Adjuvant chemotherapy for premenopausal breast cancer: a meta-analysis using quality-adjusted survival.
OBJECTIVE
Adjuvant chemotherapy for early breast cancer has been shown to offer an improvement in recurrence-free and overall survival, especially for younger women, but the acute toxic effects of this treatment discourage some physicians from prescribing it. The purpose of this analysis was to determine whether the benefit of 6 months of adjuvant CMF (cyclophosphamide, methotrexate, fluorouracil) treatment outweighs its costs in terms of toxic effects.


METHODS
A meta-analysis of quality-adjusted survival was performed based on data from 1229 patients, aged 49 years or younger, randomized in eight trials comparing CMF versus no adjuvant systemic therapy. The eight trials were included in the worldwide overview conducted by the Early Breast Cancer Trialists' Collaborative Group. The Q-TWiST method was used in a meta-analysis that provided treatment comparisons incorporating differences in quality of life associated with the amount of time patients spend with subjective toxic effects, after relapse, and without symptoms of relapse.


RESULTS
Within 6 years of follow-up evaluation for patients with node-positive disease, the benefit in terms of increased relapse-free and overall survival balanced the costs in terms of acute toxic side effects. This was true even for the extreme case in which a zero value was assigned to all 6 months during which patients might receive adjuvant CMF chemotherapy. Within 10 years of follow-up evaluation, treated patients gained an average of 1.5 years of relapse-free survival time, almost 1 year of overall survival time, and 1 year of time without symptoms and toxicity.


CONCLUSIONS
Adjuvant chemotherapy for younger women with node-positive breast cancer provided substantial amounts of quality-adjusted survival time, even after accounting for costs associated with toxic effects of the treatment. The Q-TWiST method represents a valuable tool for comparing treatments because it incorporates patients' perceptions of their quality of life for therapeutic decision-making.
Gelber
R D
RD
Division of Biostatistics, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Cole
B F
BF
Goldhirsch
A
A
Bonadonna
G
G
Howell
A
A
McArdle
C S
CS
Mouridsen
H T
HT
Rubens
R D
RD
Welvaart
K
K
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D017697:Premenopause; D019057:Quality-Adjusted Life Years; D015996:Survival Rate; D016896:Treatment Outcome
D003520:Cyclophosphamide; D005472:Fluorouracil; D008727:Methotrexate