In metastatic breast cancer tumour markers’ increase predicts, by a few months (lead time) disease progression. In breast cancer patients with endocrine dependent metastatic disease, we reported a prolonged clinical benefit and overall survival when first line conventional antiestrogen hormone therapy was started at the lead time and also when an immunotherapy schedule was added to the same conventional hormone treatment. Thirty-two of these last patients were considered (group a). In 27 (group b) of these 32 patients who progressed during first line salvage hormone plus immunotherapy the lead time at the progression of metastatic disease during therapy was compared with that at the onset of metastases when the same patients were without treatment and with that of a control group (group c) who did not receive immunotherapy. At disease progression, CEA–TPA–CA15.3 sensitivity was 92.5% in the group b (studied patients) and 88.5% in the group c (controls). At the progression in the group b, CEA–TPA–CA15.3 lead time (m ± sd, months) was significantly longer than in group c (12.1 ± 12.9 vs 2.4 ± 4.0) ( P = 0.000). Besides, in group b the lead time was significantly longer at the progression than at the metastatic onset ( P = 0.003) while in the group c the difference was near to significance ( P = 0.05). The CEA–TPA–CA15.3 tumour marker panel accurately predicted metastatic disease progression and immunotherapy significantly prolonged the CEA–TPA–CA15.3 lead time. This can be used for anticipating salvage treatment in these patients.