Polychemotherapy for early breast cancer: an overview of the randomised clinical trials with quality-adjusted survival analysis

Background Overview analysis involving 18 000 women with breast cancer in 4 7 randomised trials showed that prolonged chemotherapy significantly reduce s the risk of relapse and death compared with no chemotherapy. Here we expr ess the size of the benefit in terms of quality-adjusted survival time gain ed. Methods We used the Q-TWIST method (Quality-adjusted Time Without Symptoms of disease and Toxicity of treatment) to provide treatment comparisons with in 10 years' follow-up, incorporating differences in quality of life associ ated with times patients spend with chemotherapy toxic effects, after relap se, and without symptoms of relapse or toxicity. Findings Within 10 years' follow-up the benefit of increased relapse-free a nd overall survival for younger women (<50 years old) who received polychem otherapy balanced the burdens in terms of acute toxic side-effects, especia lly among women enrolled in trials that did not include tamoxifen. Overall, chemotherapy-treated younger women gained an average of 10.3 months of rel apse-free survival and 5.4 months of overall survival within 10 years (p<0. 0001 for both) compared with the no-chemotherapy group. Polychemotherapy pr ovided more quality-adjusted time than control across nearly all values of utility weights for time spent undergoing chemotherapy and time after relap se. The range of benefit was from -0.6 to 10.3 months. For older women (50- 69 years) overall, polychemotherapy also provided significant benefit compa red with no chemotherapy but, compared with younger women, the size of bene fit was less and the range of utility-weight values favouring polychemother apy was smaller. Average gains for older women treated with polychemotherap y (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 r ange of quality-adjusted benefit was -3.1 to 6.8 months. For older women wi th oestrogen-receptor-poor tumours who did not receive tamoxifen (9% of the total), the benefit of polychemotherapy was significant and similar to tha t observed for younger women. Interpretation The benefits of adjuvant chemotherapy within 10 years outwei gh 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 end ocrine therapy alone are required for younger patients with tumours that ex press steroid-hormone receptors.