Aromatase inhibitors superior to tamoxifen in reducing ER positive breast cancer recurrence

1. In this meta-analysis of randomized controlled trials, estrogen receptor (ER) positive breast cancer recurrence rate was lower with an aromatase inhibitor over tamoxifen during years 0-1 and 2-4, but not thereafter.

2. Overall 10-year breast cancer mortality favored aromatase inhibitors. The incidence of endometrial cancer was also reduced with aromatase inhibitors compared to tamoxifen.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Breast cancer is a leading cause of cancer deaths for women in developed countries. It is further classified into subtypes based on hormonal receptor positivity for treatment and prognostic purposes. In this meta-analysis of randomized controlled trials, the investigators compared aromatase inhibitors to tamoxifen in preventing recurrence and death for patients with ER positive breast cancer. Results showed that aromatase inhibitors were superior to tamoxifen during the earlier years (0-1 and 2-4) of follow-up in reducing recurrence (rate ratio = 0.85), but not thereafter. The 10-year overall mortality was found to be lower with aromatase inhibitors than with tamoxifen. The incidence of endometrial cancer was also lower with aromatase inhibitors compared to tamoxifen. The study was strengthened by the large number of patients (31 920) included in the final analyses. A potential weakness is that the study did not factor into compliance.

The study was funded by Cancer Research UK, Medical Research Council.

Click to read the study in The Lancet

Relevant Reading: Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials

In-Depth [meta-analysis]: This meta-analysis included data from 31920 women in 9 trials. Eligible trials began in 2005 and randomized post-menopausal women to receive either an aromatase inhibitor or tamoxifen during various time frames in treatment. The primary outcomes were any recurrence of breast cancer, breast cancer mortality, and all-cause mortality.

In comparing 5 years of aromatase inhibitor versus 5 years of tamoxifen (comparison A, 2 trials, n = 9885), there were fewer recurrences with aromatase inhibitors (p<0.00001), with significant reductions during years 0-1 post-op (rate-ratio, RR, 0.64, 95% CI 0.52-0.78), and during years 2-4 (RR 0.80, 95% CI 0.68 – 0.93). There was no significant effect after the scheduled treatment period. The 10-year recurrence risk was lower with aromatase inhibitors (difference 3.6%, 95% CI, 1.7 – 5.4). 10-year breast cancer mortality was lower with aromatase inhibitors (RR 0.85, 95% CI 0.75 – 0.96, 2p=0.009).

In comparing 5 years of aromatase inhibitors versus 2-3 years of tamoxifen then an aromatase inhibitor to year 5 (comparison B, 3 trials, n = 12779), there was a smaller but statistically significant reduction in total recurrence with aromatase inhibitors compared to tamoxifen-aromatase inhibitors (2p = 0.045). There was no significant reductions in breast cancer mortality (2p = 0.11) or all-cause mortality.

In comparing 2-3 years of tamoxifen then an aromatase inhibitor to year 5 versus 5 years of tamoxifen (comparison C, 6 trials, n = 11798), allocation to an aromatase inhibitor reduced the recurrence rate during years 2-4 (RR 0.56, 95% CI 0.46 – 0.67, p<0.0001). Breast cancer mortality was reduced (RR 0.84, 95% CI 0.77 – 0.97, 2p=0.015), as was all-cause mortality (2p=0.0002).

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