For patients in whom chemotherapy is recommended, the choice between a single agent or a combination regimen, and the selection of a specific therapy, should take into account several factors in an effort to individualize therapy as much as possible.
Because of the availability of many agents to treat metastatic breast cancer, there is no ideal sequence of treatments that can be applied to all patients. It is likely that patients with metastatic breast cancer will receive many (if not all) of these treatments throughout the course of their disease. However, below we illustrate the principles that can guide the choice of therapy in the first- or later-line setting. Given that currently available systemic treatments for metastatic breast cancer are not curative, we encourage participation in well-designed clinical trials.
Tumor burden (the extent of disease detected on imaging or clinical exam and/or the presence of tumor-related symptoms) can impact on whether single-agent chemotherapy or a combination regimen is administered:
- We prefer the sequential use of single-agent chemotherapy, especially for patients with a limited tumor burden and/or limited or minimal cancer-related symptoms. Sequential single-agent treatment is often less toxic and results in similar overall survival compared with combination chemotherapy .
- For select patients, we favor the use of a combination regimen rather than a single agent because combination therapy results in a higher response rate, which may justify the risks of treatment . Appropriate patients include those with symptomatic disease due to the location of specific metastatic lesions (eg, right upper quadrant pain due to expanding liver metastases, or dyspnea related to diffuse lung metastases), a large tumor burden, and those with rapidly progressive disease.
- For patients with brain metastases, systemic treatment may not be required if there is no evidence of systemic disease. In the presence of systemic disease, treatment of both the central nervous system and systemic disease should be individualized. (See «Management of brain metastases in breast cancer».)
General health status
Treatment decisions should take into account the overall health status of the patient, which can be gauged by the performance status (table 1) or, in the case of older women, a comprehensive geriatric analysis (CGA).
For patients in whom a single agent is recommended, an understanding of the patient’s health status also may influence the appropriate selection of agents. As examples:
- Patients with a history of cardiac disease or heart failure and those who are felt to be at a greater risk for cardiac injury (eg, elderly patients) should not be treated with an anthracycline. There are multiple appropriate alternatives (eg, paclitaxel or capecitabine).
- Patients with symptomatic peritoneal metastases, those who have difficulty swallowing pills, or those who are not able to follow instructions required to use a daily regimen may not be good candidates for oral therapies (eg, capecitabine).
- Patients at risk for hyperglycemia (eg, patients with diabetes) and those who cannot tolerate steroids for whatever reason may derive more of a benefit from agents that do not require premedication (eg, nanoparticle albumin bound [nAb]-paclitaxel, capecitabine, and gemcitabine).
- Patients with a poor performance status or those with significant competing comorbidities may not benefit from treatment at all, especially if they have a higher risk of dying from a cause other than breast cancer. Therefore, the benefits and risks of single-agent therapy should be balanced against overall prognosis.
For patients in whom a combination regimen is preferred, the patient’s health status also can help choose the most appropriate regimen. As examples (see ‘Combination chemotherapy’ below):
- Ideal candidates for an anthracycline-containing regimen include women with chemotherapy naive, stage IV breast cancer (ie, no prior cytotoxic therapy and those who received endocrine therapy initially) and those who did not previously receive an anthracycline (eg, those who received docetaxel plus cyclophosphamide in the adjuvant setting). These are among of the most active regimens for metastatic breast cancer.
- Patients with a cardiac history (including prior anthracycline-induced cardiac injury) should not be treated with an anthracycline. Our preference is to administer a taxane-based regimen (eg, gemcitabine plus paclitaxel or docetaxel).
Prior treatment and toxicities
For the patient who has been previously exposed to chemotherapy (eg, as adjuvant treatment or previous therapy for metastatic breast cancer), there is no optimal sequence of administration of chemotherapy agents used to treat metastatic breast cancer. In general, treatment with chemotherapy drugs of different classes (non-cross resistant agents) may result in a higher probability of response, especially if disease progression occurred within six months following the previously administered regimen . However, the treatment history (ie, agents used and any previous toxicity experienced or persisting) should be reviewed to help inform the choice of a subsequent regimen. As examples:
- Patients who received doxorubicin or epirubicin in the adjuvant setting, even years previously, may not be good candidates for repeat anthracycline therapy due to increasing risk of cardiac toxicity at higher cumulative doses. Of the available alternative agents, we typically administer a taxane in these patients.
- Patients with a history of myelosuppression with prior therapy that resulted in dose modification or treatment delay may not be good candidates for combination chemotherapy, particularly those using agents or schedules with significant myelotoxicity risks (eg, ixabepilone, gemcitabine, and every three-week docetaxel). In these situations, single-agent treatment using a weekly anthracycline, capecitabine, or a weekly taxane may be more appropriate.
- Patients with baseline or a history of serious (grade 3/4) neuropathy may not be good candidates for microtubulin-directed agents (eg, taxanes, ixabepilone, eribulin, or vinorelbine). These patients are appropriate candidates for anthracyclines, especially in the first-line setting in a patient who was never treated with an anthracycline. Alternatives to anthracyclines include capecitabine, etoposide, or gemcitabine.
Patient preferences help to individualize treatment plans for metastatic breast cancer. For example, some patients may not accept the additional risks of toxicity associated with combination chemotherapy if the goal of treatment is not cure (or remission). On the other hand, others may accept a higher chance of a treatment response despite the additional toxicity risks and may opt for combination chemotherapy.
Additional examples include:
- Patients who prefer less frequent visits for intravenous treatments may opt for treatment administered every three weeks, rather than weekly. Appropriate regimens that can be administered every three weeks include single-agent taxanes, anthracyclines, or ixabepilone, or combination therapy using cyclophosphamide, methotrexate, and fluorouracil (CMF) or doxorubicin plus cyclophosphamide (AC).
- Patients who prefer a low risk of alopecia may want to avoid taxanes and anthracyclines (where the risk of alopecia is close to 90%). Options in this circumstance include agents with a lower risk of alopecia, such as gemcitabine (up to 15%) and capecitabine (less than 10%).
- Patients who prefer less intrusion on their lifestyle may opt for an orally administered agent, such as capecitabine, rather than treatments that require intravenous infusion.