Partial breast irradiation for early breast cancer
Abstract
Background
Breast‐conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiotherapy (RT). RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence. Most true recurrences occur in the same quadrant as the original tumour. Whole breast radiotherapy (WBRT) may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane review, we investigated the delivery of radiation to a limited volume of the breast around the tumour bed (partial breast irradiation (PBI)) sometimes with a shortened treatment duration (accelerated partial breast irradiation (APBI)).
Objectives
To determine whether PBI/APBI is equivalent to or better than conventional or hypo‐fractionated WBRT after breast‐conserving therapy for early‐stage breast cancer.
Search methods
We searched the Cochrane Breast Cancer Group Specialized Register (4 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 5), MEDLINE (January 1966 to 4 May 2015), EMBASE (1980 to 4 May 2015), CINAHL (4 May 2015) and Current Contents (4 May 2015). We searched the International Standard Randomised Controlled Trial Number Register (5 May 2015), the World Health Organization's International Clinical Trials Registry Platform (4 May 2015) and ClinicalTrials.gov (17 June 2015). We searched for grey literature: OpenGrey (17 June 2015), reference lists of articles, several conference proceedings and published abstracts, and applied no language restrictions.
Selection criteria
Randomized controlled trials (RCTs) without confounding, that evaluated conservative surgery plus PBI/APBI versus conservative surgery plus WBRT. Published and unpublished trials were eligible.
Data collection and analysis
Two review authors (BH and ML) performed data extraction and used Cochrane's 'Risk of bias' tool, and resolved any disagreements through discussion. We entered data into Review Manager 5 for analysis.
Main results
We included seven RCTs and studied 7586 women of the 8955 enrolled.
Local recurrence‐free survival appeared worse for women receiving PBI/APBI compared to WBRT (hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.11 to 2.35; six studies, 6820 participants, low‐quality evidence). Cosmesis (physician‐reported) appeared worse with PBI/APBI (odds ratio (OR) 1.51, 95% CI 1.17 to 1.95, five studies, 1720 participants, low‐quality evidence). Overall survival did not differ with PBI/APBI (HR 0.90, 95% CI 0.74 to 1.09, five studies, 6718 participants, high‐quality evidence).
Late radiation toxicity (subcutaneous fibrosis) appeared worse with PBI/APBI (OR 6.58, 95% CI 3.08 to 14.06, one study, 766 participants, moderate‐quality evidence). Acute skin toxicity appeared reduced with PBI/APBI (OR 0.04, 95% CI 0.02 to 0.09, two studies, 608 participants). Telangiectasia (OR 26.56, 95% CI 3.59 to 196.51, 1 study, 766 participants) and radiological fat necrosis (OR 1.58, 95% CI 1.02 to 2.43, three studies, 1319 participants) appeared worse with PBI/APBI. Late skin toxicity (OR 0.21, 95% CI 0.01 to 4.39, two studies, 608 participants) and breast pain (OR 2.17, 95% CI 0.56 to 8.44, one study, 766 participants) appeared not to differ with PBI/APBI.
'Elsewhere primaries' (new primaries in the ipsilateral breast) appeared more frequent with PBI/APBI (OR 3.97, 95% CI 1.51 to 10.41, three studies, 3009 participants).
We found no clear evidence of a difference for the comparison of PBI/APBI with WBRT for the outcomes of: cause‐specific survival (HR 1.08, 95% CI 0.73 to 1.58, five studies, 6718 participants, moderate‐quality evidence), distant metastasis‐free survival (HR 0.94, 95% CI 0.65 to 1.37, four studies, 3267 participants, moderate‐quality evidence), relapse‐free survival (HR 1.36, 95% CI 0.88 to 2.09, three studies, 3811 participants), loco‐regional recurrence‐free survival (HR 1.80, 95% CI 1.00 to 3.25, two studies, 3553 participants) or mastectomy rates (OR 1.20, 95% CI 0.77 to 1.87, three studies, 4817 participants, low‐quality evidence). Compliance was met: more than 90% of the women in all studies received the RT they were assigned to receive. We found no data for the outcomes of costs, quality of life or consumer preference.
Authors' conclusions
It appeared that local recurrence and 'elsewhere primaries' (new primaries in the ipsilateral breast) are increased with PBI/APBI (the difference was small), but we found no evidence of detriment to other oncological outcomes. It appeared that cosmetic outcomes and some late effects were worse with PBI/APBI but its use was associated with less acute skin toxicity. The limitations of the data currently available mean that we cannot make definitive conclusions about the efficacy and safety or ways to deliver of PBI/APBI. We await completion of ongoing trials.
PICOs
Plain language summary
Partial breast irradiation for early breast cancer
What is the issue?
Women with early breast cancer who choose to keep their breast need to have radiotherapy (RT) as well as surgery to remove the cancer to make sure it does not regrow in the breast. RT is treatment with high energy x‐rays. Having RT for breast cancer usually means 25 to 30 visits to the RT department, five times per week.
If breast cancer does regrow in the same breast (called local recurrence), it tends to come back in the area it was removed from. Women can also grow a new cancer (new 'elsewhere primary') in another part of the same breast. We are not sure if the RT given to stop cancer regrowth where the first cancer was does stop the growth of 'elsewhere primaries'.
Breast cancer is the most common cancer that women get. When women choose to keep their breast, it is important that they are happy with how it looks after treatment (cosmesis).
Why does it matter?
We always want to treat the smallest area we can with RT because this means fewer side effects. Treating only part of the breast could mean that RT might be able to be used again in another part of the same breast if needed. New ways of giving RT mean that treating part of the breast can be done with fewer treatments. This is likely to be easier for women and cost less money.
We asked if giving RT to part of the breast (called partial breast irradiation (PBI)) is as good as giving RT to the whole breast. It would need to control the cancer as well as giving RT to the whole breast does. It would also be important that the PBI gives about the same side effects and breast appearance as treating the whole breast.
We found seven studies, which involved 7586 women. Our evidence is current to May 2015. Local recurrence was rare, but more common with PBI (low‐quality evidence) and the breast appearance (scored by doctors) was worse with PBI (low‐quality evidence). Survival did not differ (high‐quality evidence). Scarring in the breast was worse with PBI (moderate‐quality evidence). The same number of women died of breast cancer with either treatment (moderate‐quality evidence). The same number of women developed spread of breast cancer around their body with either treatment (moderate‐quality evidence). There appeared to be the same number of women who eventually needed the breast removed (mastectomy) after both treatments. Mastectomy could happen because of cancer regrowth in the breast or bad side effects (low‐quality evidence).
This means that at the moment, PBI does not give the same cancer control in the breast as treating the whole breast, but the difference was small. It may cause worse side effects. There are five big ongoing studies that will be important to answer this question. We hope to have a clearer answer in the next update of this review.
