© 2005 Oxford University Press
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Neoadjuvant Versus Adjuvant Systemic Treatment in Breast Cancer: A Meta-Analysis
Affiliations of authors: Department of Medical Oncology (DM, NP) and the Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology (JPAI), University of Ioannina School of Medicine, Ioannina, Greece; 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, Chairman, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece (e-mail: jioannid{at}cc.uoi.gr).
Background: Interest in the use of preoperative systemic treatment in the management of breast cancer has increased because such neoadjuvant therapy appears to reduce the extent of local surgery required. We compared the clinical end points of patients with breast cancer treated preoperatively with systemic therapy (neoadjuvant therapy) and of those treated postoperatively with the same regimen (adjuvant therapy) in a meta-analysis of randomized trials. Methods: We evaluated nine randomized studies, including a total of 3946 patients with breast cancer, that compared neoadjuvant therapy with adjuvant therapy regardless of what additional surgery and/or radiation treatment was used. Fixed and random effects methods were used to combine data. Primary outcomes were death, disease progression, distant disease recurrence, and loco-regional disease recurrence. Secondary outcomes were local response and conservative local treatment. All statistical tests were two-sided. Results: We found no statistically or clinically significant difference between neoadjuvant therapy and adjuvant therapy arms associated with death (summary risk ratio [RR] = 1.00, 95% confidence interval [CI] = 0.90 to 1.12), disease progression (summary RR = 0.99, 95% CI = 0.91 to 1.07), or distant disease recurrence (summary RR = 0.94, 95% CI = 0.83 to 1.06). However, neoadjuvant therapy was statistically significantly associated with an increased risk of loco-regional disease recurrences (RR = 1.22, 95% CI = 1.04 to 1.43), compared with adjuvant therapy, especially in trials where more patients in the neoadjuvant, than the adjuvant, arm received radiation therapy without surgery (RR = 1.53, 95% CI = 1.11 to 2.10). Across trials, we observed heterogeneity in the rates of complete clinical response (range = 7%–65%; P for heterogeneity of <.001), pathologic response (range = 4%–29%; P for heterogeneity of <.001), and adoption of conservative local treatment (range = 28%–89% in neoadjuvant arms, P for heterogeneity of <.001). Conclusions: Neoadjuvant therapy was apparently equivalent to adjuvant therapy in terms of survival and overall disease progression. Neoadjuvant therapy, compared with adjuvant therapy, was associated with a statistically significant increased risk of loco-regional recurrence when radiotherapy without surgery was adopted.
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Correspondence about this Article
- Re: Neoadjuvant Versus Adjuvant Systemic Treatment in Breast Cancer: A Meta-Analysis
- Sanjay Popat and Ian E. Smith
J Natl Cancer Inst 2005 97: 858.[Extract] [Full Text] [PDF]
Editorial about this Article
- Sometimes a Great Notion—An Assessment of Neoadjuvant Systemic Therapy for Breast Cancer
- Nancy E. Davidson and Monica Morrow
J Natl Cancer Inst 2005 97: 159-161.[Extract] [Full Text] [PDF]
Related Memo to the Media
- Press Release: Neoadjuvant and Adjuvant Systemic Therapy for Breast Cancer Give Equivalent Survival, Study Finds
- Sarah L. Zielinski
J Natl Cancer Inst 2005 97: 157.[Extract] [Full Text]
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D. Mauri, N. Pavlidis, and J. P. A. Ioannidis RESPONSE: Re: Neoadjuvant Versus Adjuvant Systemic Treatment in Breast Cancer: A Meta-Analysis J Natl Cancer Inst, June 1, 2005; 97(11): 858 - 859. [Full Text] [PDF]
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N. E. Davidson and M. Morrow Sometimes a Great Notion--An Assessment of Neoadjuvant Systemic Therapy for Breast Cancer J Natl Cancer Inst, February 2, 2005; 97(3): 159 - 161. [Full Text] [PDF]
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