Resistance to anthracyclines and taxanes in breast cancer

Abstract

Taxanes and anthracyclines are widely used in chemotherapy regimens for the treatment of invasive breast cancer. Whether used in the neoadjuvant or adjuvant settings, numerous clinical trials have validated their effectiveness in improving both progression-free and overall survival in breast cancer patients. However, while clinical response (decrease in tumor size by palpation) is common, for many patients this response is short-lived, after which tumors become refractory to treatment. In addition, some tumors exhibit innate (intrinsic) resistance to these regimens at the start of treatment. Consequently, the vast majority of patients do not exhibit either a pathologic complete response post-treatment or a survival benefit from chemotherapy. Numerous in vitro studies have identified potential mechanisms of action for the anthracyclines and taxanes and how tumors may evade the cytotoxic properties of these agents, but their clinical relevance remains questionable. In vivo studies of drug resistance are less subject to such criticisms, but false discovery rates can be high, in particular for genomic studies of biomarkers of drug response or resistance. Nevertheless, studies of drug response and resistance are now starting to provide useful tools to distinguish between responding and non-responding tumors and insight on how to best treat patients with tumors that are refractory to treatment.