Effect Of Primary Breast Cancer Extirpation In Stage Iv Patients

Metastatic breast cancer is considered by many to be an incurable disease and therefore the treatment of such patients, whether with systemic therapy (chemotherapy, hormonal therapy), or with surgery is considered palliative (1). However, it has been suggested by others that there may be role for curative surgery in the treatment of selected patients with metastatic breast cancer (2, 3). Khan et al. were one of the first to describe an aggressive local surgical approach to metastatic breast...

Tight Junctions And Metastasis Of Breast Cancer

Metastasis and Angiogenesis Research Group, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK Abstract TJs are the apical most structure between epithelial and endothelial cells. Although well known as functioning as a control for paracellular diffusion of ions and certain molecules, it has recently become apparent that the TJ has a vital role in maintaining cell integrity and that loss of cohesion of the TJ structure can lead to invasion and thus metastasis of breast...

Desmosomes in breast cancer

Desmosomes are multifaceted intracellular junctions that participate in cell adhesion and maintenance of normal tissue structure. Desmosomes connect epithelial cells, myoepithelial cells, and the two cell types to each other. Despite the strong adhesion that desmosomes provide, the role of desmosomes in breast cancer metastasis is enigmatic. The loss of desmoplakin in breast cancers correlates with amplified proliferation and increased tumor size, suggesting that desmosomal proteins might be...

Adhesion Cadherins As Ligands And As Receptors

Integrins are the sensors of the cancer cells for their surrounding ECM, and participate in the molecular translation of the seed and soil hypothesis by Paget. As mentioned before, the integrin-basement membrane interaction can help in maintaining positional stability in normal epithelia, but in carcinoma many clues indicate that integrins promote motility, invasion, and hence, metastasis. Many data from the recent literature point toward the relation between (over)expression of certain types...

References

Skeletal complications of malignancy. Cancer 1997 80(8 Suppl) 1588-1594 2. Kozlow W, Guise TA. Breast cancer metastasis to bone mechanisms of osteolysis and implications for therapy. J Mammary Gland Biol Neoplasia 2005 10(2) 169-180 3. Fidler IJ. The pathogenesis of cancer metastasis the seed and soil hypothesis revisited. Nat Rev Cancer 2003 3(6) 453-458 4. Paget S. The distribution of secondary growths in cancer of the breast. Cancer Metastasis Rev 1989 8(2) 98-101 5. Hauschka PV,...

Lymphatic and Vascular Invasion LVI

A study involving 1,704 women with early stage breast cancer revealed vascular invasion (lymphatic and or blood vessel) on routine hematoxylin and eosin sections in the tumors of 23 of the examined patients and its presence was associated with both decreased survival and increased local recurrence (28). Similarly, the recurrence rate in 644 women with stage I breast cancer was found to be significantly higher (38 compared to 22 ) in those with vascular invasion than those without (29). A recent...

Hgf Cmet And Metastasis

The presence of metastatic disease in cancer patients is the most significant factor affecting their survival (53). Many studies have demonstrated that tumour cell stimulation with HGF results in an enhancement of cellular functions that are central to the process of metastasis. HGF, upon complexing with its specific receptor, c-Met, evokes an array of biological actions within cancer cells, such as enhanced cell migration, matrix degradation, invasion, and induction of angiogenesis. The...

The Association Between Serum Igf1 And Breast Cancer Risk

Many studies support the role of IGF-1 in malignant transformation of breast epithelia. Animal studies have shown that transgenic mice which over-express growth hormone and IGF-1 exhibit an increased rate of developing mammary tumours (46, 47). Likewise, liver-IGF-1-deficient mice showed a 75 reduction of circulating IGF-1 compared to control mice which also correlated with a significant reduction in risk of mammary tumour development (48) while treatment of primates with growth hormone and...

Internal mammary node

Interest in evaluating internal mammary nodes (IMNs) has recently been rejuvenated with the advent and widespread acceptance of lymphatic mapping and SLNB in breast cancer. The lymphoscintiscan demonstrates mapping to IMNs in 0-35 patients (61-63). In contrast to traditional thinking, internal mammary drainage can occur with tumours in any quadrant (61). Most patients with drainage to internal mammary nodes also have axillary drainage and surgeons are reluctant to perform internal mammary lymph...

