Toxicity of Aromatase Inhibitors May Explain Lack of Overall Survival Benefit

Taken from www.knowbreastcancer.org

August 23, 2011
In a review published in this month's Journal of the National Cancer Institute, Dr. Eitan Amir and colleagues examined whether the relative toxicity of Aromatase Inhibitors (AIs) versus tamoxifen might explain the lack of overall survival benefit associated with AIs in breast cancer patients.  Aromatase Inhibitors (AIs), a class of endocrine therapy drugs used to treat postmenopausal breast cancer patients, are associated with improvements in disease-free survival but not overall survival.  Amir and colleagues at Princess Margaret Hospital in Toronto conducted a systematic review of randomized controlled trials that compared aromatase inhibitors and tamoxifen as primary adjuvant endocrine therapy in postmenopausal women.  Their meta-analysis consisted of seven trials enrolling 30,023 patients.
The researchers found that compared to tamoxifen, longer use of AIs was associated with an increased odds of cardiovascular disease and bone fractures, but lower rates of blood clots and endometrial cancer.  There was no difference in the risk of second cancers or stroke in patients receiving tamoxifen vs. AIs.  Furthermore, use of AIs for 2-3 years after initial treatment with tamoxifen was associated with a lower risk of death from other causes (without breast cancer recurrence) compared to the use of tamoxifen or AIs alone for 5 years.  The authors conclude that "The cumulative toxicity of aromatase inhibitors when used as up–front treatment may explain the lack of overall survival benefit despite improvements in disease–free survival. Switching from tamoxifen to aromatase inhibitors reduces this toxicity and is likely the best balance between efficacy and toxicity." 
In an accompanying editorial, Dr. Nancy Davidson and colleagues write that physicians should "choose initial endocrine therapy for the individual patient with careful attention to the risk of breast cancer recurrence, the risk of toxicity, and comorbidities."  Since this meta-analysis and another suggest that switching strategies may be effective, the authors conclude that "we should not ditch the switch.”