ArticlesAdjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial
Introduction
Addition of a taxane to adjuvant anthracycline-based regimens improves relapse-free survival and overall survival in patients with early breast cancer.1 The Breast Cancer International Research Group (BCIRG) 001 study showed that a regimen that incorporates the taxane docetaxel reduces the risk of relapse (HR 0·72, 95% CI 0·59–0·88; p=0·001) and death (HR 0·70, 95% CI 0·53–0·91; p=0·008) compared with a standard anthracycline-based regimen in patients with node-positive, early breast cancer, as we previously reported2 after 55 months of follow-up. However, the long-term risks and benefits of adjuvant chemotherapy remain poorly understood, since many studies have not reported long-term outcomes,3 some have had substantial loss to follow-up, and most did not monitor subclinical toxic effects such as left ventricular dysfunction. Furthermore, an emerging understanding of the distinct molecular subtypes of breast cancer4 now allows for assessment of differential benefits from chemotherapy, endocrine therapy, and biologically targeted drugs.
Here we report the long-term efficacy and safety results from this large, mature, randomised study of adjuvant taxane chemotherapy, on the basis of an intention-to-treat analysis of all 1491 participants.
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Patients and study design
As previously reported,2 women eligible for this phase 3, multicentre, open label, randomised trial were aged between 18 and 70 years, had a score on the Karnofsky performance scale of 80% or more, and had undergone primary surgery (ie, mastectomy or lumpectomy) for unilateral, operable breast cancer in which clear margins were obtained, and with axillary lymph node dissection that returned at least one positive node on histological examination (from a minimum of six nodes). A complete staging
Results
Between June 11, 1997, and June 3, 1999, 1491 women from 20 countries in Europe, North and South America, Africa, and the Middle East were enrolled in the study (figure 1). Specific demographic, clinical, and molecular phenotypic characteristics of patients were well-balanced between the group assigned to receive the TAC regimen and the group assigned to receive the FAC regimen (table 1). Compliance with the study protocol was high, with fewer than 6% of participants (43 from the TAC group and
Discussion
This 10-year analysis of the BCIRG 001 study shows that adjuvant TAC for treatment of women with node-positive, early breast cancer provides long-term disease-free survival and overall survival benefits compared with FAC, with similar long-term toxic effects (panel). However, anthracycline-induced cardiotoxicity is a serious and under-recognised complication of adjuvant anthracycline-based chemotherapy regimens that warrants further attention.
The risk-to-benefit ratio of adjuvant breast cancer
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