▸ Patient populations. Patients who were switched to aromatase inhibitors after they did not recur while on tamoxifen are not the same as patients who were randomized to a sequence of tamoxifen followed by an aromatase inhibitor. “Switching-study patient populations are by default enriched with patients who respond well to endocrine therapy by excluding patients who have had an early recurrence despite tamoxifen treatment,” the panel wrote.
▸ No direct comparisons. Until the Breast International Group-98 trial publishes mature data comparing 5 years of letrozole therapy with sequence therapy, no data are available from trials comparing a sequential strategy with monotherapy. For now, the panel found that the best researchers can do is to construct models based on existing data.
▸ Duration of therapy. Although the optimal duration of tamoxifen therapy is 5 years, and 5 years has been adopted as the standard for endocrine therapy, the optimal duration of aromatase inhibition is not known. “It is possible that shorter or longer periods of adjuvant therapy may be suitable for different patients, depending upon their specific disease characteristics,” the panel wrote.
▸ Cardiac, stroke, and endometrial cancer risk. Data on patients with preexisting coronary heart disease are not available for tamoxifen or aromatase inhibitors, according to the panel. Although there is no evidence that these patients should be excluded from treatment with aromatase inhibitors, this needs to be studied.
Some studies have associated tamoxifen with increased risk of stroke, endometrial cancer, and possibly deep venous thrombosis. The panel found that these risks are not predictable in individual patients, however. It also suggested that stroke risk may be reduced with one or more aromatase inhibitors, but more evidence is needed.