Anastrozole

SAN ANTONIO -- Five years of the aromatase inhibitor anastrozole has now replaced tamoxifen as the endocrine therapy of choice for primary adjuvant therapy of women with hormone receptor-positive early-stage breast cancer, Anthony Howell, M.D., said at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

He presented the updated results of the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial, which at a mean follow-up of 68 months continues to show superior efficacy for anastrozole (Arimidex), as has consistently been the case since the first year of follow-up.

ATAC is an AstraZeneca-sponsored, randomized, double-blind trial for which data are available on 9,366 post-menopausal women with early-stage breast cancer treated at 381 sites in 21 countries. Participants were randomized to 5 years of tamoxifen, anastrozole, or both, although the combination treatment arm was halted early because of clearly inferior results, explained Dr. Howell of the University of Manchester, England.

At 68 months, 16% of hormone receptor-positive patients in the anastrozole arm had died or developed recurrent breast cancer, compared with 19% of tamoxifen-treated patients. The anastrozole group also had significant relative advantages of 26% in time to local recurrence, 16% in time to distant recurrence, and a 53% lower rate of contralateral breast cancer. Among hormone receptor-positive patients, there were 152 breast cancer deaths in the anastrozole arm and 172 in the tamoxifen arm, a trend that didn't reach significance but may do so with several more years of follow-up, he said.

The incidences of endometrial cancer, thromboembolic events, and ischemic stroke were significantly lower in the anastrozole group. However, the rates of osteoporosis, fractures, and arthralgias were significantly greater with anastrozole than with tamoxifen.

Despite Dr. Howell's call for anastrozole to be considered the agent of choice for first-line initial endocrine therapy, many oncologists indicated that they--and large numbers of their patients--remain unwilling to do so routinely for now.

That reservation is reflected in a recent American Society of Clinical Oncology technology assessment, which advised that adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer "should include an aromatase inhibitor in order to lower the risk of tumor recurrence," without specifying whether the agent should be used as initial therapy or after tamoxifen. The ASCO report cited as reservations the still limited data regarding the late consequences of aromatase inhibitor therapy and how best to utilize these agents.

ASCO took a conservative stance--and appropriately so, Hope S. Rugo, M.D., said at a satellite symposium sponsored by Merck and Co.

In her own practice, she favors using an aromatase inhibitor from the beginning in women at increased risk for osteoporosis or thromboembolism, and in those with higher-risk breast cancer as defined by a human epidermal growth factor receptor 2 (HER2)-positive and / or estrogen receptor-positive / progesterone receptor-negative (ER + / PgR-) tumor.

"For the average woman, though. I do tend to think that maybe a couple of years of tamoxifen isn't a bad thing. I discuss the data with each patient. And I have to say, many patients are still very enthusiastic about taking tamoxifen. It's kind of gone in reverse: Whereas before nobody wanted to take tamoxifen and everybody thought it was an evil drug, now many people are saying, 'No, I want to take tamoxifen; I'm worried about the long-term side effects of the aromatase inhibitors,'" said Dr. Rugo, codirector of the breast oncology clinical trials program at the University of California, San Francisco, Comprehensive Cancer Center.

BY BRUCE JANCIN

Denver Bureau

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