Abstract
Cyclophosphamide is one of the most frequently used agents in the neoadjuvant, adjuvant, and high-dose chemotherapeutic treatment of breast cancers. Preclinical models indicate that cellular sensitivity to cyclophosphamide and other oxazaphosphorines, e.g., ifosfamide, is inversely related to the cellular content of two aldehyde dehydrogenases, viz ALDH1A1 and ALDH3A1, and glutathione. Breast tumor levels of these "determinants of cellular sensitivity to the oxazaphosphorines" are known to vary widely, and the decision as to whether or not to use an oxazaphosphorine as part of the therapeutic strategy to treat breast cancer in any given patient is likely to depend, in large part, on the levels of these determinants in that cancer. ALDH1A1, ALDH3A1, and glutathione levels can be easily quantified in primary breast tumors and in detectable metastatic breast tumors present in axillary lymph nodes because the amounts of tissue required for the desired analysis can be readily obtained, whereas these levels cannot be quantified in residual metastatic breast cancer cell populations, i.e., those that escape detection and/or that are inaccessible to surgical harvest. The inability to directly quantify residual metastatic breast cancer c...Continue Reading
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