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Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormonesensitive early-stage breast cancer: a meta-analysis
Author(s): Jonat W (Jonat, Walter), Gnant M (Gnant, Michael), Boccardo F (Boccardo, Francesco), Kaufmann M (Kaufmann, Manfred), Rubagotti A (Rubagotti, Alessandro), Zuna I (Zuna, Ivan), Greenwood M (Greenwood, Mike), Jakesz R (Jakesz, Raimund)
Source: LANCET ONCOLOGY    Volume: 7    Issue: 12    Pages: 991-996    Published: DEC 2006  
Times Cited: 88     References: 26     
Abstract: Background For more than 20 years, tamoxifen has been the mainstay of adjuvant endocrine therapy for women with hormone-sensitive early-stage breast cancer. However, not only does tamoxifen have potential side-effects such as an increased risk of endometrial cancer and thromboembolic events, but patients can also develop resistance to the drug. We aimed to investigate whether switching treatment of postmenopausal women with such breast cancer to anastrozole after 2-3 years of tamoxifen would be more effective than continuing on tamoxifen for a total of 5 years.

Methods We did a meta-analysis of three clinical trials-the Austrian Breast and Colorectal Cancer Study Group (ABCSG 8), Arimidex-Nolvadex (ARNO 95), and the Italian Tamoxifen Anastrozole (ITA) studies-in which postmenopausal women with histologically confirmed, hormone-sensitive early-stage breast cancer were randomised to 1 mg/day anastrozole (n=2009) after 2-3 years of tamoxifen treatment or to continued 20 or 30 mg/day tamoxifen (n=1997). We analysed the data with a stratified Cox proportional hazards model with the covariates of age, tumour size, nodal status, grade, surgery, and chemotherapy.

Findings Patients who switched to anastrozole had fewer disease recurrences (92 vs 159) and deaths (66 vs 90) than did those who remained on tamoxifen, resulting in significant improvements in disease-free survival (hazard ratio 0 59 [95% CI 0.48-0.74]; p<0.0001), event-free survival (0.55 [0.42-0.71]; p<0.0001), distant recurrence-free survival (0 61 [0.45-0.83]; p=0.002), and overall survival (0 .71 [0.52-0.98]; p=0.04).

Interpretation Our results show that the clinical benefits in terms of event-free survival seen in individual trials for those patients who switched to anastrozole translate into a benefit in overall survival. These findings confirm that clinicians should consider switching postmenopausal women who have taken adjuvant tamoxifen for 2-3 years to anastrozole.

Document Type: Article
Language: English
Reprint Address: Jonat, W (reprint author), Univ Kiel, Clin Gynecol & Obstet, Brunswiker Str 10, D-24105 Kiel, Germany
Addresses:
1. Univ Kiel, Clin Gynecol & Obstet, D-24105 Kiel, Germany
2. Med Univ Vienna, Vienna, Austria
3. Univ Genoa, I-16126 Genoa, Italy
4. Univ Frankfurt, D-6000 Frankfurt, Germany
5. Inst Stat SKM, Wiesbaden, Germany
6. AstraZeneca, Macclesfield, Cheshire England
Publisher: LANCET LTD, 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
Subject Category: Oncology
IDS Number: 112UG
ISSN: 1470-2045
DOI: 10.1016/S1470-2045(06)70948-2
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