Aromatase inhibitors edge out tamoxifen for preventing recurrences

December 11, 2008

Aromatase inhibitors were associated with greater reductions in the risk of breast cancer recurrence in comparison with tamoxifen, according to a meta-analysis involving nearly 20,000 hormone receptor-positive early breast cancer patients.

SAN ANTONIO-Aromatase inhibitors were associated with greater reductions in the risk of breast cancer recurrence in comparison with tamoxifen, according to a meta-analysis involving nearly 20,000 hormone receptor-positive early breast cancer patients.

James Ingle, MD, and his team at the Mayo Clinic in Rochester, Minn., concluded that for patients receiving endocrine monotherapy, AIs reduced the risk of recurrence by 23% over tamoxifen. For patients who switch to AIs after two to three years of tamoxifen, risk is reduced by 29% over tamoxifen continuation.

The study was based on outcomes data submitted to the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) in Oxford, UK, based on six major trials that began by 2000. Patients were assessed according to the manner in which they received the drugs.

Cohort 1 included 9,856 patients receiving endocrine monotherapy. After five years, use of AIs was associated with a breast cancer recurrence rate of 15.3%, compared with a rate of 19.2% with tamoxifen (P <.00001).

"Compared with tamoxifen, the use of AIs as monotherapy was associated with an absolute gain in disease-free survival of 2.9% at five years and 3.9% at eight years, which was highly significant," said Dr. Ingle, who is director of the breast cancer program at the Mayo Clinic.

The disease-free–survival difference was more pronounced for isolated local recurrence and contralateral disease than for distant disease recurrence. For overall survival in the monotherapy cohort, AIs yielded an absolute gain of 1.1% at five years and 0.5% at eight years, but this was not statistically significant.

Cohort 2 included 9,015 patients who received AIs after two to three years of tamoxifen therapy in a so-called switching strategy. Breast cancer recurred in 12.6% of patients receiving AIs compared with 16.1% receiving tamoxifen, for an absolute disease-free survival gain of 3.1% at three years and 3.5% at five years, also highly significant (P <.00001), Dr. Ingle reported.

In the switch cohort, breast cancer mortality was significantly reduced with AIs, which were associated with an absolute gain in survival of 0.7% at three years and 1.6% at six years from treatment divergence. Death from any cause was also significantly reduced with AIs.

For the monotherapy cohort, proportional reductions were similar in the first two and last three years of treatment, with further reductions beyond five years that were not statistically significant. For the switch cohort, significantly greater reductions were observed during the first three years, while patients were still on treatment, than beyond.

The findings draw attention to the potential value of longer AI-based therapy, Dr. Ingle said. In fact, duration of AI treatment still needs to be determined.

"There is a change when patients go off therapy, [and] AIs are still better-only at this point they are 8% better than tamoxifen, and not 40% better," he said.

There was no indication that AIs were associated with an increase in mortality, which is reassuring regarding their overall safety profile, he added.

"Naturally, clinicians need to balance the efficacy gain with tolerance of the individual patient," he said.