Originally published as JCO Early Release 10.1200/JCO.2005.04.120 on July 11 2005

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Switching to Anastrozole Versus Continued Tamoxifen Treatment of Early Breast Cancer: Preliminary Results of the Italian Tamoxifen Anastrozole Trial

From the National Cancer Research Institute; University of Genoa, Genoa; S. Orsola-Malpighi Hospital, Bologna; Institute of Oncology, University of Messina, Messina; San Donato Hospital, Arezzo; S. Anna Hospital; University of Turin; University and Mauriziano Hospital, Turin; Institute of Oncology S. Luigi-S. Currò, Catania; S. Maria Hospital, Terni; Civic Hospital, Casalpusterlengo; University of Cagliari, Cagliari; University of Florence, Florence; Pierantoni Hospital, Forlì, Italy

Address reprint requests to Francesco Boccardo, MD, National Cancer Research Institute and the University of Genoa, Italy, Largo R. Benzi 10, 16132 Genoa, Italy; e-mail: f.boccardo{at}unige.it

PURPOSE: Tamoxifen, which is actually the gold standard adjuvant treatment in estrogen receptor–positive early breast cancer, is associated with an increased risk of endometrial cancer and other life-threatening events. Moreover, many women relapse during or after tamoxifen therapy because of the development of resistance. Therefore new approaches are required.

PATIENTS AND METHODS: We conducted a prospective randomized trial to test the efficacy of switching postmenopausal patients who were already receiving tamoxifen to the aromatase inhibitor anastrozole. After 2 to 3 years of tamoxifen treatment, patients were randomly assigned either to receive anastrozole 1 mg/d or to continue receiving tamoxifen 20 mg/d, for a total duration of treatment of 5 years. Disease-free survival was the primary end point. Event-free survival, overall survival, and safety were secondary end points.

RESULTS: Four hundred forty-eight patients were enrolled. All women had node-positive, estrogen receptor–positive tumors. At a median follow-up time of 36 months, 45 events had been reported in the tamoxifen group compared with 17 events in the anastrozole group (P = .0002). Disease-free and local recurrence-free survival were also significantly longer in the anastrozole group (hazard ratio [HR] = 0.35; 95% CI, 0.18 to 0.68; P = .001 and HR = 0.15; 95% CI, 0.03 to 0.65; P = .003, respectively). Overall, more adverse events were recorded in the anastrozole group compared with the tamoxifen group (203 v 150, respectively; P = .04). However, more events were life threatening or required hospitalization in the tamoxifen group than in the anastrozole group (33 of 150 events v 28 of 203 events, P = .04).

CONCLUSION: Switching to anastrozole after the first 2 to 3 years of treatment is well tolerated and significantly improves event-free and recurrence-free survival in postmenopausal patients with early breast cancer.

Presented in part at the 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 3-6, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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  JCO 2005 23: 4850-4852 [Full Text]

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