Considerations in treatment choice for metastatic breast cancer

Chemotherapy treatment choices for metastatic breast cancer (MBC) have become increasingly complex as therapeutic options multiply. In addition, the more frequent use of adjuvant chemotherapy coupled with the introduction of new standard adjuvant therapies has made these choices more difficult. Another issue that remains unsettled is whether to employ combination therapy or to use each agent singly until its value is exhausted. The results of recent studies investigating this issue have revealed higher response rates, time to tumor progression and, in some cases, improved overall survival with doublet therapy. However, there was no planned crossover in these trials and, as such, the absolute benefits of doublet therapy remain undetermined. The future of therapy for MBC appears to be combining effective single-agent chemotherapy with novel biologic agents. For example, compared with paclitaxel alone, therapy comprising paclitaxel plus bevacizumab produced a doubling of response rate and progression-free survival. However, similar data are required for both the first- and the second-line setting, and for other chemotherapy agents, for example, docetaxel and navelbine. Trastuzumab is the treatment of choice for patients with HER2-positive tumors. Its use in combination with chemotherapy, particularly the taxanes, is well established. However, much remains to be learned about biologic agents; for example, trials need to establish whether these therapies should be continued at the time of progression or whether other treatments should be given in their place. A recent study in patients whose disease had progressed after trastuzumab and chemotherapy and who were subsequently given lapatinib, has reported promising outcomes for this agent. When presented with the many options that are now available for the treatment of MBC, we must keep in mind the primary goal of such treatment: palliation of disease with minimal toxicity. Furthermore, a concurrent requirement for prolongation of survival is now commonplace. However, it is clear that there is currently no "gold standard" treatment for MBC, although the future of therapy appears to be the combination of effective single agents with novel biologic therapies.