Breast cancer: Post-mastectomy radiotherapy: recommended standards

Abstract

The local recurrence rate after mastectomy in breast cancer patients varies significantly in reported series; in some publications from 2% to even more than 50% at 10 years. The reasons for these differences can be found in patient selection and the surgical method and technical skills of the surgeon. For example, a low recurrence percentage can be obtained by combining a good surgical procedure with the exclusion of patients for radical mastectomy by following strict inoperability criteria. For this purpose, the following criteria are often used: fixation of the tumour and/or lymph nodes to the chest wall, inflammatory breast cancer, and in some institutes a positive axillary apex biopsy. In 1949 Ralston Paterson and colleagues in Manchester started probably the first randomized clinical trial in the world investigating the potential of radiotherapy in improving local control and indirectly survival [1]. They randomized patients after mastectomy between no radiotherapy and post-mastectomy radiotherapy. For this purpose 1461 patients were entered in this trial. He and his colleagues demonstrated that radiotherapy was able to reduce significantly the amount of local recurrences thereby preventing patients dying from symptoms of uncontrolled local disease. Unfortunately long term follow up showed that the potential gain in survival was diminished by an excess of radiotherapy-related cardiovascular complications. It would be unfair to criticize the trial design according to current standards and the radiation technique used but a few remarks should be made here. For example, the randomization was based on the patient's date of birth (odd or even), so the surgeon would know beforehand in which arm the patient would be randomized. He may have therefore decided not to select patients for the trial if they had a high risk of local recurrence knowing that they would be randomized to no further treatment. Instead he may have referred these patients for radiotherapy, leading to unbalanced treatment arms. The major reason for the excess of cardiovascular deaths seen in this trial was the equipment available at that time. The patients were treated with orthovoltage equipment using a technique that delivered a high dose to a large part of the heart with higher fraction doses. A reduction of the local recurrence rate, by a factor of 0.6, by post-mastectomy radiotherapy has now been confirmed by many trials. It took until recently for it to be demonstrated that improvement in local control could result in about 10% improved survival rate [2-4]. These results became available with the publication of the long term follow up data from a few major trials started after 1975. These trials have shown a gain that can be reached by careful selection of high-risk patients for radiotherapy and through the execution of meticulous radiotherapy techniques, avoiding over dosage of radiation to the heart. The impact of improved local control on the survival rate shown by these trials suggests that distant metastases may arise from recurrent local disease, stressing the need for adequate local treatment.