Breast metastasis

Among other rare sources of tumors metastasizing to bladder, mammary carcinoma deserves a cautionary note. The possibility of a breast metastasis should be raised when presented with an epithelial infiltration in... 

Antineoplastic agents that cannot be grouped under subheadings 1-9 include miltefosine which is an alkylphosphocholine that is used to treat skin metastasis of breast cancer, and crispantase which breaks down asparagine to aspartic acid and ammonia. It is active against tumor cells that lack the enzyme asparaginase, such as acute lymphoblastic leukemia cells. Side effects include irritation of the skin in the case of miltefosine and anaphylactic reactions in the case of crispantase. Another recent development is the proteasome inhibitor bortezomib which is used to treat multiple myeloma. 

The estrogens are used cautiously in patients with gallbladder disease, hypercalcemia (may lead to severe hypercalcemia in patients with breast cancer and bone metastasis), cardiovascular disease, and liver impairment. 

McKallip RJ, Nagarkatti M, Nagarkatti PS. Delta-9-tetrahydrocannabinol enhances breast cancer growth and metastasis by suppression of the antitumor immune response. J Immunol 2005 174 3281-9. 

DABROSiN c, CHEN J, WANG L and THOMPSON L u (2002) Flaxseed inhibits metastasis and decreases extracellular vascular endothelial growth factor in human breast cancer xenografts. Cancer Lett. 185 (1) 31-7. 

Metastatic breast cancer is not curable, and therapy is intended to palliate symptoms. In most cases, hormonal therapy is the mainstay. While on therapy, patients are monitored monthly for signs of disease progression or metastasis to common sites, such as the bones, brain, or liver. 

Brain metastasis is the most common neurologic complication seen in patients with cancer. Approximately 170,000 patients develop brain metastases in the United States each year.20 Many malignancies are frequently associated with brain metastases (Table 96-7). While melanoma is the tumor type most likely to metastasize to the brain, brain metastases owing to lung and breast cancers are seen more often because they are among the most common cancers. In addition, brain metastasis may be diagnosed at the same time as the primary malignancy in around 20% of cases.22 Around 80% of brain metastases occur in the cerebral hemispheres, 15% in the cerebellum, and 5% in the brain stem. 

Muller A, Homey B, Soto H, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001 410 50-6. 

Kato M, Kitayama J, Kazama S, Nagawa H. Expression pattern of CXC chemokine receptor-4 is correlated with lymph node metastasis in human invasive ductal carcinoma. Breast Cancer Res 2003 5 144-150. 

Helbig G, Christopherson KW, Bhat-Nakshatri P, et al. NF-kB promotes breast cancer cell migration and metastasis by inducing the expression of the chemokine receptor CXCR4. J Biol Chem 2003 278 21631-21638. 

Walser TC, Rifat S, Ma X, et al. Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res 2006 66 7701-7707. 

Urquidi, V., Sloan, D., Kawai, K., Agarwal, D., Woodman, A. C., Tarin, D., Goodison, S. (2002). Contrasting expression of thrombospondin-1 and osteopontin correlates with absence or presence of metastatic phenotype in an isogenic model of spontaneous human breast cancer metastasis. Clin. Cancer Res. 8(1), 61-74. 

Fuqua SA (2001) The role of estrogen receptors in breast cancer metastasis. J Mammary Gland Biol Neoplasia 6 407... 

In humans, also, preferential sites exist for the formation of metastasis from various primary tumors [reviewed in Zetter (Zl)]. Thus, bone is a preferred site for metastasis from primary malignancies in breast, prostate, and kidney, while liver is a frequent metastatic site for tumors originating in the colon. Different types of leukemias vary widely in their ability to spread to liver, lymph, bone, and spleen. Some organs, however, are rarely colonized by metastatic growth. These resistant sites include skeletal muscle, heart, and skin. 

Inverse Relationship between Protease Inhibitors and Metastatic Ability. All proteases, apart from possibly CD, appear to be controlled by endogenous inhibitors. In theory, therefore, the ability of malignant cells to produce metastasis could depend not only on the levels of the specific protease, but also on the concentration of relevant endogenous inhibitors. Thus, the presence of high levels of protease inhibitors might inhibit metastasis, while low levels of inhibitors might enhance metastasis. An inverse relationship between a number of specific inhibitors and metastatic potential has now been shown. Some examples of this type of relationship include TIMP-1 in Swiss 3T3 cells (K4), cysteine protease inhibitors in mouse melanoma cells (R6), and an alpha-1-proteinase inhibitor in rat mammary carcinomas (N2). Furthermore, a newly described serine protease inhibitor, known as maspin, was found to be expressed less frequently in advanced human breast cancers compared with early cancers (Z2). 

Human cancers vary widely in their ability to produce metastasis. At present, there are no reliable methods to predict metastatic potential. For optimum patient management, however, knowledge of the aggressiveness of a tumor is desirable when deciding which patients should receive adjuvant chemotherapy. This type of information is particularly important for axillary node-negative breast cancer and Dukes B colorectal cancer. 

The presence or absence of metastases in local lymph nodes is widely used as a prognostic marker. Generally, patients with metastasis in these lymph nodes have a significantly poorer outcome than those patients without metastases. However, at least in the case of breast cancer, about 25-30% of node-negative patients die from their disease within 10 years. As mentioned earlier, there is a particular urgent need for new markers to identify those high-risk, axillary node-negative breast cancer patients. 

R3. Rochefort, H., Cathepsin D in breast cancer A tissue marker associated with metastasis. Eur. 

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