Breast Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage IIIB, Inoperable IIIC, IV, Recurrent, and Metastatic Breast Cancer
Combination regimens that have shown activity in metastatic breast cancer:
- CA: cyclophosphamide and doxorubicin.
- Docetaxel and doxorubicin.
- CAF: cyclophosphamide, doxorubicin, 5-fluorouracil.
- CMF: cyclophosphamide, methotrexate, 5-fluorouracil.
- Doxorubicin and paclitaxel.[84,85]
- Docetaxel and capecitabine.
- Vinorelbine and epirubicin.
- Capecitabine and ixabepilone.
Whether single-agent chemotherapy or combination chemotherapy is preferable for first-line treatment is unclear. An Eastern Cooperative Oncology Intergroup study (E-1193) randomly assigned patients to receive paclitaxel and doxorubicin given both as a combination and sequentially. Although response rate and time-to-progression were both better for the combination, survival was the same in both groups.[Level of evidence: 1iiA];[90,91] The rate of disease progression, the presence or absence of comorbid medical conditions, and physician/patient preference will influence the choice of therapy in individual patients. At this time, no data support the superiority of any particular regimen. Sequential use of single agents or combinations can be used for patients who relapse. Combinations of chemotherapy and hormone therapy have not shown an OS advantage over the sequential use of these agents.[15,92] 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.[Level of evidence: 1iiA]
The optimal treatment duration 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 from immediate treatment with a different chemotherapy regimen compared to observation with treatment upon relapse.[94,95][Level of evidence: 1iiA] Neither of these studies, however, showed an improvement in OS for patients who received immediate treatment, and in one of these studies, survival was actually worse in the immediately treated group. Similarly, no difference in survival was noted when patients with partial response or stable disease after initial therapy were randomized to receive either a different chemotherapy versus observation  or a different chemotherapy regimen given at higher versus lower doses.[Level of evidence: 1iiA] These four studies indicate that different combination regimens of additional chemotherapy immediately following a patient's best response to an induction chemotherapy regimen does not improve OS. In view of the lack of a standard approach, patients requiring second-line regimens are good candidates for clinical trials.