High-dose chemotherapy with hematopoietic stem-cell rescue for high-risk breast cancer.
BACKGROUND
The use of high-dose adjuvant chemotherapy for high-risk primary breast cancer is controversial. We studied its efficacy in patients with 4 to 9 or 10 or more tumor-positive axillary lymph nodes.


METHODS
Patients younger than 56 years of age who had undergone surgery for breast cancer and who had no distant metastases were eligible if they had at least four tumor-positive axillary lymph nodes. Patients in the conventional-dose group received fluorouracil, epirubicin, and cyclophosphamide (FEC) every three weeks for five courses, followed by radiotherapy and tamoxifen. The high-dose treatment was identical, except that high-dose chemotherapy (6 g of cyclophosphamide per square meter of body-surface area, 480 mg of thiotepa per square meter, and 1600 mg of carboplatin per square meter) with autologous peripheral-blood hematopoietic progenitor-cell transplantation replaced the fifth course of FEC.


RESULTS
Of the 885 patients, 442 were assigned to the high-dose group and 443 to the conventional-dose group. After a median follow-up of 57 months, the actuarial 5-year relapse-free survival rates were 59 percent in the conventional-dose group and 65 percent in the high-dose group (hazard ratio for relapse in the high-dose group, 0.83; 95 percent confidence interval, 0.66 to 1.03; P=0.09). In the group with 10 or more positive nodes, the relapse-free survival rates were 51 percent in the conventional-dose group and 61 percent in the high-dose group (P=0.05 by the log-rank test; hazard ratio for relapse, 0.71; 95 percent confidence interval, 0.50 to 1.00).


CONCLUSIONS
High-dose alkylating therapy improves relapse-free survival among patients with stage II or III breast cancer and 10 or more positive axillary lymph nodes. This benefit may be confined to patients with HER-2/neu-negative tumors.
Rodenhuis
Sjoerd
S
Netherlands Cancer Institute, , Department of Medical Oncology, Amsterdam, The Netherlands. sroden@nki.nl
Bontenbal
Marijke
M
Beex
Louk V A M
LV
Wagstaff
John
J
Richel
Dick J
DJ
Nooij
Marianne A
MA
Voest
Emile E
EE
Hupperets
Pierre
P
van Tinteren
Harm
H
Peterse
Hans L
HL
TenVergert
Elisabeth M
EM
de Vries
Elisabeth G E
EG
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D016190:Carboplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000139:chemically induced; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage; D013852:Thiotepa / Q000008:administration & dosage
D018906:Antineoplastic Agents, Alkylating; D013629:Tamoxifen; D003520:Cyclophosphamide; D013852:Thiotepa; D016190:Carboplatin