Meta-analysis Finds Aromatase Inhibitors Decrease Rates of Cancer Recurrence and Death Compared with Tamoxifen

DECEMBER 12, 2008
Christin Melton
Multiple studies presented at the 2008 CTRC-AACR San Antonio Breast Cancer Symposium report encouraging findings on the role of aromatase inhibitors (AIs) in treating postmenopausal women with early-stage estrogen receptor-positive breast cancer. James Ingle, MD, director of the Breast Cancer Specialized Program of Research Excellence at the Mayo Clinic Cancer Center, Rochester, MN, presented results of a meta-analysis of several prospective trials that investigated aromatase inhibitors as adjuvant monotherapy or in sequence with tamoxifen.

Dr. Ingle’s group divided the patients into two cohorts. Cohort one (n = 9856) comprised patients who underwent five years of adjuvant therapy with either tamoxifen or an AI (anastrozole [Arimidex], exemestane [Aromasin], or letrozole [Femara]). Cohort two (n = 9015) included patients who received adjuvant therapy with two to three years of tamoxifen followed by two to three years of an AI (total treatment span = 5 y).

In cohort one, researchers found that patients who received tamoxifen monotherapy for five years had a 12.6% rate of cancer recurrence versus 9.6% for patients who received AIs (SE, 0.7). The greatest declines in cancer recurrence associated with AI use were seen in the rates of isolated local recurrence and contralateral disease. Between years three and five, the annual disparity between the two regimens as to the number of women who developed cancer recurrence diminished somewhat, but at eight years’ follow-up, there were still more women in the tamoxifen group who suffered recurrence than in the AI group (19.2% vs 15.3%, respectively).

At the five-year point, women who received adjuvant monotherapy with an AI also had a lower rate of mortality due to breast cancer compared with women who took tamoxifen (4.8% vs 5.9%). The mortality rate at eight years was 10.5% for patients who received tamoxifen versus 10.0% for those who took an AI. Dr. Ingle said that the difference in mortality rates between the regimens was not significant.

In analyzing data for patients in cohort two, investigators found that patients who received at least two years of therapy with an AI after two to three years of tamoxifen were less likely to redevelop cancer than those who received five years of tamoxifen monotherapy (5.0% vs 8.1%, respectively). The rates of recurrence six years after the point when some patients switched to an AI regimen still showed a higher rate of recurrence for those in the tamoxifen group, compared with the sequential group (16.1% vs 12.6%, respectively).

Dr. Ingle noted that there were significantly greater reductions in the rate of recurrence in the three years that women were undergoing therapy with an AI than in the years after therapy was discontinued. He said this finding “raises the question of the value of AI therapy beyond five years.”

Dr. Ingle emphasized that although there was less divergence in the rates of recurrence between the regimens over time, “You don’t lose the benefit that is gained.” He said the results showed that “AIs are still better [than tamoxifen]…AIs are not doing worse after three years. [They’re] just not doing ‘as better.’”

Women in cohort two who received tamoxifen followed by an AI had a significantly lower rate of death due to breast cancer compared with women who only took tamoxifen (1.4% vs 2.4%, respectively, at three years; and 6.3% vs 8.0%, respectively, at eight years). Investigators did not observe any significant difference between the two regimens in the number of non–breast cancer deaths or overall deaths, which Dr. Ingle said was “reassuring” in regard to the overall safety of AIs. The researchers concluded that additional follow-up was needed to determine the “relative efficacy” of tamoxifen compared with AIs.

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