Post-operative radiotherapy for ductal carcinoma in situ of the breast
Editorial Group: Cochrane Breast Cancer Group
Published Online: 21 NOV 2013
Assessed as up-to-date: 2 JUN 2011
Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
How to Cite
Goodwin A, Parker S, Ghersi D, Wilcken N. Post-operative radiotherapy for ductal carcinoma in situ of the breast. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD000563. DOI: 10.1002/14651858.CD000563.pub7.
- Publication Status: Stable (no update expected for reasons given in 'What's new')
- Published Online: 21 NOV 2013
The addition of radiotherapy (RT) following breast conserving surgery (BCS) was first shown to reduce the risk of ipsilateral recurrence in the treatment of invasive breast cancer. Ductal carcinoma in situ (DCIS) is a pre-invasive lesion. Recurrence of ipsilateral disease following BCS can be either DCIS or invasive breast cancer. Randomised controlled trials (RCTs) have shown that RT can reduce the risk of recurrence, but assessment of potential long-term complications from addition of RT following BSC for DCIS has not been reported for women participating in RCTs.
To summarise the data from RCTs testing the addition of RT to BCS for treatment of DCIS to determine the balance between the benefits and harms.
We searched the Cochrane Breast Cancer Group Specialised Register (2 June 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 1), MEDLINE (2 June 2011), EMBASE (2 June 2011) and the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP; 2 June 2011). Reference lists of articles and handsearching of ASCO (2007), ESMO (2002 to 2007), and St Gallen (2005 to 2007) conferences were performed.
RCTs of breast conserving surgery with and without radiotherapy in women at first diagnosis of pure ductal carcinoma in situ (no invasive disease present).
Data collection and analysis
Two authors independently assessed each potentially eligible trial for inclusion and its quality. Two authors also independently extracted data from published Kaplan-Meier analysis (survival curves) and reported summary statistics. Data were extracted and pooled for four trials. Data for planned subgroups were extracted and pooled for analysis.There were insufficient data to pool for long-term toxicity from radiotherapy.
Four RCTs involving 3925 women were identified and included in this review. All were high quality with minimal risk of bias. Three trials compared the addition of RT to BCS. One trial was a two by two factorial design comparing the use of RT and tamoxifen, each separately or together, in which participants were randomised in at least one arm. Analysis confirmed a statistically significant benefit from the addition of radiotherapy on all ipsilateral breast events (hazards ratio (HR) 0.49; 95% CI 0.41 to 0.58, P < 0.00001), ipsilateral invasive recurrence (HR 0.50; 95% CI 0.32 to 0.76, p=0.001) and ipsilateral DCIS recurrence (HR 0.61; 95% CI 0.39 to 0.95, P = 0.03). All the subgroups analysed benefited from addition of radiotherapy. No significant long-term toxicity from radiotherapy was found. No information about short-term toxicity from radiotherapy or quality of life data were reported.
This review confirms the benefit of adding radiotherapy to breast conserving surgery for the treatment of all women diagnosed with DCIS. No long-term toxicity from use of radiotherapy was identified.
Plain language summary
Post-operative radiotherapy for ductal carcinoma in situ
Ductal carcinoma in situ (DCIS) is characterised by the development of cancerous cells in the milk ducts of the breast and is commonly diagnosed by mammography screening. Surgical removal of the breast offers a good prognosis, however many women and clinicians prefer breast conserving surgery (BCS), the removal of the DCIS plus a rim of normal breast tissue, as there is no guarantee that DCIS will progress to invasive cancer. This approach means that most of the normal breast is saved. The main risk of inadequately removing all the DCIS is either a recurrence of DCIS or the development of invasive breast cancer at a later time with the risk that this can progress to metastatic disease (cancer that has spread). Radiotherapy (RT) is treatment using ionising radiation. Giving RT after BCS is thought to reduce the risk of developing recurrent disease (either DCIS or invasive breast cancer).
This review aimed to assess both the benefit of adding RT to treatment and any potential long or short-term harm it may cause. Short-term harm includes skin rash and redness, or inflammation of lung tissue. Potential long-term side effects from RT include vascular disease (heart and major blood vessel disease), damage to the lungs, development of lung cancer, or osteoradionecrosis (bone damage resulting in bone death).
The review identified four large randomised controlled trials (3925 women) that compared treatment with breast conserving surgery alone and breast conserving surgery with the addition of RT. The addition of RT reduced the risk of a recurrence of either DCIS or invasive cancer in the treated breast by 51%.
Older trials of breast conserving surgery followed by RT for invasive breast cancer have shown long-term toxicity from the addition of RT. We found no evidence of increased toxicity from the use of RT although some trials did not report on the causes of non-breast cancer deaths (deaths which potentially could be related to side effects). The number of non-breast cancer deaths reported were similar in both radiotherapy and control groups. Changes in delivery of RT between older and more recent trials and a subsequent decrease in exposure of normal tissue may account for this finding. Longer follow up of trial participants is required before a definite conclusion can be drawn, however radiotherapy techniques are continuing to improve and future patients are likely to experience a further decrease in exposure of nearby normal tissues. Overall survival was high and similar between each group whether radiotherapy was used or not. There were no reports of short-term toxicity from use of radiotherapy, or quality of life data.