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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials

Early Breast Cancer Trailists' Collaborative Group.

Review published: 2011.

CRD summary

This review found that the most effective of the chemotherapy regimens investigated (based on taxane plus anthracycline or higher cumulative dosage anthracycline) offered on average a one-third reduction in 10-year breast cancer mortality. Absolute benefit from this reduction depended on absolute risk without chemotherapy. This review of individual patient data was well conducted, thorough and reliable.

Authors' objectives

To review the differences in efficacy between adjuvant chemotherapy regimens for early breast cancer

Searching

Review articles were checked and discussions were held with trialists to locate trials. Systematic lists of trials produced by Union for International Cancer Control (UICC) (Geneva), National Cancer Institute (Bethesda) and UK Co-ordinating Committee on Cancer Research (London) were assessed. All conference proceedings of American Society of Clinical Oncology, American Association of Cancer Research and UICC. A computer-aided search was carried out, contact was made with manufacturers and discussions were held with at least one person from each major trial organisation. Information was sought for the period 2005 to 2010.

Study selection

Eligible studies needed to provide individual patient data on patients with breast cancer from randomised controlled trials (RCTs) that began between 1973 and 2003. Trials needed to compare taxane-based versus non-taxane-based regimens or any anthracycline-based regimen versus standard or near-standard CMF (cyclophosphamide, methotrexate, fluorouracil) or higher versus lower anthracycline dosage or polychemotherapy versus no adjuvant chemotherapy. Trials of intensive chemotherapy with stem-cell rescue or of variation only in dose-density were not included. According to original criteria developed by the Early Breast Cancer Trialists' Collaborative Group, trials conducted in USSR and Japan were excluded due to several lacking detail needed for review.

The main outcomes of interest were recurrence, breast cancer mortality and all-cause mortality.

Study selection was conducted in conjunction with trialists.

Assessment of study quality

Eligible trials needed to ensure adequate randomisation and concealment of treatment allocation. Trials were excluded if there were imbalances between treatment groups in terms of patient numbers or follow-up. Various consistency checks were conducted in conjunction with principal investigators of trials.

Data extraction

Special forms were devised to allow trialists to provide essential minimum data (identifiers, allocated treatments and duration of survival and follow-up) and optional extra data including information on recurrence.

Methods of synthesis

Trials were presented in forest plots. Graphs were plotted to illustrate absolute risks in various scenarios. Differences in breast cancer mortality were expressed as rate ratios and corresponding standard error (SE). Meta-analysis techniques were used. Subgroup analyses detailed proportional risk reductions according to patient and tumour characteristics.

Results of the review

One hundred and twenty-three trials were included (more than 100,000 participants). A large number of analyses were conducted (the main results as reported by the authors are presented here).

Trials that added four separate cycles of a taxane to a fixed anthracycline control extended treatment duration demonstrated a reduction in breast cancer mortality (RR 0.86, SE 0.04, p = 0.0005). There were no significant differences when extra cycles of a taxane were counterbalanced in control groups by extra cycles of other cytotoxic drugs.

Trials that compared standard 4AC (four cycles of doxorubicin and of cyclophosphamide three-weekly) and standard CMF had similar results. Anthracycline-based regimens with substantially higher cumulative dosage than standard 4AC were found to be superior to standard CMF (RR 0.78, SE 0.06). Trials versus no chemotherapy suggested greater mortality reductions with CAF (cyclophosphamide, doxorubicin, fluorouracil) (RR 0.64, SE 0.09) than with standard 4AC (RR 0.78, SE 0.09) and standard CMF (RR 0.76, SE 0.05).

In all analyses that involved taxane-based or anthracycline-based regimens, reductions were little affected by age, nodal status, tumour diameter or differentiation and oestrogen receptor status or tamoxifen use. Overall mortality differences were similar to those for breast cancer mortality.

Authors' conclusions

The most effective of the regimens investigated (based on taxane plus anthracycline or higher cumulative dosage anthracycline) offered on average a one-third reduction in 10-year breast cancer mortality compared with no adjuvant chemotherapy. Absolute gain from this reduction depended on absolute risk without chemotherapy.

CRD commentary

This review of individual patient data was underpinned by defined inclusion criteria. Various searching methods were used. The authors collaborated with individual trialists when conducting study selection, data extraction and when checking studies for quality. Synthesis appeared to be appropriate.

Overall this is a well conducted, thorough and reliable review of the data.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that longer follow-up of trials would help to assess the risks and benefits more reliably.

Funding

Cancer Research UK; British Heart Foundation; UK Medical Research Council.

Bibliographic details

Early Breast Cancer Trailists' Collaborative Group. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet 2011: doi:10.1016/S0140-6736(11)61625-5 . [PMC free article: PMC3273723] [PubMed: 22152853]

Indexing Status

Subject indexing assigned by NLM

MeSH

Anthracyclines /administration & dosage; Antineoplastic Combined Chemotherapy Protocols /therapeutic use; Breast Neoplasms /drug therapy /mortality; Chemotherapy, Adjuvant; Female; Humans; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Survival Rate; Taxoids /administration & dosage

AccessionNumber

12011007294

Database entry date

21/12/2011

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 22152853

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