Results
Of the 1006 breast cancer patients screened, 155 (15%) had autoantibodies to p53 in the most recently obtained plasma sample. Of the total patient cohort, the disease status corresponding to the time of collection of this sample was known in 960 patients. Autoantibody status was compared with disease status (Table 1). There was no correlation with those patient groups who had known active disease (either continuous active, or recurrent) or with those in primary or secondary clinical remission; the incidence of p53 autoantibody positivity was approximately 16% in all groups. The possibility that patient age may influence humoral immunity was tested by comparing premenopausal with postmenopausal patients; there was no correlation with the patients' menopausal status at diagnosis with autoantibodies to p53 (Table 2).
For those patients whose most recent sample contained p53 autoantibodies, all previous samples were screened. This longitudinal review showed that autoantibody tended to be persistent. Although preoperative plasma samples were not available, some patients had been included in this study from the time of their first appointment at the oncology clinic; these samples were those that were most likely to contain any residual p53 autoantibody associated with the primary tumour. For those who had antibody present at early follow up, levels tended to persist throughout follow up. This was in contrast to those patients who had no autoantibody detectable within 30 days of surgery (see below). Overall, any fluctuations in autoantibody levels within the positive patient cohort gave no consistent pattern when compared with the clinical history of each patient. Although there was no correlation between p53 autoantibody status and disease behaviour, in one patient there was a strong correlation with prednisolone therapy and a fall in p53 autoantibodies, presumably as a result of steroid-induced immunosuppression. Shortly after steroid treatment, the patient developed cerebral metastases which were marked by a rapid rise in CA15.3.
Of the 851 patients who were negative for p53 autoantibodies at a 1/10 plasma dilution, 60 had had a plasma sample taken within 30 days of diagnosis of breast cancer. Of these, 22 had current active disease and 38 had current inactive disease, at the time when the autoantibody status of all 60 patients was negative. The first sample (taken less than 30 days after diagnosis) was screened and showed that 59 out of the 60 proved to have also been negative for p53 autoantibodies around the time of diagnosis (Table 3). This suggests that, if a patient is negative for p53 autoantibodies at diagnosis of active primary disease, then that patient is highly unlikely to develop humoral immunity to p53, even in the presence of recurrent disease.