Adjuvant treatment of high-risk stage II breast cancer with doxorubicin followed by high-dose chemotherapy and autologous stem-cell transplantation: a single-institution experience with 132 consecutive patients

• Published in: Bone marrow transplantation (Basingstoke) Vol. 31; no. 8; pp. 655 - 661
• Main Authors: STEMMER, S. M, HARDAN, I, PFEFFER, R. P, BRENNER, H. J, RIZEL, S, RAZ, H, ADAMOU, A. K, INBAR, M, GOTTFRIED, M, MERRICK, Y, COHEN, Y, SULKES, A, BEN-BARUCH, N
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.04.2003
• Subjects: Adjuvant therapy; Adjuvant treatment; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Autografts; Biological and medical sciences; Bone marrow; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer; Cancer therapies; Carboplatin; Carboplatin - administration & dosage; Care and treatment; Chemotherapy; Chemotherapy, Adjuvant; Clinical trials; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Cyclophosphamide; Cyclophosphamide - administration & dosage; Disease-Free Survival; Dosage and administration; Doxorubicin; Doxorubicin - therapeutic use; Drugs; Female; Growth factors; Gynecology. Andrology. Obstetrics; Health aspects; Hematopoietic stem cells; Humans; Lymph nodes; Lymph Nodes - pathology; Lymphatic Metastasis; Lymphatic system; Mammary gland diseases; Medical sciences; Morbidity; Neoplasm Staging; Patient outcomes; Patients; Pharmacology. Drug treatments; Radiation; Radiation therapy; Receptors; Regression analysis; Retrospective Studies; Risk analysis; Risk Factors; Risk groups; Stem cell transplantation; Stem Cell Transplantation - adverse effects; Stem cells; Survival; Survival Analysis; Thiotepa - administration & dosage; Time Factors; Toxicity; Transplantation; Transplantation, Autologous; Tumors; Antineoplastic agent; Toxicity; Stem cell; Adjuvant treatment; Hematopoietic cell; Doxorubicin; Autograft; Isomerases; Graft; Female; Mammary gland; High dose; high-dose chemotherapy; Human; DNA topoisomerase (ATP-hydrolysing); Enzyme; Treatment efficiency; Enzyme inhibitor; breast cancer; Malignant tumor; efficacy; Mammary gland diseases; Antibiotic; Chemotherapy; Treatment; Anthracyclins
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1703856

Several studies have shown conflicting results with the use of intensive consolidation chemotherapy for breast cancer. The aim of the present study was to investigate the efficacy, feasibility and toxicity of high-dose chemotherapy with stem cell support in patients with high-risk stage II breast cancer. From February 1994 to November 1998, 132 consecutive patients with multinode positive breast cancer were entered to the study. In total, 86 patients had >or=10 positive axillary lymph nodes, and 46 had 4-9 positive axillary lymph nodes with at least two additional predetermined risk factors at diagnosis. All patients were offered adjuvant chemotherapy (doxorubicin, 75 mg/m(2) x 4) followed by high-dose chemotherapy (cyclophosphamide 6000 mg/m(2), carboplatin 800 mg/m(2) and thio-tepa 500 mg/m(2)) and autologous stem cell support with growth factor. In all, 131 patients also received local radiation therapy and tamoxifen based on receptor status. After a median follow-up of 51 months (range 27-87), the disease-free and overall survival rates were 72 and 81%, respectively. There was no difference in the outcome for high-risk patients with > or < than 10 positive axillary lymph nodes. On Cox regression analysis only progesterone receptor status was predictive of disease-free, but not overall survival. There were no treatment-related deaths; grades III-IV toxicity was relatively low. This combined approach of doxorubicin followed by high-dose chemotherapy and stem-cell support, followed by locoregional radiotherapy, was safe and seems to be effective in patients with multinode positive stage II breast cancer. In previous trials of adjuvant high-dose therapy in this patient population, treatment-related morbidity and mortality markedly influenced the outcome. For this high-risk patient population, further testing of intensive chemotherapy regimens with a lower toxicity profile is warranted.