Central nervous system metastases in patients with high‐risk breast carcinoma after multimodality treatment

Abstract

Ricin B is a galactose‐binding protein, which contains two binding sites. We have compared the binding properties of the two binding sites of ricin B chain toward different mono‐ and disaccharide ligands. The free energies of binding are calculated using the free energy perturbation simulation (thermodynamic integration method) and linear interaction energy approach using CHARMM force field. The second binding site of the protein was found to be weaker compared to the first. The details of the hydrogen‐bonding scheme suggested the origin of the epimeric specificity of the protein. The reason for the weaker binding capacity of the second binding site has been addressed. © 2006 Wiley Periodicals, Inc. Biopolymers 83: 83–94, 2006 This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

Multifactorial central nervous system recurrence susceptibility in patients with HER2‐positive breast cancer

“…37 More recent series have raised the possibility that with more systemic treatments prolonging survival, such as first-line trastuzumab-based therapy for HER2-positive metastatic breast cancer, 41,42 CNS events may be observed more frequently during breast cancer progression. 5 Three retrospective studies inconclusively evaluated the risk and outcome of CNS metastases in HER2-positive patients with metastatic breast cancer who were receiving trastuzumab compared with those receiving non-trastuzumabbased treatment. 28,29,43 In the current study, CNS metastases-free survival after the first extracranial event was found to be significantly worse for HER2-positive patients receiving first-line trastuzumab than for HER2-negative patients and HER2-positive patients not treated with the drug, with an observed CNS recurrence rate of 21% in patients treated with trastuzumab.…”

“…3,4 On the basis of retrospective observations, risk factors for the development of CNS metastases from breast cancer include patient characteristics such as young age and African-American ethnicity, and biological features of the tumor, including estrogen receptor (ER) negativity, human epidermal growth factor receptor 2 (HER2) positivity, high tumor grade, and BRCA1 phenotype. 1,[5][6][7][8][9][10][11][12][13][14][15][16] HER2 (Her-2/neu, c-erbB-2) is a 185-kilodalton transmembrane tyrosine kinase with extensive homology to the epidermal growth factor receptor. In humans, amplification of the HER2 oncogene occurs in 15% to 20% of primary breast cancer, and is associated with diminished disease-free and overall survival.…”

Correlation Between Quantitative HER-2 Protein Expression and Risk for Brain Metastases in HER-2+ Advanced Breast Cancer Patients Receiving Trastuzumab-Containing Therapy

“…ciated with a higher risk for brain metastases [3][4][5], and there is relatively high concordance for HER-2 status between the primary tumor and brain metastases within the same patient [37,38]. The correlation between high HER-2 expression and a higher risk for brain metastases might be attributable to the specific biology of HER-2-overexpressing tumors [6].…”

“…Brain metastases accompanying breast cancer are associated with a poor prognosis, negatively impact quality of life, and are relatively resistant to systemic therapies. A particularly high risk for brain relapse is associated with overexpression of human epidermal growth factor receptor (HER)-2 or amplification of the HER-2/neu gene [3][4][5], which is most likely related to the molecular characteristics of this tumor type and to the poor efficacy of systemic therapy to prevent brain metastases [6]. Growing evidence suggests that the high incidence of brain metastasis with breast cancer may be attributed to organ-specific tropism [7,8].…”

Antidepressant use and risk of central nervous system metastasis

“…Slimane et al [216] found lung metastasis as the first site of relapse and negative hormone receptor status risk factors for brain metastasis in breast cancer patients, although other studies included young age, tumor size, stage, tumor grade, histology, and human epidermal growth factor receptor 2 (HER2, also known as neu) [187,193,[217][218][219][220][221]. Overexpression of HER2 is repeatedly supported as a risk factor for brain metastasis in breast cancer patients [57,175,193,221,222], and the risk has increased since the development of trastuzumab (Herceptin; Genentech, San Francisco, CA), a monoclonal antibody therapy [57].…”