Switching to Aromatase Inhibitors After Tamoxifen Improves Survival in Early Breast Cancer

Zosia Chustecka

February 12, 2007

February 12, 2007 — For breast cancer patients who have taken tamoxifen for 2 to 3 years, switching to an aromatase inhibitor (AI) is better than staying on tamoxifen, as the switch significantly improves survival. So concludes a pooled analysis of 2 prospective trials in a paper published online February 12 in Cancer.

Several trials have already suggested a superiority of aromatase inhibitors over tamoxifen in the adjuvant treatment of early breast cancer, but not all studies have shown a mortality benefit, say the authors, led by Francesco Boccardo, MD, from the National Cancer Research Institute and University of Genoa, Italy. By pooling the results of 2 trials together, they found that women who switched to an AI had lower mortality from all causes as well as lower mortality related to breast cancer when compared with women who stayed on tamoxifen, and there appeared to be no increase in death from other causes.

"This pooled analysis provides solid evidence that switching to an aromatase inhibitor following a few years of tamoxifen treatment implies a mortality benefit over continued tamoxifen and that the benefit on breast cancer–related mortality is mainly due to the effect of switching," the authors conclude.

These new data reinforce the indication of early switching to an AI in women currently receiving adjuvant treatment with tamoxifen, they add.

Other evidence of mortality benefits that also supports this switching approach has come from the Intergroup Exemastane Study and the anastrozole ARNO 95 study and from a meta-analysis of 3 trials with anastrozole (Jonat W et al. Lancet Oncol 2006;7:991-996).

Pooled Analysis of Data Was Preplanned


Dr. Boccardo explains that his group has been developing the "switching approach" since 1992 and previously conducted 2 trials in which women who were taking tamoxifen were switched over to an AI. In the earlier trial (GROCTA 4 B), the switch was to aminogluthimide, an early AI product that is not used anymore, while the later trial (ITA) allowed a switch to anastrozole ( Arimidex
, AstraZeneca). Otherwise, the trials were similar in design and in selection criteria. The current pooled analysis was prospectively planned at the time that the ITA trial was designed, the researchers note.

Together, the 2 trials involved 828 postmenopausal women, mostly with estrogen-receptor (ER)-positive and node-positive breast cancer. All the women took tamoxifen for an average of 3 years, after which some were randomized to switch to an AI while the others continued on tamoxifen. The overall median follow-up was 78 months (range, 6 – 141 months), but the women in the earlier GROCTA trial had been followed for longer (median 104 months) than those in the ITA trial (median 64 months).

When compared with the women who stayed on tamoxifen, the women who switched to an AI had significantly lower all-cause mortality, with a hazard ratio (HR) of 0.61 (95% CI, 0.42 – 0.88; P
= .007), and significantly lower breast cancer–related mortality (HR, 0.61; 95% CI, 0.39 – 0.94; P
= .025). Both of these mortality benefits were still statistically significant even after multivariate analysis by patient age, tumor size and grade, nodal status, and prior local and/or systemic treatment.

Pooled Analysis of the GROCTA 4B and ITA trials
Outcome
Staying on Tamoxifen
(n=415)
Switching to AI
(n=413)
Death from any cause
74
48
Breast cancer relapse
51
33
Second primary tumor
3
6
Stroke
4
1
Cardiovascular event
12
5
Other causes
2
1
Missing information
2
2

There was no significant difference between the 2 groups in mortality unrelated to breast cancer. However, these numbers were small and are less likely to be reliable, the researchers comment, adding that the median follow-up was different in the 2 trials, which may be crucial. Despite these cautions, they highlight the finding that women who switched to an AI had fewer deaths from stroke and from cardiovascular causes, including lethal cardiac ischemic events. "It should not be underestimated that no increase in cardiac ischemic events was reported in any of the other adjuvant trials with aromatase inhibitors reported so far," they add.

Cancer. Published online February 12, 2007.

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