Mechanisms of drug resistance in breast cancer

Drug resistance is one of the most important problems in the treatment of cancer. Patients become resistant not only to the drugs used initially, but also those to which they have not yet been exposed. A number of factors influence the therapeutic outcome of patients with breast cancer, foremost of which is the tumor burden. The greater the tumor burden, the more difficult it is to achieve an adequate and lasting response. Timing of treatment, dose and schedule of therapy, and the duration of therapy are also important considerations in the therapeutic outcome. Of primary importance is the development of drug resistance, which appears to be related to genetic alterations that result in altered cellular pharmacology and lead to reduced drug efficacy. Multiple mechanisms may be involved, all or any number of which may occur simultaneously within each cell, producing an overall drug-resistant phenotype.