title: Sequencing of chemotherapy and radiation therapy for early breast cancer.
abstract: BACKGROUND
  After surgery for localised breast cancer, adjuvant radiotherapy improves both local control and breast cancer specific survival. In patients at risk of harbouring micro-metastatic disease, adjuvant chemotherapy improves 15-year survival. However, the best sequence of administering these two types of adjuvant therapy for early stage breast cancer is not clear.
  
  
  OBJECTIVE
  To determine the effects of different sequencing of chemotherapy and radiotherapy for women with early breast cancer.
  
  
  METHODS
  We searched the Cochrane Breast Cancer Group Specialized Register (10 March 2005). Details of the search strategy and methods of coding are described in the Group's module in The Cochrane Library. We extracted studies that had been coded as 'early', 'chemotherapy' and 'radiotherapy'.
  
  
  METHODS
  Randomised controlled trials evaluating different sequencing of chemotherapy and radiotherapy were included.
  
  
  METHODS
  We assessed the eligibility and quality of the identified studies and extracted data from the published reports of the included studies. We derived odds ratios (OR) and risk ratios from the available numerical data. Hazard ratios were extracted directly from text. Toxicity data were extracted, where reported. We used a fixed-effect model for meta-analysis and conducted analyses on the basis of the method of sequencing of the two treatments.
  
  
  RESULTS
  Three trials reporting two different sequencing comparisons were identified. There were no significant differences between the various methods of sequencing adjuvant therapy for survival, distant metastases or local recurrence, based on 853 randomised patients in two trials. One of these two trials (647 women) provided data on toxicity. Haematological toxicity (OR 1.43, confidence interval (CI) 1.01 to 2.03) and oesophageal toxicity (OR 1.44, CI 1.03 to 2.02) were significantly increased with concurrent therapy, and nausea and vomiting were significantly decreased (OR 0.70, CI 0.50 to 0.98). Other measures of toxicity did not differ between the two types of sequencing. On the basis of one trial (244 women), radiotherapy before chemotherapy was associated with a significantly increased risk of neutropenic sepsis (OR 2.96, 95% CI 1.26 to 6.98) compared with chemotherapy before radiotherapy, but other measures of toxicity were not significantly different.
  
  
  CONCLUSIONS
  The data included in this review, from three well conducted randomised trials, suggest that different methods of sequencing chemotherapy and radiotherapy do not appear to have a major effect on survival or recurrence for women with breast cancer if radiation therapy is commenced within 7 months after surgery.
authors.affiliation: Queensland Radium Institute Mater Centre, Southern Zone Oncology Service, Raymond Terrace, Brisbane, QLD, Australia. hickmenn@bigpond.net.au
authors.forename: B E
authors.initials: BE
authors.lastname: Hickey
authors.forename: D
authors.initials: D
authors.lastname: Francis
authors.forename: M H
authors.initials: MH
authors.lastname: Lehman
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant / Q000379:methods*; D005260:Female; D006801:Humans; D018714:Radiotherapy, Adjuvant / Q000379:methods*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors