title: Polychemotherapy for early breast cancer: an overview of the randomised clinical trials with quality-adjusted survival analysis.
abstract: BACKGROUND
  Overview analysis involving 18000 women with breast cancer in 47 randomised trials showed that prolonged chemotherapy significantly reduces the risk of relapse and death compared with no chemotherapy. Here we express the size of the benefit in terms of quality-adjusted survival time gained.
  
  
  METHODS
  We used the Q-TWiST method (Quality-adjusted Time Without Symptoms of disease and Toxicity of treatment) to provide treatment comparisons within 10 years' follow-up, incorporating differences in quality of life associated with times patients spend with chemotherapy toxic effects, after relapse, and without symptoms of relapse or toxicity.
  
  
  RESULTS
  Within 10 years' follow-up the benefit of increased relapse-free and overall survival for younger women (<50 years old) who received polychemotherapy balanced the burdens in terms of acute toxic side-effects, especially among women enrolled in trials that did not include tamoxifen. Overall, chemotherapy-treated younger women gained an average of 10.3 months of relapse-free survival and 5.4 months of overall survival within 10 years (p<0.0001 for both) compared with the no-chemotherapy group. Polychemotherapy provided more quality-adjusted time than control across nearly all values of utility weights for time spent undergoing chemotherapy and time after relapse. The range of benefit was from -0.6 to 10.3 months. For older women (50-69 years) overall, polychemotherapy also provided significant benefit compared with no chemotherapy but, compared with younger women, the size of benefit was less and the range of utility-weight values favouring polychemotherapy was smaller. Average gains for older women treated with polychemotherapy (with or without tamoxifen) were 6.8 months of relapse-free survival (p<0.0001) and 2.9 months of overall survival (p=0.0001) within 10 years. The range of quality-adjusted benefit was -3.1 to 6.8 months. For older women with oestrogen-receptor-poor tumours who did not receive tamoxifen (9% of the total), the benefit of polychemotherapy was significant and similar to that observed for younger women.
  
  
  CONCLUSIONS
  The benefits of adjuvant chemotherapy within 10 years outweigh the burdens especially for younger women (<50 years old) and among older women (50-69 years) to a lesser degree. Additional studies to compare the quality-adjusted survival of chemotherapy plus endocrine therapy versus endocrine therapy alone are required for younger patients with tumours that express steroid-hormone receptors.
authors.affiliation: Dartmouth College Medical School, Lebanon, NH, USA. bernard.cole@dartmouth.edu
authors.forename: B F
authors.initials: BF
authors.lastname: Cole
authors.forename: R D
authors.initials: RD
authors.lastname: Gelber
authors.forename: S
authors.initials: S
authors.lastname: Gelber
authors.forename: A S
authors.initials: AS
authors.lastname: Coates
authors.forename: A
authors.initials: A
authors.lastname: Goldhirsch
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D019057:Quality-Adjusted Life Years; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D013629:Tamoxifen