Stage III and oestrogen receptor negativity are associated with poor prognosis after adjuvant high-dose therapy in high-risk breast cancer

We report on the efficacy and toxicity of a sequential high-dose therapy wi th peripheral blood stem cell (PBSC) support in 85 patients with high-risk stage II/III breast cancer. There were 71 patients with more than nine tumo ur-positive axillary lymph nodes. An induction therapy of two cycles of ifo sfamide (total dose, 7.5 g m(-2)) and epirubicin (120 mg m-2) was given, an d PBSC were harvested during G-CSF-supported leucocyte recovery following t he second cycle. The PBSC-supporied high-dose chemotherapy consisted of two cycles of ifosfamide (total dose, 12 000 mg m(-2)), carboplatin (900 mg m- 2) and epirubicin (180 mg m(-2)). Patients were autografted with a median n umber of 3.7 x 10(6) CD34+ cells kg(-1) (range, 1.9-26.5 x 10(6)) resulting in haematological reconstitution within approximately 2 weeks following hi gh-dose therapy. The toxicity was moderate in general, and there was no tre atment-related toxic death. Twenty-one patients relapsed between 3 and 30 m onths following the last cycle of high-dose therapy (median, 11 months). Th e probability of disease-free and overall survival at 4 years were 60% and 83%, respectively. According to a multivariate analysis, patients with stag e II disease had a significantly better probability of disease-free surviva l (74%) in comparison to patients with stage III disease (36%). The probabi lity of disease-free survival was also significantly better for patients wi th oestrogen receptor-positive tumours (70%) compared to patients with rece ptor-negative ones (40%), Bone marrow samples collected from 52 patients af ter high-dose therapy were examined to evaluate the prognostic relevance of isolated tumour cells. The proportion of patients presenting with tumour c ell-positive samples did not change in comparison to that observed before h igh-dose therapy (65% vs 71%), but a decrease in the incidence and concentr ation of tumour cells was observed over time after high-dose therapy. This finding was true for patients with relapse and for those in remission, whic h argues against a prognostic significance of isolated tumour cells in bone marrow. In conclusion, sequential high-dose chemotherapy with PBSC support can be safely administered to patients with high-risk stage II/III breast cancer. Further intensification of the therapy, including the addition of n on-cross resistant drugs or immunological approaches such as the use of ant ibodies against HER-2/NEU, may be envisaged for patients with stage ill dis ease and hormone receptor-negative tumours.