High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer

Advanced or 'metastatic' breast cancer is cancer that has spread beyond the breast and underarm lymph nodes to other parts of the body. Although metastatic breast cancer is often responsive to conventional chemotherapy it does not provide a cure. The dose of chemotherapy that can be given to an individual is limited because it is unsafe in high doses and can seriously damage the bone marrow, creating high risk of serious infection. One treatment that was considered promising at the start of the 1990's was use of autograft, which involves transplantation of a woman's own bone marrow or peripheral stem cells to regenerate her bone marrow. Autografting allowed the administration of chemotherapy doses many times higher than could otherwise be used. This systematic review aimed to compare the evidence from randomised controlled trials comparing high dose chemotherapy with conventional chemotherapy.

This review identified six randomised trials including 437 women receiving high dose chemotherapy with autograft and 413 women receiving conventional chemotherapy treatment. In the group receiving the high dose chemotherapy, there were 15 treatment-related deaths as opposed to two in the conventional chemotherapy arm. Although the high-dose treatment did not increase overall survival at 5 years compared with conventional treatment, women on the high-dose treatment survived significantly longer before experiencing recurrence of cancer. Treatment side-effects were worse in the high-dose group. On the basis of this review, the authors conclude that high dose chemotherapy with bone marrow or stem cell transplantation should not be given to women with metastatic breast cancer outside of clinical trials.

Authors' conclusions: 

Although there is evidence that high dose chemotherapy and autograft significantly improves event-free survival compared to conventional chemotherapy in women with metastatic breast cancer there is no significant evidence of benefit in overall survival. High dose chemotherapy with bone marrow or stem cell transplantation should not be given to women with metastatic breast cancer outside of clinical trials.

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Background: 

Although metastatic breast cancer is often responsive to conventional chemotherapy, it remains ultimately incurable. Autologous transplantation of bone marrow or peripheral stem cells (in which the patient is both donor and recipient) has been considered a promising technique because it allows much higher doses of chemotherapy to be used.

Objectives: 

To compare the effectiveness of high dose chemotherapy and autologous bone marrow or stem cell transplantation (autograft) with conventional chemotherapy for women with metastatic breast cancer. Outcomes were survival rates, treatment-related toxicity and quality of life.

Search strategy: 

We used the Cochrane Breast Cancer Group search strategy, adding these terms: bone marrow transplantation, stem cell transplantation, autologous stem cell support. The following databases were searched up to August 2010: MEDLINE, EMBASE, The Cochrane Library and ASCO (American Society of Clinical Oncology). We also searched the Cochrane Breast Cancer Group database and trial registries for unpublished trials, and checked the reference lists of articles found.

Selection criteria: 

Randomised controlled trials comparing the effectiveness of high dose chemotherapy and autograft with conventional chemotherapy for women with metastatic breast cancer.

Data collection and analysis: 

Six randomised controlled trials met the inclusion criteria. Two independent reviewers extracted data.

Main results: 

In total 437 eligible women were randomised to receive high dose chemotherapy with autograft and 413 were randomised to receive conventional treatment. There were fifteen treatment-related deaths among the high dose group and two in the control (conventional dose) group (RR 4.08, 95% CI 1.40 to 11.93). There was no statistically significant difference in overall survival between the high dose and control groups at three years or five years. At five years of follow up, there was a statistically significant difference in event-free survival, favouring the high dose group (RR 2.84, 95% CI 1.07 to 7.50). Toxicity was more severe in the high dose group. Only one of the trials has followed up all women for five years.

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