High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer.
BACKGROUND
Overall survival rates are disappointing for women with early poor prognosis breast cancer. Autologous transplantation of bone marrow or peripheral stem cells (in which the patient is both donor and recipient) has been considered a promising technique because it allows much higher doses of chemotherapy to be used.


OBJECTIVE
To compare the effectiveness of high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer. Outcomes were survival rates, toxicity and quality of life.


METHODS
We searched the Cochrane Breast Cancer Group specialised register, The Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2004), MEDLINE (1966 to November 2004), EMBASE (1980 to November 2004), PsycINFO (1984 to November 2004), Cinahl (1982 to November 2004), web sites of co-operative research groups and ASCO (American Society of Clinical Oncologists) and reference lists of articles found.


METHODS
Randomised controlled trials comparing high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer.


METHODS
Fifteen trials were considered. Thirteen were included and two were excluded. Three independent reviewers extracted data.


RESULTS
Analysis included 2535 women randomised to receive high dose chemotherapy with autograft and 2529 randomised to receive conventional chemotherapy. There were 65 treatment-related deaths on the high dose arm and four on the conventional dose arm (RR 8.58 (95% CI 4.13, 17.80). Many studies have not completed follow-up and have reported only preliminary results. There was a statistically significant benefit in event-free survival for women in the high dose group at three years (RR 1.12 (95% CI 1.06, 1.19)) and at four years (RR 1.30 (95% CI 1.16, 1.45)). At five and six years there was no statistically significant difference between the groups in event-free survival. With respect to overall survival, there was no statistically significant difference between the groups at any stage of follow up. Morbidity was more common and more severe in the high dose group. However there was no statistically significant difference between the groups with respect to the incidence of second cancers at five to seven years' follow up. Women in the high dose group reported significantly worse quality of life scores immediately after treatment, but few statistically significant differences were found between the groups by one year.


CONCLUSIONS
There is insufficient evidence to support the routine use of high dose chemotherapy with autograft for women with early poor prognosis breast cancer.
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
Lethaby
A
A
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016026:Bone Marrow Transplantation; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D033581:Stem Cell Transplantation; D015996:Survival Rate; D014182:Transplantation, Autologous