Aromatase Inhibitors (AIs) As Adjuvant Therapy for Postmenopausal Women With Hormone-Receptor Breast Cancer: The End of Tamoxifen?
By Medscape Ob/Gyn & Women's Health board member
Andrew M. Kaunitz, MD
The standard adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancers has been tamoxifen. However, use of this selective estrogen receptor modulator is associated with an elevated risk of venous thromboembolism, and, in women with a uterus, uterine bleeding and endometrial neoplasia. Aromatase inhibitors (currently marketed AIs include anastrozole, letrozole, and exemestane), which block the synthesis of estrogen metabolized from adrenal androgens, have emerged as promising agents for the treatment of postmenopausal breast cancer. (For reviews, see Winer and colleagues, Sokolowicz and Gradishar.) Several large randomized trials of AIs in postmenopausal women with hormone receptor-positive breast cancers published in late 2003 and 2004 suggest that AIs should now constitute primary endocrine adjuvant therapy.[212,213,214,215]
Compared with tamoxifen, AIs prolong disease-free survival, reduce distant metastatic disease, and minimize the incidence of contralateral breast cancers. Compared with tamoxifen, AIs are better tolerated (fewer hot flashes, less vaginal bleeding) and cause fewer vascular events and less endometrial disease. Nonetheless, because of the profound reduction in endogenous estrogen levels caused by AIs in postmenopausal women, use of these important medications results in arthralgia in some women and reduced BMD. In a 5-year randomized trial comparing tamoxifen and anastrozole, the overall incidence of fractures was higher with the AI. However, hip fractures were uncommon, and their incidence was similar in the 2 treatment groups.
On the basis of these and other studies, ASCO recently updated its recommendations for postmenopausal women with hormone receptor-positive breast cancer. (See Medscape Medical News CME story.) Specifically, ASCO now recommends that adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer should include an AI in order to lower the risk of tumor recurrence. The organization indicates that AIs either be used as initial endocrine adjuvant therapy or that tamoxifen be used for several years, with subsequent AI therapy. ASCO's recommendations also acknowledge that the optimal duration of AI therapy is still unknown and that much remains to be learned regarding late consequences of AI therapy, most notably osteoporotic fractures.
Women's health clinicians should anticipate seeing more breast cancer survivors using AIs and fewer using tamoxifen. The arthralgias reported by some women using AIs may represent phenomena similar to symptoms attributed to gonadotropin-releasing hormone analogues such as leuprolide. Because the most serious adverse events associated with AI use are loss of BMD and fractures, assessment of fracture risk, including monitoring of BMD when appropriate, would seem prudent for women undergoing long-term AI therapy. When risk factors and/or findings of BMD assessments warrant, concomitant use of bisphosphonates also represents an important component of the care of women receiving AIs.
Two out of 3 breast cancers are hormone receptor positive. The emergence of AIs as the preferred adjuvant endocrine therapy for hormone receptor-positive breast cancer in menopausal women will improve the quality of life and clinical outcomes for this large population of women. Because of the endometrial and vascular risks associated with tamoxifen, women's health clinicians have been reluctant to use it for chemoprophylaxis of breast cancer in high-risk women. Our rapidly expanding knowledge regarding AIs, however, may lead to a new standard of prophylactic care for menopausal women at high risk for breast cancer.
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Cite this: December 2004: The Year in Review -- Ob/Gyn & Women's Health - Medscape - Jan 18, 2005.