High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer.
BACKGROUND
There is a hypothesis that high dose chemotherapy with autologous bone marrow or peripheral stem cell transplantation (autograft) may improve survival for women with metastatic breast cancer.


OBJECTIVE
To compare the effectiveness of high dose chemotherapy and autologous bone marrow or stem cell transplantation with conventional chemotherapy for women with metastatic breast cancer.


METHODS
We used the Cochrane Breast Cancer Group search strategy, adding these terms: bone marrow transplantation, stem cell transplantation, autologous stem cell support. The following databases were searched: MEDLINE (until November 2004), EMBASE (until November 2004), ASCO (American Society of Clinical Oncology) (1995-2004) and the COCHRANE LIBRARY (Issue 4 2004). We searched the Cochrane Breast Cancer Group database and cooperative research groups' websites for unpublished trials.


METHODS
Randomised controlled trials comparing the effectiveness of high dose chemotherapy and autograft with conventional chemotherapy for women with metastatic breast cancer. Studies included one or more of the following outcomes: treatment related mortality, overall or progression-free survival at 1, 2, 3, 5 or 7 years, morbidity, quality of life measures, time to tumour progression, overall survival time.


METHODS
Six randomised controlled trials met the inclusion criteria. Two independent reviewers extracted data.


RESULTS
In total 438 eligible women were randomised to receive high dose chemotherapy with autograft and 412 were randomised to receive conventional treatment. There were fifteen treatment-related deaths among the high dose group and two in the control (conventional dose) group (RR 4.07 (95% CI 1.39, 11.88)). There was no statistically significant difference in overall survival between the high dose and control groups at one year, three years or five years. At one and five years of follow up, there was a statistically significant difference in event-free survival, favouring the high dose group (one year: RR 1.76 (95% CI 1.40, 2.21); five years: RR 2.84 (95% CI 1.07, 7.50). Toxicity was more severe in the high dose group. Only one of the trials has followed up all women for five years and further data are awaited.


CONCLUSIONS
Although there is statistically significant evidence that high dose chemotherapy and autograft improves event free survival compared to conventional chemotherapy, there is no statistically significant evidence of benefit in overall survival for women with metastatic breast cancer. High dose chemotherapy with bone marrow or stem cell transplantation should not be given to women with metastatic breast cancer outside of clinical trials.
Farquhar
C
C
Obstetrics & Gynaecology, National Women's Hospital, Private Bag 92019, University of Auckland, Auckland, New Zealand, 1003. c.farquhar@auckland.ac.nz
Marjoribanks
J
J
Basser
R
R
Hetrick
S
S
Lethaby
A
A
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D033581:Stem Cell Transplantation; D013629:Tamoxifen / Q000008:administration & dosage; D014182:Transplantation, Autologous
D013629:Tamoxifen