Evolving Approaches to Metastatic Breast Cancer Previously Treated with Anthracyclines and Taxanes

Despite major advances in the adjuvant treatment of breast cancer, many women will develop metastatic disease, either de novo or following optimal adjuvant therapy. Further effective therapeutic options are needed for women who progress following anthracycline- and taxane-containing regimens. Capecitabine is approved by the US Food and Drug Administration as monotherapy in this setting. Other agents such as gemcitabine or vinorelbine might be considered based on multiple phase II studies. Combination therapies generally increase response rates but with a concomitant increase in toxicity. Other agents that have been studied in this setting include etoposide, irinotecan, and pemetrexed. Novel agents undergoing testing include the fluorinated vinca alkaloid vinflunine and the halichondrin B analogue eribulin. Responses have been seen in taxone-pretreated patients with the use of another conventional taxane, novel formulations, or alternative schedules. Pegylated liposomal doxorubicin might be considered in some patients for whom there is a concern regarding cardiac toxicity with the conventional preparation. The epothilones are a novel group of microtubule-stabilizing agents. lxabepilone is a member of this class that has been approved as monotherapy in patients whose tumors are resistant or refractory to anthracyclines, taxanes, and capecitabine. It is also approved with capecitabine in patients whose cancer is resistant to treatment with anthracyclines and taxanes. Decision-making regarding treatment selection must take into account multiple patient and tumor factors. The therapeutic indices of the available treatments should be considered in the context of the individual patient.