Latest News on Adjuvant Therapies for Breast Cancer Survivors

Are aromatase inhibitors safe and effective as adjuvant therapy for postmenopausal women with estrogen receptor-positive breast cancer?

Are aromatase inhibitors safe and effective as adjuvant therapy for postmenopausal women with estrogen receptor-positive breast cancer?

More than 1 million women throughout the world have breast cancer, and about 400,000 of them die each year.1 Advances in therapy continue, although some treatments seem to have withstood the test of time. For more than 20 years, tamoxifen has been used as adjuvant therapy for hormone receptor-positive breast cancer in postmenopausal women.

But tamoxifen, though still a highly effective treatment, is not perfect. Its partial estrogenic effects increase the risk of thromboembolism as well as endometrial cancer. Furthermore, even though tamoxifen therapy is known to be beneficial after 5 years, risks and drug resistance preclude longer use. Adjuvant therapy continued beyond 5 years might improve survival. Is there a more effective and less toxic alternative?

Aromatase inhibitors are increasingly used as adjuvant therapy in postmenopausal women with endocrine-responsive breast cancer. These drugs suppress estrogen levels by inhibiting aromatase, an enzyme that synthesizes estrogen from androgen substrates in the body. Moreover, unlike tamoxifen, aromatase inhibitors (anastrozole, letrozole, and exemestane) do not possess partial estrogen agonist activity and thus should pose less risk of thromboembolic events and endometrial cancer.

Jakesz and coinvestigators1 compared tamoxifen alone and in combination with anastrozole in the treatment of early hormone-responsive breast cancer in postmenopausal women. After patients had completed 2 years of adjuvant tamoxifen therapy, 1618 were switched to anastrozole and 1606 continued to receive tamoxifen. After 28 months of follow-up, there was a 40% decrease in the risk of an event (local or distant metastases or contralateral breast cancer) in the anastrozole group compared with the tamoxifen group. In addition, patients treated with anastrozole had fewer thrombotic events-but more fractures.

Two large trials currently under way are head-to-head comparisons of tamoxifen followed by an aromatase inhibitor and an aromatase inhibitor alone as primary postmenopausal breast cancer adjuvant treatment. The results are expected in 2008.

For now, remainvigilant about the risks of thromboembolic disease and endometrial cancer in patients who are receiving tamoxifen therapy. Encourage patients who volunteer for prospective studies on future adjuvant therapies as well as those who are currently taking an aromatase inhibitor for postmenopausal breast cancer that these agents look promising.

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1.

Jakesz R, Jonat W, Gnant M, et al. Switching of postmenopausal women with endocrine-responsive earlybreast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO95 trial. Lancet. 2005;366:455-462.