The impact of radiotherapy on trials of axillary management in early breast cancer.

The presence of metastatic disease in the axillary lymph nodes is one of the most important prognostic factors in early breast cancer1-3 but the management of the clinically and radiologically negative axilla (cN0) with positive nodes following sentinel lymph node biopsy (SLNB) is still a matter of debate. The presence of nodal macrometastases (>2mm) is often regarded as an indication for axillary lymph node dissection (ALND)4 but randomised studies have reported no benefit for ALND in terms of locoregional recurrence (LRR) or survival with a significant risk of long term arm lymphoedema5. As a consequence, many centres offer axillary radiotherapy (ART) but as to whether this is required in patient with low burden axillary disease (1-2 involved nodes) is still debatable. Surgery and radiotherapy (RT) have both demonstrated effectiveness as loco-regional therapies in breast cancer but without accurate assessment of radiation doses and targets in surgical trials of the axilla, results from randomised controlled trials (RCTs) become ambiguous. A lack of robust Radiotherapy Quality Assurance (RTQA) has contributed to variable practice and the oncology community has waited for over a decade for confirmatory trials delaying implementation of potentially clinically relevant results. This review article discusses the main RCTs conducted to determine the oncological safety of reduced axillary surgery with an emphasis on the influence of RT on trial conduct, endpoints and conclusions.