SAN ANTONIO -- Switching postmenopausal breast cancer patients to an aromatase inhibitor following 2-3 years of adjuvant tamoxifen results in markedly better disease-free survival than the traditional 5 full years of tamoxifen, according to three major randomized trials presented at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.
Raimund Jakesz, M.D., recommended that breast cancer patients who fit the profile of participants in two European clinical trials he reported on at the conference be routinely switched to 3 years of anastrozole (Arimidex) after 2 years of tamoxifen.
He reported on more than 3,100 breast cancer patients in the AstraZeneca-sponsored Austrian Breast and Colo rectal Cancer Study Group Trial 8 and the German Adjuvant Breast Cancer Group ARNO 95 study who were randomized to 5 years of adjuvant tamoxifen or to 2 years of tamoxifen followed by 3 years of anastrozole.
The 3-year rate of freedom from locoregional recurrence, distant metastasis, and contralateral breast cancer was 95.8% in the tamoxifen/anastrozole group, compared with 92.7% in the tamoxifen arm. The likelihood of survival free of distant recurrence was 39% greater with tamoxifen followed by anastrozole, said Dr. Jakesz, professor of surgery at the University of Vienna.
All participants in the two randomized trials were postmenopausal, had hormone receptor-positive disease, and underwent breast-conserving therapy. One-quarter were node positive. None received chemotherapy. Forty percent were under 60 years old. Most patients had small, well-differentiated tumors.
In a separate presentation, Charles Coombes, M.D., presented an update on the Intergroup Exemestane Study (IES), in which 4,740 postmenopausal breast cancer patients were randomized to 5 years of adjuvant tamoxifen or switched to exemestane (Aromasin) after 2-3 years. At a median 37 months of follow-up, local or distant recurrence had developed in 264 women treated with tamoxifen and 193 switched to the aromatase inhibitor. That translated into a 27% increase in disease-free survival in patients who switched.
Twelve cases of contralateral breast cancer occurred in the tamoxifen/exemestane group, compared with 26 in those treated with tamoxifen alone.
In addition, there have been significantly fewer new primary cancers at sites other than the breast with exemestane: 46, compared with 59 in the tamoxifen-only arm. There have been, for example, 6 cases of lung cancer in the tamoxifen/exemestane group, compared with 13 in the tamoxifen group, and 2 cases of melanoma, compared with 5 cases in the tamoxifen-only arm. On the other hand, 20 acute MIs have occurred in patients switched to the aromatase inhibitor, versus just 8 MIs in the tamoxifen-only group, said Dr. Coombes, director of the Cancer Research UK Laboratories at Imperial College, London.
A midcourse switch from tamoxifen to an aromatase inhibitor makes a lot of sense, Hope S. Rugo, M.D., said at a satellite symposium held in conjunction with the San Antonio conference. Tamoxifen is of proven benefit in preventing recurrent breast cancer. It's a good drug with favorable ancillary effects on bone mineral density and the cardiovascular risk profile. But tamoxifen resistance can occur as early as 12-18 months after starting therapy.
Endometrial cancer and thromboembolism--side effects associated with tamoxifen--become more likely with longer treatment duration. Stopping tamoxifen early might prevent adverse events while providing protection against the increased fracture risk associated with 5 years of anastrozole in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, said Dr. Rugo, director of the breast oncology clinical trials program at the University of California, San Francisco, Comprehensive Cancer Center.
BY BRUCE JANCIN
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