What is the issue?
Breast cancer is the most common cancer in women worldwide. The two main treatment strategies are either breast-conserving therapy or mastectomy. To decrease the risk of recurrence and improve survival rates, standard care involves adjuvant radiotherapy (treatment with ionising radiation) after breast-conserving surgery. Adjuvant radiotherapy consists mainly of four to five weeks of whole-breast irradiation followed by an extra dose 'boost' to the tumour bed because breast cancer tends to come back in the same area where it was removed. Apart from maintaining the breast and achieving breast cancer control, a satisfying physical appearance (cosmesis) is important in breast-conserving therapy.
Why does it matter?
Guidelines for use of the tumour bed boost are often not clear-cut. Even though it is technically feasible to treat all women with a boost to the tumour bed after whole-breast irradiation, it remains unclear whether this is necessary or whether it may do more harm than good. Possible consequences of adding a boost dose to the tumour bed are poor cosmesis, as well as higher treatment costs and increased treatment times.
We asked whether not giving a tumour bed boost dose after whole-breast irradiation and breast-conserving surgery is as good as giving the boost dose. Omission of a boost to the tumour bed would need to have equivalent cancer control compared with giving a boost to the tumour bed. It would also be important that omission of a boost to the tumour bed results in fewer side effects compared with giving the tumour bed boost dose.
We found 5 studies involving a total of 8325 women. Our evidence is current to 1 March 2017. Local recurrence was less common with a tumour bed boost (low-quality evidence). There was no evidence of a difference in disease-free or overall survival with or without the administration of the tumour bed boost (low- and moderate-quality evidence, respectively). Cosmesis scored by a panel appeared to be worse for the tumour bed boost group (low-quality evidence). There was no difference in physician-scored cosmesis or percentage of breast retraction.
This means that adding a boost to the tumour bed increases the local control rate at a possible cost of worse cosmesis.
It appears that local control rates are increased with the boost to the tumour bed, but we found no evidence of a benefit for other oncological outcomes. Subgroup analysis including women older than 40 years of age yielded similarly significant results. Objective percentage of breast retraction assessment appears similar between groups. It appears that the cosmetic outcome is worse with the boost to the tumour bed, but only when measured by a panel, not when assessed by a physician.
Breast-conserving therapy, involving breast-conserving surgery followed by whole-breast irradiation and optionally a boost to the tumour bed, is a standard therapeutic option for women with early-stage breast cancer. A boost to the tumour bed means that an extra dose of radiation is applied that covers the initial tumour site. The rationale for a boost of radiotherapy to the tumour bed is that (i) local recurrence occurs mostly at the site of the primary tumour because remaining microscopic tumour cells are most likely situated there; and (ii) radiation can eliminate these causative microscopic tumour cells. The boost continues to be used in women at high risk of local recurrence, but is less widely accepted for women at lower risk. Reasons for questioning the boost are twofold. Firstly, the boost brings higher treatment costs. Secondly, the potential adverse events are not negligible. In this Cochrane Review, we investigated the effect of the tumour bed boost on local control and side effects.
To assess the effects of tumour bed boost radiotherapy after breast-conserving surgery and whole-breast irradiation for the treatment of breast cancer.
We searched the Cochrane Breast Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to 1 March 2017), Embase (1980 to 1 March 2017), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov on 1 March 2017. We also searched the European Society of Radiotherapy and Oncology Annual Meeting, the St Gallen Oncology Conferences, and the American Society for Radiation Oncology Annual Meeting for abstracts.
Randomised controlled trials comparing the addition and the omission of breast cancer tumour bed boost radiotherapy.
Two review authors (IK and CW) performed data extraction and assessed risk of bias using Cochrane's 'Risk of bias' tool, resolving any disagreements through discussion. We entered data into Review Manager 5 for analysis and applied GRADE to assess the quality of the evidence.
We included 5 randomised controlled trials analysing a total of 8325 women.
Local control appeared to be better for women receiving a tumour bed boost compared to no tumour bed boost (hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.55 to 0.75; 5 studies, 8315 women, low-quality evidence). Overall survival did not differ with or without a tumour bed boost (HR 1.04, 95% CI 0.94 to 1.14; 2 studies, 6342 women, moderate-quality evidence). Disease-free survival did not differ with or without a tumour bed boost (HR 0.94, 95% CI 0.87 to 1.02; 3 studies, 6549 women, low-quality evidence). Late toxicity scored by means of percentage of breast retraction assessment did not differ with or without a tumour bed boost (mean difference 0.38, 95% CI -0.18 to 0.93; 2 studies, 1526 women, very low-quality evidence). Cosmesis scored by a panel was better (i.e. excellent or good compared to fair or poor) in the no-boost group (odds ratio (OR) 1.41, 95% CI 1.07 to 1.85; 2 studies, 1116 women, low-quality evidence). Cosmesis scored by a physician did not differ with or without a tumour bed boost (OR 1.58, 95% CI 0.93 to 2.69; 2 studies, 592 women, very low-quality evidence).
We excluded two studies in a sensitivity analysis of local recurrence (because the biological equivalent dose (BED) to the tumour bed was lower, in situ tumours were included, or there was a high risk of selective reporting bias or blinding of outcome assessment bias), which resulted in a HR of 0.62 (95% CI 0.52 to 0.73; 3 studies, 6963 women, high-quality evidence). Subgroup analysis including women older than 40 years of age yielded a HR of 0.65 (95% CI 0.53 to 0.81; 2 studies, 5058 women, high-quality evidence).
We found no data for the outcomes of acute toxicity, quality of life, or costs.