Recommendation 1: For patients with hormone receptor-positive progressive/metastatic breast cancer, endocrine therapy should be their standard first-line treatment, rather than chemotherapy, except in cases of rapidly life-threatening disease or where there is concern about endocrine therapy resistance. Note: It is important to recall that this recommendation is based on the relative magnitude of the likelihood of having disease respond to chemotherapy versus endocrine therapy, rather than the rate of response, for which there are no good data. The main advantages of this recommendation are: lower toxicity and better quality of life with endocrine therapy compared to chemotherapy (potential benefit: high). The disadvantages are: metastatic lesions may progress rapidly and may be fatal if there is no response to treatment, but this risk is low (potential harms: low). Recommendation 2: Chemotherapy should be given in single-agent sequential regimens rather than combination regimens, but combination regimens should be considered for rapidly life-threatening disease, as the latter may have only one chance of treatment at this point. The main advantages of this recommendation are: are lower toxicity and quality of life (potential benefit: high). The potential disadvantage is that in rapidly progressive, life-threatening disease the opportunity to control the disease may be lost if there is no response to monotherapy (potential harms: high). The main benefit is: lower toxicity and better quality of life with sequential monotherapy regimens compared to combination regimens (potential benefit: high). The harm is that metastatic disease may progress rapidly if it does not respond to monotherapy, but the likelihood of this is low (potential harm: low). Recommendation 3: As for targeted therapy, the role of bevacizumab is controversial, given that it should only be considered with single-agent chemotherapy in the presence of rapidly life-threatening or severe symptoms if it is available, with a view to improving treatment response rates (the rationale is similar to the use of combination chemotherapy in recommendation 2). It is well known that currently in the United States, bevacizumab is approved for this indication because it has not been shown to provide a survival benefit. Other targeted agents should not be added to, or substituted for, chemotherapy unless clinical trials are underway. NOTE: Bevacizumab in combination with single-agent chemotherapy improves treatment response and PFS, but not overall survival. Benefit: is improved disease control (potential benefit: moderate). Potential drawbacks: are its unique side effects, increased treatment costs, and barriers to use (potential harms: high). Recommendation 4: In the field of progressive breast cancer, no single-agent chemotherapeutic agent has been shown to be superior to other single-agent chemotherapies, and there are several effective agents that are all appropriate for first-line use. The strongest evidence of effectiveness includes: paclitaxel and anthracyclines. Other options are capecitabine, gemcitabine, platinum, vincristine, and isabepilone. Treatment selection should be based on the following factors: previous treatment, different toxicities, coexisting disease, and individual patient wishes. Drugs that have been clinically shown to be resistant should no longer be used. Pros: Tailored regimens based on disease control and improvement in quality of life (potential benefit: high). Cons: A less active drug may have been used (potential harms: low). High quality evidence confirms that many single agents are active, but the evidence confirming the superiority of one over the others is not sufficient. Recommendation 5: Chemotherapy should be continued until disease progression as tolerated by the patient, as this will modestly improve OS and improve PFS, but the balance between efficacy and toxicity and quality of life must be measured. For selected patients, short breaks, flexible adjustment of dosing cycles, or switching to endocrine therapy (hormone receptor positive patients) can be given NOTE: It is always known that achieving sustained therapy to achieve a balanced relationship between disease control and increased side effects/toxicity is a difficult task. This balance is influenced by many factors, including the use of the drug (e.g., capecitabine is relatively simple to use long-term, whereas docetaxel can severely limit its duration because of its cumulative toxicity), and achieving this balance requires constant communication between physician and patient. Pros: longer PFS with moderate improvement in OS (potential benefit: high) Cons: longer toxicities (potential harm: moderate) Recommendation 6: Specialized chemotherapy regimens should not be designed for different breast cancer subtypes (e.g., triple-negative breast cancer, lobular carcinoma) because there is a lack of evidence for variability in efficacy with this design. In addition, in vitro drug sensitivity testing should not be used to select treatment regimens. Note: If ongoing or future studies show benefit from such a “tailor-made” regimen, then this recommendation needs to be adjusted. Advantages: No potentially effective treatment is missed, and medical costs of in vitro drug sensitivity testing are saved (potential benefit: high). There is no convincing and reliable evidence for these methods. Moderate, based on expert consensus Recommendation 7: Second-line and beyond may provide clinical benefit and decisions must be made based on prior therapy, toxicity, coexisting disease, and the patient’s own choices. As with first-line therapy, there is no clear evidence of superiority of a particular drug or regimen. Effective drugs in the field of first-line relief therapy are available. Note: Eribulin achieved the most convincing data in terms of survival advantage in a recent large randomized controlled trial compared to the best standard of care regimens, but comparative data are lacking on how well it compares to other different regimens. Pros: Gives patients the opportunity for further disease control with symptom improvement (potential benefit: high) Cons: Toxic reactions (potential harm: high) Multiple randomized studies provide evidence with both high and low levels Strong, based on expert consensus Recommendation 8: Palliative care should be offered throughout the course of palliative care. Diminishing patient benefit as the number of chemotherapy lines increases, and providing only best supportive care without further chemotherapy should also be an option for physicians. Note: Evidence suggests that treatment response to chemotherapy prior to second line strongly influences response to chemotherapy at second line and beyond, and that those patients who do not respond to the initial two lines of pre-treatment are unlikely to respond to third line versus third line onwards. Pros: The approach emphasizes quality of life and is patient-centered (potential benefit: high). Cons: The main concern is the patient’s fear of abandonment and dashed hopes, which can be addressed through effective communication and skillful closure of the patient’s life plan (potential harms: moderate). Moderate, several randomized controlled studies of progressive breast cancer Strong, based on evidence, expert consensus, and another separate expert consensus For patients with progressive breast cancer who have not yet been treated, physicians should encourage all eligible patients to participate in clinical trials. For patients who do not have rapidly life-threatening disease, they should be encouraged to participate in clinical trials that include phase 2 clinical trials or targeted phase 1 clinical trials until all standard lines of relief have been used. The advantage: is that more patients are enrolled in clinical studies, on the one hand patients may receive therapeutic benefit and on the other hand the medical community will benefit from more studies to improve treatment and therapeutic decision making. The potential harm is that they will receive inferior treatments.