End points in the analysis of breast cancer survival: relapse versus death from tumor

To determine whether relapse and death from tumor are comparable as survival end points for assessing therapeutic efficacy, five prospective, randomized clinical trials of adjuvant therapy for stage II breast cancer were analyzed. One thousand eight hundred ninety patients were combined from five clinical groups into a single group for analysis.

Actuarial and parametric survival methods were used to generate three estimates for the likelihood of cure (LOC): (1) for all patients, with relapse as the end point to survival (LOCR); (2) for all patients, with death from tumor as the end point (LOCD); and (3) for patients with relapse only with death from tumor as the end point (LOCRD). Linear regression analysis was used to compare time to relapse for each patient with time from relapse to death.

Estimates of LOCR ranged from 33.5% to 38.4%, estimates of LOCD ranged from 36.3% to 44.2%, and estimates of LOCRD ranged from 0% to 6%. Thus LOCR and LOCD are approximately equal for these patients. On the other hand, time to relapse correlated poorly with time from relapse to death (r2 = 0.005).

If therapy affects LOC, relapse and death should ultimately lead to the same conclusion with respect to therapeutic efficacy, because both end points lead to essentially the same LOC. If therapy affects time to relapse, however, these two end points may ultimately lead to different conclusions, because time to relapse correlates poorly with time from relapse to death.