Previous randomised trials have shown that prolonged chemotherapy for breast cancer substantially reduces the risk of disease relapse and death compared with no chemotherapy. However, toxic side-effects are a concern because they may result in decreased quality of life for patients; it is therefore important to determine whether the benefits of chemotherapy are sufficient to offset its side effects and justify its use, both overall, and within specific subgroups of patients.
Bernard Cole from Dartmouth Medical School, Lebanon, USA, and colleagues did a statistical analysis, using data from 47 randomised trials involving about 18,000 women, to measure the benefits of chemotherapy in terms of survival time adjusted for the quality of life experienced. The investigators used a statistical method called Q-TWiST (Quality-adjusted Time Without Symptoms of disease or Toxicity of treatment) to compare women treated with chemotherapy with women not given chemotherapy. Their analysis considered three major health states experienced by patients: (1) time with chemotherapy, (2) time following chemotherapy and before disease relapse, and (3) time following disease relapse. They weighted the duration of each health state based on a valuation of quality of life, and summed the weighted durations to produce a measure called quality-adjusted survival.
Within 10 years' follow-up the benefit of increased relapse-free and overall survival for younger women (aged younger than 50 years) who received chemotherapy balanced the burdens in terms of acute toxic side-effects, especially among women enrolled in trials that did not include tamoxifen treatment. 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 compared with the no-chemotherapy group. Chemotherapy provided more quality-adjusted time than control for most quality-of-life valuations assigned to time spent undergoing chemotherapy and time after relapse. The range of the quality-adjusted benefit was 0.6 months to 10.3 months. For older women (50-69 years) overall, chemotherapy also provided substantial benefit compared with no chemotherapy, but the size of the benefit was less than that seen in younger women. Average gains within 10 years for older women treated with chemotherapy were 6.8 months of relapse-free survival and 2.9 months of overall survival. The quality-adjusted benefit ranged from 3.1 to 6.8 months. For older women with oestrogen-receptor-poor tumours who did not receive tamoxifen (9% of the total), the quality-adjusted benefit of chemotherapy was significant and similar to younger women.
Bernard Cole comments: "We conclude that within 10 years' follow-up the benefits of adjuvant chemotherapy outweigh its burdens for younger women for a wide range of quality-of-life values for toxicity and relapse. However, the size of the benefit will depend on these values. Therefore additional studies to evaluate quality of life relative to chemotherapy, endocrine therapies, and their combination are essential. In addition, very few younger women were enrolled in studies designed to evaluate the role of chemotherapy plus endocrine therapy (ovarian ablation or tamoxifen) compared with endocrine therapy alone. Such trials for younger women with tumours that express steroid-hormone receptors should be a high priority."
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Contact: Dr Bernard Cole, Dartmouth Medical School. 7927 Rubin Building, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756, USA; T) 1-603-650-7247; F) 1-603-650-6485; E) firstname.lastname@example.org