Morbidity Related to Axillary Irradiation in the Treatment of Breast Cancer

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Abstract
Some of the most debilitating morbidity after surgery and radiotherapy for breast cancer is related to treatment of the axilla. This includes persistent arm lymphoedema, impaired shoulder mobility and brachial plexopathy. Considerable research efforts have been carried out on the radiation pathogenesis and the clinical radiobiology of these clinical endpoints, which has enabled their severity and incidence to be minimized. It is clear that the radiation dose-response relationships for these late endpoints are very steep. In other words, even small changes in the exact dose fractionation and physical dose distribution can cause major changes in toxicity. In particular, in many treatment schedules dose fractions larger than 2 Gy have been used without a sufficient reduction in total dose to avoid increased late effects. This is important, as much of the available literature reports side effects after suboptimal dose-fractionation schedules and inferior radiotherapy techniques. Such reports are not representative of what can be achieved using modern radiotherapy. An interesting parallelism to the problems encountered in reviewing historical experience is found in the British breast litigation, the current status of which is presented in this article. Furthermore, morbidity after radiotherapy is strongly influenced by concomitant surgery and/or chemotherapy, and this should be allowed for when designing the overall treatment. Apart from other therapeutic modalities, it has been suggested that other exogenous factors have an influence on the risk of radiotherapy-related morbidity. However, patients' age and, in the case of lymphoedema, also obesity are the only factors that have been established with some certainty. Routine adjustment of radiotherapy dose in these cases is not recommended. Two current developments may strengthen the role of radiotherapy in the treatment of breast cancer. Sentinel node biopsy may allow nodal staging without major surgical excision of axillary nodes and this opens the possibility for a more optimal combination of radiotherapy and surgery in the management of the axilla. With more cancers now being detected by systematic screening programmes, this will also increase the possibilities for conservative management, which in most cases involves radiotherapy. In conclusion, the improved understanding of the clinical radiobiology of late sequelae after radiotherapy allows treatment schedules and techniques to be devised that are therapeutically effective while maintaining a minimal risk of serious, late morbidity.