Immunoglobulin Superfamily Of Cell Adhesion Molecules

Members of the immunoglobulin superfamily of cell adhesion molecules (Ig-CAM) have 1-7 extracellular immunoglobulin-like domains. They are attached to the plasma membrane by a single, hydrophobic transmembrane sequence and have a cytoplasmic tail (7). They can be involved in both homotypic and heterotypic adhesion (84). ALCAM (activated leukocyte cell adhesion molecule, CD166, human melanoma metastasis clone D MEMD , HB2) is a glycoprotein of the immunoglobulin superfamily that is involved in...

Topoisomerase IIalpha topo IIa expression

The topoisomerase II alpha gene (topo IIa) is located adjacent to the HER2 oncogene at chromosome 17q12-q21. Topo IIa is thought to be the primary molecular target of anthracyclines, as the exposure of cells to topo II inhibitors results in stabilization of covalently bound cleavable complexes and subsequent DNA double-strand breaks (106) and sensitivity to topo II inhibitors including anthracyclines was associated with topo IIa expression (75, 107-109). Furthermore, amplification of the topo...

Info

Metastatic cells need to detach from the primary site and attach at the secondary site. Thus it needs an intricate expression control of various adhesion molecules on the cell surface in space and time (14). Specific families of adhesion molecules whose expression correlates with metastasis include selectins, integrins, lectins, and cadherins. Details about these molecules have been discussed by Shevde and King in chapter 6. The degradation of the extracellular matrix is mediated by a number of...

Steroid Sulphatase

STS is a member of a superfamily of 12 different mammalian sulfatases (89, 90). The gene coding for human STS is located on the distal short arm of the X-chromosome and maps to Xp22.3-Xpter. STS gene is pseudoautosomal and escapes X-inactivation. It has been cloned, characterized, and sequenced (91). On the Y-chromosome, there is a pseudogene for STS, which is transcriptionally inactive as the promoter, and several exons have been deleted. The gene consists of 10 exons and spans 146 kb, with...

Using Serum Igf1 As A Surrogate Endpoint Biomarker Of Developing Primary And Secondary Breast Cancer

The strong association between breast cancer risk and serum IGF-1 has prompted clinical drug trials to use serum IGF-1 as a surrogate endpoint biomarker for predicting risk of developing primary breast carcinogenesis. In this way, circulating IGF-1 could be a cofactor in the development of breast cancer or it may be a by product of other processes that lead to carcinogenesis. As mentioned previously, several case-control studies have shown that serum IGF-1 in premenopausal women could...

Icam1

ICAM-1 (intercellular adhesion molecule-1) is involved in heterotypic adhesion. Rosette et al. (94) studied five breast cancer cell lines and found that ICAM-1 expression on the cell surface positively correlated with metastatic potential. Breast tumors had increased ICAM-1 mRNA levels compared to normal tissue (94). Lynch et al. (95) found that ICAM-1 serum levels were increased in patients with breast carcinoma. ICAM-1 is increased in the tumor cytosol and sera of patients with breast cancer,...

Bone metastases

The bone is the most common site of breast cancer metastasis, with a typical clinical presentation of the new development and onset of bone pain. Through poorly understood mechanisms, breast cancer cells are able to induce osteoclastic activity that results in the destruction of the bony cortex and marrow with subsequent increased propensity for pathological fractures as the bony matrix is weakened (19, 20). Although pathological fractures can develop anywhere within the bony structures, breast...

Lselectin

While there are no studies that report a role for L-selectin in the metastasis of breast cancer, in colon cancer, L-selectin serves as a molecular link between recruitment of inflammatory leukocytes to the sites of tumor cell emboli in microvasculature and their potential to facilitate metastasis (131). Cancer metastasis is also known to be impaired in L-selectin-deficient mice (132). In melanoma, L-selectin and ICAM-1 contribute cooperatively to the antitumor reaction by regulating lymphocyte...

The Role of Matriptase in Cancer

The type II transmembrane serine protease known as matriptase has the potential to mediate the dissolution of extracellular matrix components surrounding tumour cells, catalyse the degradation of intercellular cohesive structures that allows shedding of tumour cells into the extracellular environment, and activate growth and angiogenic factors during tumour progression, and has also recently demonstrated the ability to promote carcinogenesis (142). Breast cancer cells constitutively activate...

The Genetic Control Of Breast Cancer Metastasis

Samant, Oystein Fodstad, and Lalita A. Shevde Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36688, USA Abstract Metastasis of breast cancer is a complex event involving coordinated cross-talk of several proteins. Genes that control the resultant metastasis can be broadly classified as metastasis promoter genes (MPGs) and metastasis suppressor genes (MSGs). There is an explosion of information in the studies that focus on these genes however, thus far, a very few...

