breast surgery associated with systemic treatment for women diagnosed with metastatic breast cancer. chemotherapy chemotherapy is one of the most important components of therapy for metastatic breast cancer. therapy of choice is based on three variables; 1. the extent, pattern and aggressiveness at first presentation. 2. what stage of menopause the patient is at. 3. what receptor hormone the tumour has. observation of metastases provides direct feedback on the effectiveness of the treatment and often a number of chemotherapy agents are tried sequentially to determine one that works. adding one or more chemotherapy drugs to an established regimen in women with metastatic breast cancer gives greater tumour shrinkage on imaging but also increased toxicity. combination chemotherapy is often used in patients with metastatic breast cancer. research suggests no difference in overall survival time between sequential single agent chemotherapy and combination chemotherapy. sequential single agent chemotherapy may have a more positive effect on progression-free survival. taxanes are very active in metastatic breast cancer, and abraxane is approved for patients with metastatic breast cancer who either relapsed within six months of adjuvant chemotherapy or failed to respond to combination chemotherapy. this has a higher response rate than solvent-based paclitaxel (15% vs 8%). abraxane can also deliver a 49% higher dose of medication than solvent-based paclitaxel; however, the side effects are severe and include chemotherapy-induced peripheral neuropathy. in women with metastatic breast cancer, taxane-containing chemotherapy regimens appear to improve survival and tumour shrinkage and decrease time to progression. taxanes are associated with increased risk of neuro-toxicity and less nausea and vomiting when contrasted to non-taxane containing regimens. vinorelbine is also active in metastatic breast cancer. eribulin was approved in the us in nov 2010. a targeted therapy drug, kadcyla, was approved in february 2013. this antibody-drug conjugate targets only cancerous cells. it works by only releasing its toxic payload when triggered by a protein found in the cancerous cells in her2+ breast cancer. it has extremely low side effects using this target therapy method. platinum-containing chemotherapy regimens are known to be effective for treating a variety of different cancer types. in women with metastatic breast cancer who do not have triple negative disease, there is little or no survival benefit and excess toxicity from platinum-based regimens. however, in women with metastatic triple negative breast cancer, there may be a moderate survival benefit from platinum-based regimens. antitumour antibiotics are also used in metastatic breast cancer. antitumour antibiotics work to prevent cancer cells multiplying by damaging them or stop cell growth. a meta-analysis has demonstrated that women taking antitumour antibiotics as part of their regimen had an advantage in time to progression and tumour shrinkage, but also increased side effect such as cardiotoxicity, leukopenia and nausea. tamoxifen and other anti-estrogens for estrogen-receptor-positive metastatic breast carcinoma the first line of therapy is often tamoxifen or another anti-estrogen drug unless there are liver metastases, significant lung involvement, rapidly progressive disease or severe symptoms requiring immediate palliation. radiotherapy radiotherapy is used in the treatment of metastatic breast cancer. the most common reasons for a patient with metastatic breast carcinoma to be treated with radiotherapy are: spinal cord compression. spinal-cord compression is an oncological emergency, as untreated spinal cord compression may cause permanent paralysis or death. in breast cancer, spinal-cord compression occurs when a bone metastasis or spinal metastasis begins to push on the spinal cord this results in inflammation and, if untreated, spinal cord injury. radiotherapy is an important component of therapy for cord compression secondary to metastatic breast cancer, along with corticosteroids and laminectomy. liver metastases. typically, pain from liver metastases responds to chemotherapy and analgesia. however, in cases when chemotherapy is contraindicated or the liver metastases are refractory to chemotherapy (and pain medication fails to provide appropriate palliation of liver metastasis-related pain, radiotherapy should be considered; it may relieve pain and shrink the metastases, and perhaps extend survival in a subset of patients with a good response to radiotherapy. brain metastases. brain metastases occur in up to 10–15% of breast-cancer patients, and often (but not always) occur late in the disease. they require urgent treatment; brain metastases may progress rapidly, and can suddenly produce life-threatening complications such as increased intracranial pressure, herniation of the brain, and seizures. radiotherapy is essential in the treatment of brain metastases from breast cancer, as it halts tumor progression quickly and can induce a response in the majority of patients. bone metastases. the bones are a very common site of metastatic disease from breast cancer, and bone metastases can cause severe pain, hypercalcemia and pathologic fracture. radiotherapy is indicated to prevent pathologic fracture; it is also part of postoperative treatment following repair of a pathologic fracture. strontium 89, a radiopharmaceutical which is injected into the bloodstream, is under investigation for the treatment of bone metastases from breast cancer; there