Postmenopausal women with breast CA: exemestane after tamoxifen increases survival.(Gynecology)

Switching to exemestane therapy after 2-3 years of tamoxifen treatment improves disease-free survival in postmenopausal women with breast cancer, according to Dr. R. Charles Coombes and his associates in the Intergroup Exemestane Study, a large randomized trial.

The standard approach of giving tamoxifen alone for 5 years after resection of estrogen-receptor-positive breast cancer now appears to be "suboptimal." Physicians should consider offering tamoxifen for 2-3 years and the aromatase inhibitor exemestane for the balance of the 5-year period of adjuvant endocrine therapy, said Dr. Coombes of the department of cancer medicine at Imperial College, London, and his associates.

The researchers don't yet know the molecular mechanism that makes this sequential regimen more effective. It is possible that, over time, tamoxifen's antagonist properties decline and sensitivity to estradiol increases. Aromatase inhibitors and inactivators are known to decrease estradiol levels.

In theory, switching to exemestane should counter the resistance that often develops to tamoxifen, sometimes as early as 12-18 months after starting treatment. It should also avert the serious side effects, including thromboembolism and uterine cancer, that can develop with prolonged tamoxifen therapy, they said.

The study, which involved 4,742 women treated in 37 countries, was halted in December and its results announced early after an interim analysis of the data revealed that switching to exemestane yielded an absolute disease-free survival benefit of nearly 5%, compared with continuing tamoxifen. Whether such a switch yields a benefit in overall survival cannot be determined yet because "the observed number of deaths over the relatively short follow-up period precludes the detection of a statistically significant difference in overall survival," the researchers noted (New Engl. J. Med. 350[11]:1081-92, 2004).

The study subjects had undergone resection of primary unilateral breast carcinoma, as well as postoperative radiotherapy or chemotherapy as indicated. All had received adjuvant tamoxifen for 2-3 years. A total of 2,380 were randomly assigned to continue on oral tamoxifen (20 mg or 30 mg), and 2,362 were assigned to switch to oral exemestane (25 ...