Molecular analysis of metaplastic breast carcinoma: high EGFR copy number via aneusomy.

Metaplastic breast carcinoma, a rare tumor composed of adenocarcinomatous and nonglandular growth patterns, is characterized by a propensity for distant metastases and resistance to standard anticancer therapies. We sought confirmation that this tumor is a basal-like breast cancer, expressing epidermal growth factor receptor (EGFR) and stem cell factor receptor (KIT). EGFR activating mutations and high copy number (associated with response to tyrosine kinase inhibitor gefitinib) and KIT activating mutations (associated with imatinib sensitivity) were then investigated. Seventy-seven metaplastic cases were identified (1976-2006); 38 with tumor blocks available underwent pathologic confirmation before EGFR and KIT immunohistochemical analyses. A tissue microarray of malignant glandular and metaplastic elements was constructed and analyzed immunohistochemically for cytokeratin 5/6, estrogen receptor, progesterone receptor, and p63, and by fluorescence in situ hybridization for EGFR and HER-2/neu. DNA isolated from individual elements was assessed for EGFR and KIT activating mutations. All assessable cases were negative for estrogen receptor, progesterone receptor, and (except one) HER2. The majority were positive for cytokeratin 5/6 (58%), p63 (59%), and EGFR overexpression (66%); 24% were KIT positive. No EGFR or KIT activating mutations were present; 26% of the primary metaplastic breast carcinomas were fluorescence in situ hybridization-positive, displaying high EGFR copy number secondary to aneusomy (22%) and amplification (4%). We report here that metaplastic breast carcinoma is a basal-like breast cancer lacking EGFR and KIT activating mutations but exhibiting high EGFR copy number (primarily via aneusomy), suggesting that EGFR tyrosine kinase inhibitors should be evaluated in this molecular subset of breast carcinomas.

Ramifications of severe organ dysfunction in newly diagnosed patients with small cell lung cancer: contemporary experience from a single institution.

Small cell lung cancer is highly sensitive to chemotherapy, and a survival advantage with its use is well established. However, whether chemotherapy also confers such benefits to patients with severe organ dysfunction has not been extensively studied. The goal of this study was to provide further guidance for clinical decision-making. Medical records from small cell lung cancer patients who were seen at a single tertiary care institution between 1994 and 2002 were reviewed. All patients with severe organ dysfunction were identified. The latter was defined as creatinine >/=3mg/dl, total bilirubin>/=3mg/dl, and/or platelet count

The cancer anorexia/weight loss syndrome: therapeutic challenges.

The cancer anorexia/weight loss syndrome is characterized by loss of weight, loss of appetite, overall decline in quality of life, and shortened survival in patients with advanced incurable cancer. It is highly prevalent. To date, treatment options that have been firmly established with good scientific evidence are limited to progestational agents and corticosteroids, both of which have been demonstrated to improve appetite but have otherwise failed to have a favorable impact on some of the other aspects of this syndrome. As the mechanisms behind this syndrome are further elucidated, more effective therapeutic strategies will likely emerge.