Abstract
BackgroundRadiotherapy (RT) improves overall survival (OS) of breast cancer patients after breast conserving surgery and after mastectomy in patients with involved lymph nodes (LN). The contribution of RT to the regional LN to this survival benefit was poorly understood. Recently, the results of three large randomized trials addressing this question have become available.Material and methodsThe published abstracts (full publication pending) of the MA.20 (n=1832) and the EORTC 22922–10925 (EORTC) (n=4004) trial and the full publication of the French trial (n=1334) were basis of the meta-analysis. Main eligibility criteria were positive axillary LN (all trials), LN negative disease with high risk for recurrence (MA.20), and medial/central tumor location (French, EORTC). The MA.20 and the EORTC trial tested the effect of additional regional RT to the internal mammary (IM) LN and medial supraclavicular (MS) LN, whereas in the French trial all patients received RT to the MS-LN and solely RT to the IM-LN was randomized. Primary endpoint was OS. Secondary endpoints were disease-free survival (DFS) and distant metastasis free survival (DMFS).ResultsRegional RT of the MS-LN and the IM-LN (MA.20 and EORTC) resulted in a significant improvement of OS (Hazard Ratio (HR) 0.85 (95% CL 0.75 - 0.96)). Adding the results of the French trial and using the random effects model to respect the different design of the French trial, the effect on OS of regional radiotherapy was still significant (HR 0.88 (95% CL 0.80 - 0.97)). The absolute benefits in OS were 1.6% in the MA.20 trial at 5 years, 1.6% in the EORTC trial at 10 years, and 3.3% in the French trial at 10 years (not significant in single trials). Regional radiotherapy of the MS-LN and the IM-LN (MA.20 and EORTC) was associated with a significant improvement of DFS (HR 0.85 (95% CL 0.77 - 0.94)) and DMFS (HR 0.82 (95% CL 0.73 - 0.92)). The effect sizes were not significantly different between trials for any end point.ConclusionAdditional regional radiotherapy to the internal mammary and medial supraclavicular lymph nodes statistically significantly improves DFS, DMFS, and overall survival in stage I-III breast cancer.
Highlights
Clinical data indicate that breast cancer is a radiosensitive disease
Adding the results of the French trial and using the random effects model to respect the different design of the French trial, the effect on overall survival (OS) of regional radiotherapy was still significant (HR 0.88 (95% CL 0.80 - 0.97))
In their randomized trial (n = 737) that tested the resection of IM-lymph nodes (LN) in addition to mastectomy and axillary surgery, no survival benefit of the extended surgical approach was shown in spite of the fact that pathological involvement of the internal mammary LN was confirmed in 21% of patients
Summary
Clinical data indicate that breast cancer is a radiosensitive disease. Adjuvant radiotherapy after breast-conserving surgery reduces the risk of ipsilateral in breast recurrence by at least a factor of 3 and halves the risk of any disease recurrence resulting in a significantly improved overall survival [1,2]. Radiotherapy after mastectomy in node positive breast cancer patients reduces chest wall recurrences by a factor 3–4 and improves overall survival by 6% [3]. The work published by Veronesi and colleagues [6] that was done before any systemic treatment of breast cancer had been established, can be interpreted in the same direction. In their randomized trial (n = 737) that tested the resection of IM-LN in addition to mastectomy and axillary surgery, no survival benefit of the extended surgical approach was shown in spite of the fact that pathological involvement of the internal mammary LN was confirmed in 21% of patients. The results of three large randomized trials addressing this question have become available
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