to treat breast cancer for more than 30 years, has long been touted as the best drug to help prevent recurrence. However, it has been associated with life-threatening side effects in some women.

"The side effects of tamoxifen are not predictable and include increased risk of blood clots, strokes, vaginal bleeding and cancer of the uterus," Buzdar says. "In this study, four times more women in the tamoxifen group had hysterectomies compared to women in the anastrozole group, which is a reflection of the effect of tamoxifen on the uterus."

The study found that women taking anastrozole experienced more fractures and joint pain than those receiving tamoxifen, but study authors state that those side effects were believed to be more manageable than the side effects from tamoxifen.

Results mark major milestone for landmark study

The results represent the mature findings of the largest international breast cancer trial in the world, the five-year trial known by its acronym ATAC (Arimidex, Tamoxifen, Alone or in Combination). ATAC enrolled 9,366 women treated for breast cancer from 380 cancer centers in 21 countries, beginning in 1996. Three years into the study, combining the two drugs was not found to be effective, so only a comparison of the two drugs remained.

The five-year results of the study found that compared to tamoxifen, anastrozole:

• Prolonged disease-free survival by 13%
• Prolonged time to recurrence by 17%
• Reduced cancer spread to other parts of the body by 14%
• Reduced the risk of a new cancer to the other breast by 42%

There was no significant difference in overall survival rates, but patients treated with anastrozole had 13% fewer deaths related to breast cancer. These findings, and anastrozole's reductions in recurrence, suggest that a decrease in deaths will eventually be seen.

Treatment in the study has been completed by 92% of patients, Buzdar says, and patients will be monitored for at least 10 years.

Drugs fight breast cancer tumor cells differently

As with tamoxifen, the study recommends that anastrozole be taken for five years following surgery to remove breast cancer. According to experts, the first five years after breast cancer surgery is when a woman is at greatest risk of the cancer returning.

ATAC compared standard hormonal therapy (tamoxifen) to anastrozole, an aromatase inhibitor that blocks an enzyme that converts androgens (male hormones) into estrogens in postmenopausal women.

Tamoxifen is a selective estrogen receptor modulator (SERM) that works by competing with estrogen to bind to estrogen receptors on tumor cells.