Adjuvant chemotherapy for early female breast cancer: A systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline

S. Gandhi, G.G. Fletcher, A. Eisen, M. Mates, O.C. Freedman, S.F. Dent, M.E. Trudeau



The Program in Evidence-Based Care (PEBC) of Cancer Care Ontario (CCO) has recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer.  The evidence for this guideline was compiled using a systematic review to answer the question:  “What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?”  This question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and human epidermal growth factor receptor 2 (HER2) directed therapy.


A systematic review was performed using the MEDLINE and EMBASE databases for the period January 2008 to May 2014.  The SAGE Directory of Cancer Guidelines and websites of major oncology guideline organizations were also searched.  The basic search terms were “breast cancer” and “systemic therapy” (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and was limited to randomized controlled trials (RCTs), guidelines, systematic reviews, and meta-analyses. 


Several hundred documents were retrieved that met the inclusion criteria; the Early Breast Cancer Trialists Collaborative Group (EBCTCG) meta-analyses encompassed many of the RCTs found. Several additional studies which met the inclusion criteria were included, as well as other guidelines and systematic reviews.  Chemotherapy was largely reviewed as three classes of agents: anti-metabolite based regimens (e.g., CMF), anthracyclines, and taxane-based regimens. Single-agent chemotherapy in general is not recommended for the adjuvant treatment of breast cancer in any patient population.  Anthracycline and taxane-based polychemotherapy regimens are overall considered superior to earlier generation regimens, with the most significant impact on patient survival outcomes. Various regimens with disparate anthracycline and taxane doses and schedules are options; in general, paclitaxel given every 3 weeks is inferior. Evidence does not support the use of bevacizumab in the adjuvant setting; other systemic therapy agents such as metformin and vaccines remain under investigation. Adjuvant bisphosphonates for menopausal women will be discussed in later work.  


The results of this systematic review represent a comprehensive compilation of high-level evidence which was the basis for the 2014 PEBC CCO guideline on systemic therapy for early breast cancer. The use of cytotoxic chemotherapy is presented here; the results addressing endocrine therapy and HER-2 targeted treatment, as well as the final clinical practice recommendations, are published separately in this issue.


early breast cancer; systemic treatment; chemotherapy; adjuvant; cytotoxic; drug therapy


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ISSN: 1198-0052 (Print) ISSN: 1718-7729 (Online)