Fast track — ArticlesEffects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
Introduction
In early breast cancer, disease is detected only in the breast or, in the case of women with node-positive disease, the breast and locoregional lymph nodes, and all detected disease can be removed surgically. However, undetected deposits of disease may remain either locally or at distant sites that, if untreated, could over the next 5, 10, 15, or more years develop into a life-threatening clinical recurrence. Breast cancer is unusual in that although the risk of distant recurrence is greatest during the first decade, it may still be substantial during the second decade after diagnosis. The main aim of systemic adjuvant treatment is to control any remaining deposits of disease, reduce the recurrence rate, and improve long-term survival.
Over the past few decades, many randomised trials have been undertaken of various treatments for early breast cancer, but the duration of follow-up differs greatly between different trials and between different patients in the same trial. Hence, meta-analyses of the effects of such treatments on long-term outcome (during and, where possible, after the first decade) in various types of patient should ideally involve central review of data on time to recurrence, death, or end of follow-up from every individual patient in every trial. Moreover, as the numbers randomised continue to increase, and follow-up on those already randomised continues to accumulate in many trials, such meta-analyses should ideally be updated every few years.
The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) was, therefore, set up in 1984–851 to coordinate quinquennial worldwide meta-analyses2, 3, 4, 5, 6, 7, 8, 9, 10 of centrally collected data from every woman in all randomised trials of the treatment of early breast cancer that had, at the time of the analysis, already been running for at least 5 years. The present report is of the final results from the year 2000 EBCTCG meta-analyses of the trials of systemic adjuvant treatments (chemotherapy, endocrine therapy, or chemoendocrine therapy) that had begun in or before 1995. The corresponding meta-analyses of the trials of local treatments (surgery or radiotherapy) will be reported separately.
This is the fourth quinquennial cycle of this worldwide collaboration. It addresses many of the same questions as the previous cycles, but with more trials, more patients, better ascertainment of causes of death, and, particularly, longer follow-up. Hence, there is now substantially more evidence than before8, 9, 10 comparing the effects on 10-year survival of different adjuvant regimens (eg, anthracycline-based vs other chemotherapy regimens; longer vs shorter tamoxifen regimens; ovarian ablation or suppression in addition to chemotherapy vs chemotherapy alone).
From the older trials of adjuvant treatment versus not, where the 10-year survival differences were already definite,7, 8 the 15-year differences between treatment and control are now stable enough to be compared usefully with the 10-year differences. Thus, from the first and second decades of follow-up in various types of trial, a clearer picture is now emerging of what the lifelong risks and benefits could eventually be.
Section snippets
Methods
Trial identification and data handling procedures have been described previously.3, 4 Information was sought from all randomised trials that had started by 1995. This report describes all the trials of more than 1 month9 of systemic adjuvant therapy in which two treatment arms provided an unconfounded comparison of: (a) single-agent chemotherapy versus no adjuvant chemotherapy; (b) polychemotherapy versus no adjuvant chemotherapy; (c) anthracycline-based polychemotherapy versus standard
Results
The panel describes the format of figures and tables in this report. The study website provides supplementary information to every figure and table in the form of annex-figures and table appendices, which are also available in webappendix 1 (with explanations of what they are in webappendix 2). A list describing every trial separately can be found in webappendix 3.
Results are given first for chemotherapy, then for tamoxifen, and then for ovarian ablation or suppression. Table 1 shows the
Tamoxifen versus no tamoxifen
Figure 7 summarises the effects of 1–2 years of tamoxifen and of about 5 years of tamoxifen in the trials that compared tamoxifen versus no adjuvant tamoxifen. Because of the established relevance of the hormone receptor status of the primary tumour, the analyses are subdivided by ER status, classified as ER-poor, ER-positive, and ER-unknown. Procedures for measuring receptor status continue to evolve, so current and future measurements could well be more predictive of response. But, even
Ovarian ablation or suppression
Almost 8000 women younger than 50 years of age with ER-positive or ER-unknown disease have been randomised into trials of ovarian ablation by surgery or irradiation (4317 women, 63% ER-untested, mean follow-up 8 woman-years) or of ovarian suppression by some years of treatment with a luteinising-hormone-releasing-hormone inhibitor (LHRHI; 3408 women, 26% ER-untested, mean follow-up 5 years; figure 12).
Overall, there is a definite effect of ovarian ablation or suppression both on recurrence
15-year survival
The present analyses of systemic adjuvant treatment for early breast cancer involve a total of almost 150 000 women in 200 randomised trials, many with long-term follow-up. This collaboration, which could at first assess only short-term survival differences, has now continued for 20 years, providing increasingly reliable evidence about the 15-year risks and benefits of various treatments that were being tested in the 1980s (eg, about 6 months of treatment with anthracycline-based combinations
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Collaborators listed at end of report