© The Author 2006. Published by Oxford University Press.
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Survival With Aromatase Inhibitors and Inactivators Versus Standard Hormonal Therapy in Advanced Breast Cancer: Meta-analysis
Affiliations of authors: Department of Medical Oncology (DM, NP) and Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology (NPP, JPAI), University of Ioannina School of Medicine, Ioannina, Greece; Biomedical Research Institute, Foundation for Research and Technology-Hellas, Ioannina, Greece (JPAI); Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, MA (JPAI)
Correspondence to: John P. A. Ioannidis, MD, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece (e-mail: jioannid{at}cc.uoi.gr).
Background: Aromatase inhibitors and inactivators have been extensively tested in patients with advanced breast cancer, but it is unclear whether they offer any survival benefits compared with standard hormonal treatment with tamoxifen or progestagens. We performed a meta-analysis of randomized controlled trials that compared several generations of aromatase inhibitors and inactivators with standard hormonal treatment in patients with advanced breast cancer. Methods: The endpoint that we assessed was survival. Trials were located through searches of PubMed and Cochrane Library (last update March 2006). Relative hazards (RHs) were summarized across trials through fixed- and random-effects analyses, and heterogeneity was assessed with the Q and I2 statistics. All statistical tests were two-sided. Results: Twenty-five different comparisons, with a total of 8504 patients, were included in the meta-analysis. We found statistically significant survival benefits with third-generation aromatase inhibitors and inactivators (vorozole, letrozole, examestane, and anastrazole) (RH = 0.87, 95% confidence interval [CI] = 0.82 to 0.93; P<.001) but not with first-generation (aminoglutethimide) or second-generation (formestane and fadrozole) agents. The difference in the summary effects between these two groups of trials was statistically significant (P = .04). The survival benefit with third-generation agents in first-line trials, in which these agents were compared with tamoxifen (11% RH reduction, 95% CI = 1% to 19%; P = .03), was identical to their benefit in second- and subsequent-line trials in which these agents were compared with other treatments (14% RH reduction, 95% CI = 6% to 21%; P<.001). Conclusions: Inhibition of the aromatase system, in particular with third-generation aromatase inhibitors and inactivators, appears to be associated with statistically significant improved survival of patients with advanced breast cancer compared with standard hormonal treatments.
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Correspondence about this Article
- Re: Survival With Aromatase Inhibitors and Inactivators Versus Standard Hormonal Therapy in Advanced Breast Cancer: Meta-analysis
- Emilio Bria, Paolo Carlini, Francesco Cognetti, Edmondo Terzoli, and Diana Giannarelli
J Natl Cancer Inst 2007 99: 176.[Extract] [Full Text] [PDF]
Editorial about this Article
- Aromatase Inhibitors for the Treatment of Breast Cancer: Is Tamoxifen of Historical Interest Only?
- Catherine H. Van Poznak and Daniel F. Hayes
J Natl Cancer Inst 2006 98: 1261-1263.[Extract] [Full Text] [PDF]
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