Long-term follow-up of the first breast conservation trial: Guy' wide excision study.

Breast conservation therapy is now accepted as a proven approach for selected patients with operable breast cancer. Nevertheless, it is important to appreciate that the first randomized trials, which were carried out at Guy's Hospital, indicated the need for good local control and the increased mortality from breast cancer which occurred when treatment was sub-optimal. In the first trial 374 women aged > or = 50, with T1, T2, N0 and N1 tumours were randomized to either Halsted mastectomy and postoperative radiotherapy or wide excision and postoperative irradiation. Both groups were given 25-27 Gy to the gland fields and the wide excision group received additionally 35-38 Gy to the breast. Hence the wide excision group had no axillary surgery and subsequent axillary irradiation using what is now regarded as a low dose of radiotherapy. After 25 years, local relapse has occurred in 26% of the mastectomy group and 50% of the wide excision group (chi(2)= 21.6, P < 0.001). The breast cancer mortality rate at 25 years was 56% in the mastectomy group and 63% in those treated by wide excision (chi(2)= 5.33, P= 0.02). The first analysis of this trial indicated that increased risk of axillary relapse was restricted to N1 cases and so a second trial was conducted with entry only for those with clinically negative axillae (N0 series). Of 255 cases entered, 133 were randomized to mastectomy and 122 to wide excision. The same radiotherapy schedule was used as in the original Series. After 25 years local relapse occurred in 18% of the mastectomy cases and 54% of the wide excision group (chi(2)= 30.6, P < 0.001). There were significantly more distant relapse in the latter group (chi(2)= 6.32, P= 0.01), and a significant increase in breast cancer deaths (57% versus 44%, chi(2)= 4.27, P= 0.04). These two trials, conducted before the widespread introduction of systemic adjuvant therapy, both indicate the long-term effects of inadequate primary treatment. Inadvertent failure to treat the axilla effectively led not only to significantly increased axillary relapse rates but also to more deaths from metastatic disease.

RCT Entities:   Population Interventions Outcomes