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.
Objectives
To determine the effects of different sequencing of chemotherapy and radiotherapy for women with early breast cancer.
Search 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'.
Selection criteria
Randomised controlled trials evaluating different sequencing of chemotherapy and radiotherapy were included.
Data collection and analysis
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.
Main 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.
Authors' 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.
PICOs
Plain language summary
Sequencing of chemotherapy and radiotherapy for women following surgery for early breast cancer
Both chemotherapy and radiotherapy reduce the risk of breast cancer recurring and the risk of dying from breast cancer. Generally these therapies are given after surgery but there is uncertainty about whether they should be given at the same time (concurrently) or one after the other (sequentially). If they are used sequentially, the radiotherapy or the chemotherapy could be used first and concerns have been expressed that the effectiveness of the therapy that is delayed might be reduced. However, it has also been suggested that using chemotherapy and radiotherapy at the same time will be less beneficial than keeping them separate. This review examined current evidence on the best way to administer chemotherapy and radiotherapy following breast conserving surgery. We were able to include three randomised trials. Two of these, with a total of 853 women, assessed radiotherapy and chemotherapy given at the same time versus chemotherapy given first followed by radiotherapy. The third trial randomised 244 women to radiotherapy followed by chemotherapy versus chemotherapy followed by radiotherapy. The evidence produced by these three well conducted trials suggests that recurrence of a woman's cancer and her chances of dying from breast cancer are similar regardless of the order of the treatments, provided that both radiotherapy and chemotherapy are commenced within seven months of the surgery. The trials provided limited information regarding adverse events, side effects, or quality of life associated with the different sequences of treatment, but the limited evidence available does suggest that the frequency and severity of side effects of chemotherapy and radiotherapy are similar regardless of which sequence is used. It should be noted, however, that the women in these trials were treated, on average, ten years ago. As a result the trials do not assess the modern types of radiotherapy, and newer types of chemotherapy (such as taxanes) or other drugs (such as Herceptin). We will add relevant trials which include these newer treatments to future updates of this review.
