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 with 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 tumour-positive axillary lymph nodes. An induction therapy of two cycles of ifosfamide (total dose, 7.5 g m(-2)) and epirubicin (120 mg m(-2)) was given, and PBSC were harvested during G-CSF-supported leucocyte recovery following the second cycle. The PBSC-supported 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 number 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 high-dose therapy. The toxicity was moderate in general, and there was no treatment-related toxic death. Twenty-one patients relapsed between 3 and 30 months following the last cycle of high-dose therapy (median, 11 months). The probability of disease-free and overall survival at 4 years were 60% and 83%, respectively. According to a multivariate analysis, patients with stage II disease had a significantly better probability of disease-free survival (74%) in comparison to patients with stage III disease (36%). The probability of disease-free survival was also significantly better for patients with oestrogen receptor-positive tumours (70%) compared to patients with receptor-negative ones (40%). Bone marrow samples collected from 52 patients after high-dose therapy were examined to evaluate the prognostic relevance of isolated tumour cells. The proportion of patients presenting with tumour cell-positive samples did not change in comparison to that observed before high-dose therapy (65% vs 71%), but a decrease in the incidence and concentration of tumour cells was observed over time after high-dose therapy. This finding was true for patients with relapse and for those in remission, which 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 non-cross resistant drugs or immunological approaches such as the use of antibodies against HER-2/NEU, may be envisaged for patients with stage III disease and hormone receptor-negative tumours.
Hohaus
S
S
Department of Internal Medicine V, University of Heidelberg, Germany.
Funk
L
L
Martin
S
S
Schlenk
R F
RF
Abdallah
A
A
Hahn
U
U
Egerer
G
G
Goldschmidt
H
H
Schneeweiss
A
A
Fersis
N
N
Kaul
S
S
Wallwiener
D
D
Bastert
G
G
Haas
R
R
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019046:Bone Marrow Neoplasms / Q000188:drug therapy / Q000556:secondary; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy / Q000601:surgery; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D015080:Mesna / Q000008:administration & dosage; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis*; D011994:Recombinant Proteins; D013629:Tamoxifen / Q000008:administration & dosage; D016896:Treatment Outcome
D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D013629:Tamoxifen; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D016190:Carboplatin; D015080:Mesna; D000069585:Filgrastim; D007069:Ifosfamide