is evidence that it can relieve pain for up to three months after its administration. it is unknown whether or not it can prevent pathologic fracture, but it should be considered in patients who have three or more sites of painful bone metastases who cannot be treated with external-beam radiotherapy. in some patients with estrogen-receptor-positive breast carcinoma metastatic to the bone only, external-beam radiotherapy followed by tamoxifen or another anti-estrogen may be sufficient to control disease, at least temporarily. in most cases, however, the combination of radiotherapy and hormonal therapy is not enough to maintain disease control, and chemotherapy is needed. "alternative" and "complementary" therapies some patients with metastatic breast cancer opt to try alternative therapies that are claimed to achieve healing effects similar to scientifically-tested medical approaches, but lack scientific evidence to support those claims. approaches that are considered alternative therapies when applied to cancer treatment include vitamin therapies, homeopathic treatments, extreme diets, chiropractic treatment and acupuncture. some alternative treatments are harmful or even life-threatening. amygdalin, an extract derived from apricot kernels, exposes the patient to cyanide. bee venom can cause a life-threatening allergic reaction. severe dietary restrictions such as macrobiotic diets can disrupt the body’s metabolism and cause dangerous weight loss. people should be aware that foods, vitamins, and other treatments may interfere with the effectiveness of surgery, chemotherapy or radiation. it is essential that patients work with their doctors and openly discuss possible effects of any treatment they are considering. alternative and complementary therapies are not regulated by the u.s. federal government and may lack quality controls. while there is no evidence that any alternative treatments will cure cancer, there are treatments that may alleviate symptoms and improve quality of life for patients. when integrated into a broader medical treatment plan these are sometimes referred to as "complementary" or "integrative" therapies. for example, patients may find hypnosis, massage, meditation, relaxation techniques, tai chi or yoga to be helpful for issues such as stress, pain, nausea, and difficulty sleeping. gentle exercise and a healthy diet can contribute to overall well-being and quality of life. some early research suggests that women who refrain from eating for at least 13 hours overnight are less likely to have a cancer recurrence, possibly due to differences in insulin, ketone or glucose metabolism. as yet, the effects of nutrition and exercise on cancers are not well understood and some theories are controversial. patients have been shown to face a greater risk of mortality if they refuse or delay scientifically-proven treatments in favor of alternative therapies. this is also true in the case of complementary therapies. a study published in jama oncology compared the survival of those who used complementary cancer treatments and those who used only the medical cancer treatments recommended by their doctors. they found that those who used complementary treatments during cancer treatment were more likely to refuse some of the conventional cancer treatments their doctors recommended, resulting in a higher risk of dying as compared to those who used no complementary treatments at all. those most likely to choose complementary treatments were young, affluent, well-educated women with private insurance. "complementary medicine can be quite useful when used in addition to all physician-prescribed cancer therapies,” says dr. park. “however, what is harmful is when patients believe that they can use it to replace surgery, radiation therapy, chemotherapy, hormonal therapy, or immunotherapy, or if it is used without the knowledge of their cancer physicians." experimental therapies treatment of metastatic breast cancer is currently an active area of research. several medications are in development or in phase i/ii trials. typically new medications and treatments are first tested in metastatic cancer before trials in primary cancer are attempted. another area of research is finding combination treatments which provide higher efficacy with reduced toxicity and side effects. experimental medications: sorafenib a combined tyrosine protein kinases inhibitor. scheduling of drug treatments and impact on results scheduling of drug treatments and combination treatment can have substantial impact on treatment efficacy. nanotherapies using nanoprobes nanomedicine is being studied, and there are several developments involving the targeting of cancer cells using nanoprobes. some instances where nanoprobes are used to target specific tumor cells (based on the organ to which they have metastasized) are: chlorotoxin (a chemical derived from the deathstalker scorpion) binds to mmp-2 to cause endocytosis of the metalloprotease, thus reducing its activity. chemically bonded iron-oxide nanoparticles were coated with about 20 molecules of chlorotoxin and targeted to brain-metastatic cancer cells. it was found that nanoprobes reduced brain-metastatic tumors in mice by 98%. nanotherapy using antibodies to herceptin (coated on gold nanoparticles) has slowed down the growth and invasion of aggressive breast tumors in mice. such therapies, targeted to specific cell types, is hoped to be useful in the future to develop better treatments to prevent or treat metastasis in breast cancer. central nervous system metastases