Endocrine Therapies For Breast Cancer

Breast cancer is the most common female cancer in the Western world (accounting for 28 of all cancers) and the leading cause of death by cancer in women (approximately 20 ). Although the mortality rate has stabilized or decreased, the incidence of breast cancer is still rising in all European countries.1 Around two-thirds of breast cancers are hormone (estrogen)-dependent as they are positive for estrogen receptor alpha (ERa) and or progesterone receptor (PR). As estrogen is the principal...

Cellfree

Circulating cell-free RNA has also been found in the plasma and serum of healthy individu-als,64 with increased levels detected in cancer patients,65-67 including breast cancers.68 Fewer studies have been published than for circulating DNA, in part due to RNA stability problems in stored and freeze-thawed samples,69 and reproducibility problems with RNA analyses.70 Silva et al71 used nested RT-PCR to detect the presence of cytokeratin 19 (CK19) and mammoglobin RNA in plasma as markers of tumor...

Endocrine Resistance And Biology Of The Estrogen Receptor Function

As resistance to endocrine therapy is one of the main challenges in the treatment of ERpositive breast cancer, understanding such processes is of major importance. In particular, deciphering the biology of the ER function, and the proteins which participate in estrogen signaling, it is hoped to improve our knowledge of the events which cause a response to endocrine therapy and thus identify accurate predictive markers for responsiveness to treatment. In early studies, ER was identified as a...

Cellcell adhesion

Epithelial cells mediate intercellular adhesion primarily through adherens junctions, desmo-somes, and gap junctions. The molecules involved in these adhesive complexes - classical cadherins, desmosomal glycoproteins and connexins, respectively - have all been shown to exhibit altered expression in breast cancers. The classical cadherins include E-cadherin, P-cadherin and N-cadherin, and of these the major focus in breast cancer has been E-cad-herin. E-cadherin mediates homophilic...

The Prognostic Impact Of Nodal Micrometastases

Nodal status is generally considered an important prognostic factor. Several studies have highlighted that the volume of metastatic nodal load also represents a prognostic parameter beyond the node-positive versus node-negative status. At one end of the spectrum, metastasis in a large number of lymph nodes is associated with a worse prognosis than the involvement of a few lymph nodes,52,53 or the involvement of a larger proportion of the examined lymph nodes is worse than a lower ratio of...

Morphological Factors Tumor size

The prognostic importance of tumor size is well recognized patients with larger invasive breast carcinomas have a poorer outcome than those with smaller lesions.3-6 Many years ago, Rosen and Groshen4 predicted 20-year relapse-free survival rates for women with tumors < 10mm, 11-13mm, 14-16mm and 17-22 mm in diameter of 88 , 73 , 65 and 59 , respectively. However, the clinical evaluation of tumor size is inaccurate, clinical-pathological agreement is seen in only 54 of cases.7 Radiological...

The stressactivated mitogenactivated protein kinases JNK and p38

As stated above, significant influences on ER and AP-1 signaling may also occur following phosphorylation of the SAPK members Jun kinase (JNK) and p38. While the endpoints of such signaling are likely to be as diverse as for ERK1 2 MAP kinase, as stated above, significant in vitro associations with negative growth regulation in breast cancer cells have been reported for JNK and p38.16,17,53 If represented in clinical breast cancer, therefore, JNK and p38 signaling would perhaps be predicted to...

References

Natural history of untreated breast cancer (1805-1933). Br Med J 1962 2 213-21. 2. Fisher B, Slack NH, Bross IDJ et al. Cancer of the breast size of neoplasm and prognosis. Cancer 1969 24 1071-80. 3. Adair F, Berg J, Joubert L, Robbins GF. Long-term follow-up of breast cancer patients the 30-year report. Cancer 1974 33 1145-50. 4. Nemoto T, Vana J, Bedwani RN et al. Management and survival of female breast cancer results of a national survey by the American...

Contributors

University Medical Center Lapeyronie Hospital Montpellier France Department of Pathology Stavanger University Hospital Stavanger Norway Edinburgh Cancer Research Centre Western General Hospital Edinburgh Scotland Dept of Medical Oncology Imperial College London Hammersmith Hospital London Bacs-Kiskum County Teaching Hospital Division of Radiation Oncology Netherlands Cancer Institute Amsterdam The Netherlands Dept of Histopathology Nottingham University Hospitals Nottingham United Kingdom...

Growth Factorinduced Mitogenactivated Protein Kinase Signaling

The MAP kinase signal transduction pathways are highly conserved signaling cascades which exert a profound effect on cell physiology.5-7 MAP kinase pathways can be activated by a variety of different stimuli, including growth 3S35SS8 BSSSS S S5SSS55 J iS55SS MEKK1-5, MLKs, TAOs, TPL-2, ASK, TAK1 MEKK1-5, MLKs, TAOs, TPL-2, ASK, TAK1 Figure 10.1 The mitogen-activated protein MAP kinase pathways. AP-1, Activator protein 1 ASK, apotosis signal regulating kinases ERK, extracellular signal-regulated...