The Molecular Basis Of The Tissue Specificity Of Brca1associated Tumors

3.1 Possible tissue-specific genetic instability The exact molecular basis for the tissue-specificity of BRCA1 -related tumors remains elusive. Furthermore, it is unclear why somatic mutations of BRCA1 are rare in sporadic cancer cases. The highly tissue-specific character of BRCA1 -associated tumors stands in stark contrast with the ubiquitous nature of BRCA1 expression, as well as the generality and multiplicity of its reported functions. As reviewed above, compelling evidence strongly...

The Seed And Soil Hypothesis An Explanation For The Preferential Spread Of Cancer Cells

The Seed and Soil Hypothesis was proposed by Stephen Paget in 1889 to explain the preferential spread of breast cancer to bone (3, 4). It states when a plant goes to seed, its seeds are carried in all directions but they can only grow if they fall on congenial soil (4). The seed is the breast cancer cell, which can only grow or form metastases in particular, compatible parts of the body or soils (3). Aspects of both the seed and the soil contribute to the successful formation of a metastasis...

Chemotherapeutic agents commonly used in MBC

Anthracycline antibiotics (doxorubicin and epirubicin) are among the most active drugs in MBC and cause anti-tumour effects by a variety of mechanisms including generation of oxygen free radicals and impairing DNA replication. Recent studies have conferred that overexpression of topoisomerase II alpha (TOP2A) gene may provide as a rational predictive marker for response to anthracycline therapy. It is often co-amplified in 35 of tumours with HER-2 amplification. But its level of overexpression...

The Role of HGFA in Cancer

We have previously reported that HGFA is expressed in a number of human cancer cell lines, including breast, colon, prostate, lung, and liver (106). In addition, we have also demonstrated that the expression of HGFA is upregulated in human breast cancer tissues compared with normal background breast tissues, whereas the levels of the HGFA inhibitors are reduced in breast cancer tissues (26) (Figure 5). This observation is also reported in colorectal carcinomas, where an upregulation of HGFA is...

Bone Forming Breast Cancer Secreted Factors

About 15 of breast cancer bone metastases are osteoblastic (6). Endothelin-1 (ET-1) is a tumor-secreted peptide with a role in osteoblastic bone metastases (16). ET-1 stimulates osteoblast activity and new bone formation (41). It is secreted by breast cancers and cell lines that produce osteoblastic and mixed bone lesions in mouse models e.g., T47D, MCF-7, ZR75.1, and BT483 (16). Invasive breast tumors express higher ET-1 and ETA receptor than nonneoplastic tissue (42). Patients with breast...

List Of Contributors

Al-Rawi, Mahir A., MB, BCh, PhD, Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK Bracke, Marc, PhD, Professor, Laboratory of Experimental Cancer Research, Department of Experimental Cancer Research, Radiotherapy and Nuclear Medicine, University Hospital, De Pintelaan 185, B-9000 Gent, Belgium Chirgwin, John M., PhD, Professor of Internal Medicine, Division of Endocrinology, University of Virginia PO Box 801401, Charlottesville...

Tj And Breast Cancer Metastasis

4.1 Role of TJs in Breast Cancer Metastasis Cancer metastasis proceeds by a series of steps, among which the capacity of cancer cells to invade surrounding normal tissues is of central importance in the dissemination of disease 113 . The interaction between cancer cells and mesothelial cells lining the cavity is crucial for achieving the complex sequence of cancer cell dissemination into the body cavity. In the process of submesothelial invasion of cancer cells, TJs of mesothelial cells may...

EGFR signalling in ERpositive acquired endocrineresistant breast cancer cells

There is now substantial in vitro and in vivo experimental evidence revealing that the control of endocrine-resistant breast cancer growth is a multifaceted event, involving signalling through many different growth factor receptor tyrosine kinases which provide a complex network of interacting signal transduction pathways impinging on tumour proliferation and cell survival parameters 6, 7, and references therein . For example, several studies have established that the intracellular signalling...

Zo3

PAR-3 ASIP, PAR-6 AF-6 s-afadin CASK CAROM 2.1.1 Zonular occludens and PDZ proteins ZO-1 was the first molecule to be identified in TJs, as a phosphorprotein of 210-225 kDa in size 25-26 localised in the immediate vicinity of the plasma membrane of both endothelial and epithelial cells 22 . ZO-1 is concentrated at the TJs although it is also found within the adherens junction, the nucleus and in cells that do not have distinct TJ structure 23 . It is phosphorylated on serine residues under...