The United Kingdom has one of the highest incidences of breast cancer (123 per 100,000 women were diagnosed with breast cancer in 2005) and has historically been home to pioneers of breast cancer treatments.
Without being exhaustive, the trials originating in the United Kingdom over the last century have contributed significantly to improving our understanding about breast cancer and changed practice worldwide. Many of these trials have a story behind them that illustrates how conceptual leaps essential for progress in medicine are taken. The current TARGIT (TARGeted Intraoperative radioTherapy) trial is a story that will be highlighted because it demonstrates the interweaving of various new concepts in the evolution of local treatment of breast cancer.
Radical curative surgery for breast cancer was championed by William Halsted in North America and H. Sampson Handley and Gordon-Taylor in the United Kingdom and Europe. David Patey, working in the Middlesex Hospital in London, was one of the first to suggest in 1948 that removal of the pectoralis muscle was not necessary and that local treatment of breast cancer could be achieved without undue morbidity.1 Several trials were conducted in the latter half of the 20th century including many from the United Kingdom. The number of patients in these trials was small and the concept of statistical power was ill understood. Consequently, although these trials of local therapy demonstrated how the benefit of radiotherapy was a clear reduction in local recurrence rate by two-thirds, most of these trials did not show any survival advantage, thus apparently supporting the Fisher hypothesis that local control does not in any way influence distant disease. This concept was challenged only because of 2 events—the amalgamation of all trial data so the number of patients was adequate, and the longer follow-up that was almost necessitated by the continuing presence of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG). It was the efforts of EBCTCG's review of randomized previously performed trials that has now conclusively demonstrated that local control influences distant disease, although the puzzle remains why this effect is only modest.
The psychological impact of breast cancer diagnosis and its treatment was long neglected and the studies in the United Kingdom were perhaps pioneering in terms of elucidating the psychological and social effects of a mastectomy compared with breast-conserving surgery, or more recently, axillary clearance compared with sentinel node biopsy.2-4
The low sensitivity of clinical examination or any other imaging modality to accurately screen out the negative axilla meant that many patients were having their uninvolved axillary tissue excised unnecessarily along with its posttraumatic morbidity such as lymphedema, numbness, and shoulder restriction. This was demonstrated with a high level of objective evidence by the Edinburgh group,5 which also championed the concept of a formal 4-node axillary lymph node sampling. In their hands there was no false negative sample and the randomized trial confirmed that the procedure was safe and effective.6-8...