Median survival from metastatic breast cancer is 12 months without treatment, but young people can survive up to 20 years with the disease, whereas in other metastatic cancers this would be considered unusual.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of first-line hormonal treatment? What are the effects of second-line hormonal treatment in women who have not responded to tamoxifen? What are the effects of first-line chemotherapy? What are the effects of first-line chemotherapy in combination with a monoclonal antibody? What are the effects of second-line chemotherapy? What are the effects of treatments for bone metastases? What are the effects of treatments for spinal cord metastases? What are the effects of treatments for cerebral or choroidal metastases? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 77 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: first-line hormonal treatment using anti-oestrogens (tamoxifen), ovarian ablation, progestins, selective aromatase inhibitors, or combined gonadorelin analogues plus tamoxifen; second-line hormonal treatment using progestins or selective aromatase inhibitors; first-line non-taxane combination chemotherapy; first-line taxane-based combination chemotherapy; first-line high- versus low-dose standard chemotherapy; first-line chemotherapy plus monoclonal antibody (bevacizumab, trastuzumab); first-line chemotherapy plus tyrosine kinase inhibitor (lapatinib); second-line taxane-based combination chemotherapy; second-line capecitabine or semi-synthetic vinca alkaloids for anthracycline-resistant disease; second-line chemotherapy plus tyrosine kinase inhibitor (lapatinib); and treatment for bone, spinal, or choroidal metastases using bisphosphonates, intrathecal chemotherapy, radiotherapy (alone or plus corticosteroids) radiation sensitisers, or surgical resection.
Median survival from metastatic breast cancer is 12 months without treatment, but young people can survive up to 20 years with the disease, whereas in other metastatic cancers this would be considered very unusual.
Anti-oestrogens (tamoxifen) result in tumour responses in about one third of women with oestrogen receptor-positive metastatic breast cancer when used as first-line treatment, but most women eventually develop resistant disease.
Progestins and ovarian ablation may be as effective as tamoxifen as first-line treatment but are associated with more adverse effects, while adding tamoxifen to gonadorelin analogues increases survival and response rates.Selective aromatase inhibitors may be as effective in delaying disease progression as tamoxifen for first-line treatment, and as effective as tamoxifen or progestins as second-line treatment in postmenopausal women, with similar overall survival. The benefit may be greatest in oestrogen receptor-positive women.
Hormonal treatment using tamoxifen or progestins may be preferable to chemotherapy as first-line treatment in women with oestrogen receptor-positive disease.
First-line chemotherapy is associated with an objective tumour response in 40% to 60% of women, of median duration of 6 to 12 months. Complete remission may occur in some women, whereas others show little or no response.
First-line classical non-taxane combination chemotherapy, especially those containing anthracyclines, may be more effective than modified regimens and as effective as hormonal treatments in prolonging survival.The optimum duration of chemotherapy is unknown. Increasing the dose may increase serious adverse effects without prolonging survival.
Adding trastuzumab to standard first-line chemotherapy increases response rates and overall survival in women with HER2/neu overexpression, but risks of cardiac function are increased in women also receiving anthracyclines.
Adding bevacizumab or lapatinib to standard first-line chemotherapy may also be more effective than standard chemotherapy alone but we cannot be certain as high-quality evidence is still emerging.
Taxane-based chemotherapy may increase tumour response and survival compared with some non-taxane regimens as second-line treatment. No clear benefit has been found in first-line treatment.
We don't know how capecitabine or semisynthetic vinca alkaloids perform as second-line treatment for anthracycline-resistant disease.
Adding bevacizumab or lapatinib to capecitabine may also be more effective at increasing response rates and improving quality of life than second-line capecitabine alone, and adding lapatinib may also increase survival, but we cannot be certain as high-quality evidence is still emerging.
Bisphosphonates reduce skeletal complications from bone metastases, while radiotherapy may reduce pain and complications from bone metastases, cranial nerve or spinal cord compression, and in brain or choroidal metastases.