A systematic overview of chemotherapy effects in breast cancer

A systematic review of chemotherapy trials in several tumour types was perf ormed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are describ ed separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literatu re on chemotherapy for breast cancer is based on 233 randomised studies, 9 meta-analysis of randomised studies. a population-based cohort study and 18 overviews/retrospective analyses including a total of 155 243 patients. Th e conclusions reached can be summarised into the following points: Adjuvant treatment There is solid scientific support from randomised studies that adjuvant pol ychemotherapy at 10 years will result in an absolute mortality reduction fo r patients younger than 50 years by 12% for node positive (34% relative mor tality reduction corresponding to an estimated median survival prolongation of several years) and 6% for node negative patients. For women aged 50 to 69 years, the corresponding figures for node positive and node negative pat ients are 6% and 2%,. respectively (approximately 11% relative mortality re duction). Anthracycline-containing combinations result in an absolute survival benefi t at five years of 3% compared with non-anthracycline based polychemotherap y. There are indications that the taxane paclitaxel may further improve the su rvival compared with anthracyclines. However, the limited data preclude con clusions for the routine care. The addition of tamoxifen to chemotherapy further enhances the survival ben efit for receptor positive subgroups. The roles of more dose-intensive regimens, including high-dose therapy with stem cell support, are presently studied in randomised investigations. The data presented so far are conflicting but they do not in general support h igh-dose therapy. Quality of life. based on analyses of randomised studies, demonstrate that adjuvant polychemotherapy has an initial detrimental effect, but long-term follow-up of treated patients demonstrates no impairment of quality of life compared with untreated patients. Polychemotherapy in standard doses should be offered to premenopausal node positive patients, and the corresponding post menopausal group with a recep tor-negative breast cancer and to node negative patients with high risk fac tors. Polychemotherapy should be combined with tamoxifen to all patients wi th receptor-positive tumours. Due to a need of more knowledge in this field . patients should be included in investigational protocols. Locally advanced breast cancer Based on current knowledge, treatment of patients with locally advanced bre ast cancer should include neoadjuvant/preoperative polychemotherapy since t here is evidence from controlled studies that such therapy will statistical ly significantly increase the number of patients who can be offered breast- conserving surgery. Indirect comparisons also demonstrate survival improvem ents, but the scientific support is equivocal. Metastatic breast cancer The median survival for patients with metastatic disease treated with conve ntional chemotherapy doses and regimens is 12 to 24 months. Retrospective cohort studies indicate that the use of non-anthracycline con taining chemotherapy compared with no chemotherapy might add a survival gai n of six to nine months. However. this estimation is based on equivocal dat a. Based on overview data, polychemotherapy results in a statistically signifi cant survival gain compared with single-agent therapy. Based on repeated randomised studies, the addition of anthracyclines increa ses the response rate and statistically significantly improves the survival compared with non-anthracycline containing chemotherapy, except for CMF co mbined with prednisone/prednisolone, which will statistically significantly improve the survival compared with some anthracycline combinations. Second line therapy using vinorelbine or docetaxel is statistically signifi cantly better than other regimens with a time to progression and survival b enefit in the order of one to three months based on few randomised studies. The role, if any, of third line therapy is yet to be demonstrated. In the metastatic setting, conventional chemotherapy improves the quality o f life. In standard care, first line therapy should contain an anthracycline and se cond line therapy using vinorelbine or docetaxel could be offered to select ed patients failing first line therapy. Based on numerous randomised studies. breast cancer demonstrates a positive dose-response relationship both in the adjuvant situation and for metastat ic disease. However. in the conventional dose-range there seems to be a pla teau in the dose-response curve, with no further survival gains for higher doses. High-dose therapy with bone marrow support might result in further increase s in antitumour effects with the potential of increasing survival, but addi tional phase III studies are required before this can be recommended for ro utine care. The growth factors G-CSF and GM-CSF reduce chemotherapy-induced hematologic al toxicity. So far their use has given no proven effect on survival. There is no support that unspecif ic immunomodulation improves the outcome in breast cancer. A clinical benefit from monoclonal HER-2 antibodies is su ggested but needs further confirmation.