The investigation of high-dose chemotherapy for the treatment of women with breast cancer was supported by laboratory findings that suggested a dose-response relationship for alkylating agents.

Medical advances to support patients through the intensive high-dose therapy permitted the initial investigation of this principle in women with metastatic disease. The use of autologous bone-marrow support with the aid of hematopoietic growth factors and, more recently, peripheral blood-progenitor stem-cell support, has allowed high-dose chemotherapy to be administered with improved safety and reduced morbidity.

Subsequently, small uncontrolled trials of high-dose chemotherapy in high-risk patients with extensive axillary lymph node involvement (10 or more lymph nodes) reported an improved disease-free and overall survival as compared with historical controls.

These patients underwent an extensive screening evaluation prior to receiving high-dose chemotherapy to exclude patients with occult metastatic disease. Such pretreatment testing introduces selection bias, which may explain the favorable results of these uncontrolled trials when compared with historical controls.

Several Phase III randomized trials have been reported recently evaluating the role of high-dose chemotherapy in both the adjuvant and metastatic settings. The trials reported to date have not been shown to improve overall survival in either the high-risk adjuvant or metastatic group. One of the adjuvant trials was initially reported to show a benefit in both relapse-free and overall survival for patients randomized to the high-dose arm. Unfortunately, the results of this trial have been invalidated due to the discovery of scientific misconduct.

Therefore, the role of high-dose chemotherapy with stem-cell support remains an investigational question and should not be offered to women outside of a clinical trial. Future trials are planned to evaluate the efficacy of tandem transplants, as well as the addition of biologic treatments for consolidation.

Maura N. Dickler
American Cancer Society Guidelines for the Early Detection of Breast Cancer: Update 2003. CA Cancer J Clin 2003

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