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Polychemotherapy for Early Breast Cancer: Results From the International Adjuvant Breast Cancer Chemotherapy Randomized Trial
The Adjuvant Breast Cancer Trials Collaborative GroupCorrespondence to: Judith M. Bliss, MSc, The Institute of Cancer Research—Clinical Trials and Statistics Unit, Section of Clinical Trials, Sir Richard Doll Bldg, Cotswold Rd, Sutton, Surrey SM2 5NG, UK (e-mail: ABC-icrctsu{at}icr.ac.uk).
Background: Survival of patients with early-stage breast cancer is improved following treatment with single-modality tamoxifen, ovarian ablation or suppression, or chemotherapy. The Adjuvant Breast Cancer Trials were designed to ascertain any additional benefits of combined treatment.
Methods: The Adjuvant Breast Cancer Chemotherapy Trial was a randomized phase III trial in which patients with early-stage breast cancer who were receiving prolonged (5 years) tamoxifen treatment, with or without ovarian ablation or suppression, were randomly assigned to standard chemotherapy versus none. Trial endpoints included relapse-free and overall survival. Hazard ratios (HRs) were derived from Cox models, and all statistical tests were two-sided.
Results: Between 1992 and 2000, 1991 patients between the ages of 26 and 81 years were randomly assigned (987 to chemotherapy, 1004 to no chemotherapy) from 106 UK and 16 non-UK centers. Nine hundred seven (92%) patients received chemotherapy as allocated (87% received cyclophosphamide, methotrexate, and 5-fluorouracil; 11% received anthracycline-containing regimens). A total of 244 of the 619 premenopausal patients received elective ovarian ablation or suppression. Chemotherapy improved relapse-free survival (relapse in the chemotherapy group versus no-chemotherapy group, 298 events versus 332 events, HR = 0.86, 95% confidence interval [CI] = 0.73 to 1.01; P = .06) and overall survival (death from any cause in the chemotherapy group versus no-chemotherapy group, 243 events versus 282 events, HR = 0.83, 95% CI = 0.70 to 0.99; P = .03) after adjustment for nodal status, estrogen receptor status, and age. Subgroup analyses showed that the benefit of chemotherapy was greatest in younger women (<50 years) and in particular for premenopausal women not receiving ovarian ablation or suppression.
Conclusion: Modest yet sustainable benefits for chemoendocrine therapy occur in women with breast cancer. However, the full impact on overall survival may not emerge for several years.
| CONTEXT AND CAVEATS Prior knowledge Single-modality treatment with tamoxifen, ovarian suppression or ablation, or chemotherapy improves the survival of women with early-stage breast cancer. Study design Randomized controlled phase III clinical trial of tamoxifen treatment in combination with chemotherapy and/or ovarian ablation or suppression. Contributions Women who had chemotherapy had improved relapse-free and overall survival compared with those who did not have chemotherapy. Improvements were seen especially among women younger than age 50 years and premenopausal women who did not receive ovarian ablation or suppression. Implications Chemotherapy combined with endocrine therapy (tamoxifen) may improve outcomes of women with early-stage breast cancer. Limitations Due to improvements in breast cancer treatment since the study began, current regimens and criteria for treatment are different from those used in the study. Thus, the benefits of current therapies may be greater than those observed in this study.
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Manuscript received June 14, 2006; revised January 24, 2007; accepted February 22, 2007.
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J Natl Cancer Inst 2007 99: 1416.
J Natl Cancer Inst 2007 99: 493.
J Natl Cancer Inst 2007 99: 493.
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