Metastatic breast cancer
The cells have often developed resistance to several lines of previous treatment and have acquired special properties that permit them to metastasize to distant sites.
[5] Typical environmental barriers in a metastatic event include physical (a basement membrane), chemical (reactive oxygen species or ROS, hypoxia and low pH) and biological (immune surveillance, inhibitory cytokines and regulatory extra-cellular matrix (ECM) peptides) components.
[6] Organ-specific anatomic considerations also influence metastasis; these include blood-flow patterns from the primary tumor and the homing ability of cancer cells to certain tissues.
There is increased expression of protease systems in cancer cells, to equip them with the tools necessary to degrade the extracellular matrix and release growth factors or transmembrane receptors.
Interactions of the breast cancer cells with integrins, fibronectin, laminins, collagens, hyaluronan and proteoglycans can contribute to the metastatic process.
Fibronectin is an extracellular glycoprotein that can bind to integrins and other ECM components like collagen, fibrin and heparan sulphate proteoglycans(HSPGs).
Heparanase expressed by cancer cells participates in angiogenesis and neovascularization by degrading the polysaccharide scaffold of the endothelial BM, thereby releasing angiogenic growth factors from the ECM.
MMP-19 cleaves components of the basal lamina such as collagen type IV, laminin 5, nidogen (entactin) and other ECM proteins such as tenascin, aggrecan and fibronectin.
Therefore, endoglin over-expression alters the proteolytic balance of the cells to greater matrix degradation and increased invasive properties of breast cancer.
MMP-2 is the main metalloprotease secreted by breast-cancer cells or induced in the adjacent bone stroma; it plays an important role in the degradation of the extracellular matrix essential for metastasis.
CD44 (a cell-surface transmembrane glycoprotein) is a receptor for hyaluronic acid, involved in cell adhesion by binding to specific extracellular matrix components.
A proposed mechanism for the function of CD44 is to regulate the adhesion of circulating cancer cells in the brain to the endothelium at the secondary site with the help of a hyaluronate matrix ligand or by its cytoplasmic attachments to actin-associated proteins of the merlin/ezrin/radixin/moesin family.
[17] MRI or the combination PET-CT may be considered for cases of abnormal radionuclide uptake on bone scan, when radiography does not give an acceptably clear result.
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; and 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.
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.
[23] 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.
[24] 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.
[25] 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.
[30] 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.
[31] 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.
CNS metastases are often viewed by patients and doctors as a late complication of metastatic breast cancer for which few effective treatments exist.
According to Weil et al., 2005, neuroimaging such as Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) prove to be very effective in the diagnosis of brain and central nervous system metastases.
Effective treatments for brain metastases from breast cancer exist, although symptomatic therapy alone may be chosen for those with poor performance status.
Corticosteroids are crucial to the treatment of brain metastases from any source (including the breast), and are effective in reducing peri-tumoral edema and providing symptomatic relief.
Chemotherapy has not been found to be effective in the treatment of brain metastases from breast cancer, due to the inability of most chemotherapeutic agents to penetrate the blood–brain barrier.
Adjuvant radiotherapy follows surgical resection; this combined approach has been shown to prolong median survival up to 12 months, depending on the factors noted above.
Mean survival from diagnosis of a brain metastasis varies between studies, ranging from 2 to 16 months (depending on involvement of the CNS, the extent of the extra-cranial metastatic disease, and the treatment applied).
