Chemotherapy for Metastatic Breast Cancer

Patients receiving hormone therapy whose tumors have progressed are candidates for cytotoxic chemotherapy. There are no data suggesting that combination therapy results in an OS benefit over single-agent therapy. Patients with hormone receptor–negative tumors and those with visceral metastases or symptomatic disease are also candidates for cytotoxic agents.[92]

Single agents that have shown activity in metastatic breast cancer include:

Combination regimens that have shown activity in metastatic breast cancer include:

There are no data suggesting that combination therapy results in an OS benefit over single-agent therapy. An ECOG intergroup study (E-1193) randomly assigned patients to receive paclitaxel and doxorubicin, given both as a combination and sequentially.[121] Although response rate and time to disease progression were both better for the combination, survival was the same in both groups.[121][Level of evidence A1]; [122,123]

The selection of therapy in individual patients is influenced by the following factors:

Sequential use of single agents or combinations can be used for patients who relapse with metastatic disease. Combination chemotherapy is often given if there is evidence of rapidly progressive disease or visceral crisis. Combinations of chemotherapy and hormone therapy have not shown an OS advantage over the sequential use of these agents.[124,125] A systematic review of 17 randomized trials found that the addition of one or more chemotherapy drugs to a chemotherapy regimen in the attempt to intensify the treatment improved tumor response but had no effect on OS.[126][Level of evidence A1]

The following factors may be considered for decisions regarding the duration of chemotherapy:

The optimal time for patients with responsive or stable disease has been studied by several groups. For patients who attain a complete response to initial therapy, two randomized trials have shown a prolonged DFS after immediate treatment with a different chemotherapy regimen compared with observation and treatment upon relapse.[127,128][Level of evidence A1] Neither of these studies, however, showed an improvement in OS for patients who received immediate treatment; in one of these studies,[128] survival was actually worse in the group that was treated immediately. Similarly, no difference in survival was noted when patients with partial response or stable disease after initial therapy were randomly assigned to receive either a different chemotherapy versus observation [129] or a different chemotherapy regimen given at higher versus lower doses.[130][Level of evidence A1] However, 324 patients who achieved disease control were randomly assigned to maintenance chemotherapy or observation. Patients who received maintenance chemotherapy (paclitaxel and gemcitabine) had improved PFS at 6 months and improved OS. This was associated with an increased rate of adverse events.[131][Level of evidence A1] Because there is no standard approach for treating metastatic disease, patients requiring second-line regimens are good candidates for clinical trials.