A large meta-analysis has indicated that adjuvant treatment with aromatase inhibitors (AIs) provides improved outcomes in terms of recurrences and mortality compared with tamoxifen (Nolvadex®) in the treatment of hormone-positive, early breast cancer among postmenopausal women. These results were recently presented at the 2008 annual San Antonio Breast Cancer Symposium in San Antonio, Texas.

Several large trials comparing AIs to tamoxifen have established the efficacy and safety of AIs for the treatment of hormone-positive breast cancers among postmenopausal women. Follow-up of these trials continues to evaluate long-term outcomes and side effects of both classes of agents in order to individualize therapy for this group of patients. To further understand overall effects of AIs in breast cancer, researchers affiliated with the Aromatase Inhibitors Overview Group conducted a meta-analysis including results from the following six randomized trials, which compared AIs with tamoxifen as adjuvant therapy in postmenopausal women with hormone-positive breast cancer:

• Arimidex, Tamoxifen, Alone or in Combination (ATAC)
• Breast International Group (BIG) 1-98/International Breast Cancer Study Group (IBCSG) 18-98
• Austrian Breast and Colorectal Cancer Study Group (ABCSG)
• German Austrian Breast Cancer Group (GABG)/Arimidex-Nolvadex (ARNO)
• Intergroup Exemestane Study (IES)/BIG 2-97
• Italian Tamoxifen Anastrozole (ITA)

The trials in this analysis had been initiated by the year 2000 and included both monotherapy trials, in which AIs were compared to tamoxifen as monotherapy for five years, and switch trials, in which five years of tamoxifen was compared to two to three years of tamoxifen followed by two years of an AI.  The aromatase inhibitors in the trials included either Femara® (letrozole), Arimidex® (anastrozole), or Aromasin® (exemestane). Monotherapy trials and switch trials were evaluated as separate cohorts.  Endpoints of the meta-analysis included relative recurrence and survival rates.

Among the monotherapy trials, the following results were reported:

• Recurrence rates at five and eight years were 9.6% and 15.3% on the AI arm compared with 12.6% and 19.2% on the tamoxifen arm (P<0.00001).
• Survival differences did not reach statistical significance between the two treatment arms

Among the switch trials, the following results were reported:

• Recurrence rates at three and six years were 5.0% and 12.6% on the AI arm compared with 8.1% and 16.1% on the tamoxifen arm (P<0.00001).
• Breast cancer mortality at six years was 6.3% on the AI arm compared with 8.0% on the tamoxifen arm (P=0.02).
• Six-year risk of death from any cause was 10.8% on the AI arm compared with 13.0% on the tamoxifen arm (P=0.004).

The researchers stated that results from this meta-analysis provide clear evidence that AIs significantly reduce recurrences in early, hormone-positive breast cancer compared with tamoxifen. As well, it appears that switching to AIs after two to three years of therapy with tamoxifen compared with five years of monotherapy with tamoxifen improved both breast cancer-specific and overall survival among these patients. However, the mean survival follow-up in this meta-analysis is only 3.9 years; longer follow-up may provide different results for this important endpoint.

Reference: Ingle J, et al. Aromatase inhibitors versus tamoxifen as adjuvant therapy for postmenopausal women with estrogen receptor positive breast cancer: meta-analysis of randomized trials of monotherapy and switching strategies. San Antonio Breast Cancer Symposium. December 10-14, 2008. Abstract 12.