Clinical and Economic Benefits of Aromatase Inhibitor Therapy in Early-stage Breast Cancer

Stefan Glück; Fariborz Gorouhi

Disclosures

Am J Health Syst Pharm. 2011;68(18):1699-1706. 

In This Article

Abstract and Introduction

Abstract

Purpose. The clinical and economic benefits of aromatase inhibitor (AI) therapy in early-stage breast cancer are reviewed.
Summary. AI therapy has become a standard of care for the treatment of most postmenopausal women with early-stage breast cancer, as it significantly reduces the risk of disease recurrence and death. Using the currently accepted gold standard for clinical efficacy—improvement in disease-free survival rather than overall survival—exemestane, anastrozole, or letrozole as monotherapy or in sequence with tamoxifen has been found to be superior to tamoxifen monotherapy. Emerging data have demonstrated potential overall survival advantages for AIs subsequent to and directly related to distant recurrence. Of the nonsteroidal AIs, letrozole appears to have the efficacy advantage by demonstrating an early effect on distant recurrence and, subsequently, a potentially significant overall survival benefit, though results of a prospective head-to-head trial of anastrozole and letrozole are not yet available. When the economic burden to society is considered, it appears that all AIs are similarly beneficial on the basis of disease recurrence. However, preliminary analyses indicate that the survival benefit appears to be greater with letrozole than with anastrozole. Thus, considering potential survival benefits and cost-effectiveness, letrozole may be preferable to anastrozole in the early adjuvant setting.
Conclusion. AI therapy has become a standard of care for the treatment of most postmenopausal women with early-stage breast cancer. Emerging data have demonstrated potential overall survival advantages for AIs subsequent to and directly related to distant recurrence. When the economic burden to society is considered, it appears that all AIs are similarly beneficial on the basis of disease recurrence.

Introduction

Breast cancer is the most frequently diagnosed malignancy in women, with over 1.4 million new cases in 2008.[1] While significant treatment advances have been made, all patients face the risk of disease recurrence, which is the main cause of death from breast cancer.[2] Early detection and improved treatment options have reduced the rate of death due to breast cancer, decreasing from 0.4% (1990–95) to −1.9% (1998–2006) in the United States alone.[3] However, it is estimated that 458,400 women died of the disease in 2008.[1]

Consensus guidelines routinely recommend inclusion of adjuvant endocrine therapy for postmenopausal women with early-stage invasive breast cancer whose tumors express the estrogen receptor (ER).[4][6] The selective ER modulator tamoxifen competes with estrogen for binding to the ER (Figure 1). Tamoxifen has been shown to reduce the annual breast cancer mortality rate compared with no endocrine therapy by 31% regardless of chemotherapy use, patient age, progesterone-receptor status, or other tumor characteristics.[7] While tamoxifen remains appropriate for some patients, consensus guidelines typically recommend the inclusion of aromatase inhibitor (AI) therapy,[4,5,8] particularly for patients at high risk for relapse.[5] Nonsteroidal (letrozole and anastrozole) and steroidal (exemestane) AIs inhibit the ability of aromatase to convert androgens to estrogens (Figure 1). The recommendations for inclusion of AI therapy are based on the results of large randomized trials that evaluated the benefits of AI therapy, particularly with regard to disease-free survival, when administered as monotherapy or in sequence with tamoxifen.[9][13]

Figure 1.

Mechanism of action of aromatase inhibitors and tamoxifen. Reprinted from Smith IE, Dowsett M. Aromatase inhibitors in breast cancer. N Engl J Med. 2003; 348:2431–42, with permission. Copyright © 2003, Massachusetts Medical Society. All rights reserved.

This article discusses the effect of AIs on disease-free survival and the importance of distant metastasis as a first event, as a well as the implications for survival and economics.

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