Search

Greater understanding of the underlying etiology and biology of breast cancer is enabling the clinical development of targeted therapies for metastatic breast cancer (MBC). Following the successful introduction of trastuzumab, the first human epidermal growth factor receptor (HER) biologically targeted therapy to become widely used in MBC patients, other agents have been developed. Novel agents include monoclonal antibodies such as pertuzumab, which bind to receptors on the cell surface, and tyrosine kinase inhibitors (TKIs) such as lapatinib, which target intracellular pathways such as that of the epidermal growth factor receptor. There is also growing clinical experience with antiangiogenic agents, particularly in combination with chemotherapy. These include the monoclonal antibody bevacizumab, which targets vascular endothelial growth factor receptor, and multitargeted TKIs with antiangiogenic and antiproliferative activities, such as sunitinib. Combination treatment with multiple agents targeting both the HER family and angiogenic pathways (e.g., trastuzumab plus bevacizumab) is also showing activity in the clinical setting. Despite recent advances, there are unanswered questions regarding the management of MBC with targeted agents. Future studies are necessary to determine the optimal combinations, doses, and schedules required to maximize clinical activity while minimizing toxicity. Despite the temptation to use a targeted agent in all patients, identification of patient subgroups most likely to benefit must be a key goal and will be critical to the successful future use of these treatments. The aim of this review is to summarize some of the key signaling pathways involved in tumor progression and some of the novel therapies that are in development for MBC. [ABSTRACT FROM AUTHOR]

We presented the case of a 26-year-old woman with a blastic, miliary form of osteosarcomatosis involving the axial skeleton, skull, and long bones to the elbow and knee joint regions who subsequently developed hypocalcemic tetany. Radiologically the lesions mimicked the spread of breast carcinoma, and because of the distribution of the lesions we surmised that the spread was by means of Batson's vertebral plexus of veins. The literature on multiple osteosarcomas was reviewed and an updated clinical subclassification of patients with multiple skeletal osteosarcomas presented. [ABSTRACT FROM AUTHOR]

The article discusses research on the efficacy of the combination of bevacizumab with paclitaxel as a primary chemotherapy for HER-2 negative metastatic breast cancer (MBC). It references a study by K. J. Dedes et al in the 2009 issue of the "European Journal of Cancer." The study used a Markov cohort simulation to follow the clinical course of typical patients with MBC. It also estimated the response rates, adverse effects and transition probabilities based on the result of the E2100 clinical trial. Direct costs of the drug combination were assessed.

Purpose: We conducted a phase I dose-escalation study to define the maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics of alvespimycin (17-DMAG), a heat shock protein 90 (Hsp90) inhibitor, given in combination with trastuzumab., Experimental Design: Patients were treated with trastuzumab followed by intravenous alvespimycin on a weekly schedule. Hsp90 client proteins were measured at baseline and serially in peripheral blood lymphocytes (PBL) during cycle 1. Patients with advanced solid tumors progressing on standard therapy were eligible., Results: Twenty-eight patients (25, breast; 3, ovarian) were enrolled onto three dose cohorts: 60 (n = 9), 80 (n = 13), and 100 mg/m(2) (n = 6). Dose-limiting toxicities (DLT) were: grade III left ventricular systolic dysfunction presenting as congestive heart failure in 1 patient (100 mg/m(2)), and reversible grade III keratitis in two patients (80 mg/m(2)). Drug-related grade III toxicity included one episode each of fatigue, diarrhea, myalgia, and back pain. Common mild to moderate toxicities included diarrhea, fatigue, myalgia, arthralgia, nausea, blurry vision, headache, back pain, and dry eyes. There was one partial response and seven cases of stable disease (range, 4-10 months), all in HER2+ MBC. In addition, an ovarian cancer patient had complete resolution of ascites and pleural effusion that lasted 24.8 months. There was no change in PK upon weekly dosing. Hsp70 effect continued to increase across four weeks and was most pronounced at 80 and 100 mg/m(2)., Conclusion: The combination of alvespimycin and trastuzumab is safe and tolerable at MTD. Antitumor activity was seen in patients with refractory HER2+ MBC and ovarian cancer. The recommended dose of alvespimycin for further study in this combination is 80 mg/m(2) weekly., (©2012 AACR.)

Greater understanding of the underlying etiology and biology of breast cancer is enabling the clinical development of targeted therapies for metastatic breast cancer (MBC). Following the successful introduction of trastuzumab, the first human epidermal growth factor receptor (HER) biologically targeted therapy to become widely used in MBC patients, other agents have been developed. Novel agents include monoclonal antibodies such as pertuzumab, which bind to receptors on the cell surface, and tyrosine kinase inhibitors (TKIs) such as lapatinib, which target intracellular pathways such as that of the epidermal growth factor receptor. There is also growing clinical experience with antiangiogenic agents, particularly in combination with chemotherapy. These include the monoclonal antibody bevacizumab, which targets vascular endothelial growth factor receptor, and multitargeted TKIs with antiangiogenic and antiproliferative activities, such as sunitinib. Combination treatment with multiple agents targeting both the HER family and angiogenic pathways (e.g., trastuzumab plus bevacizumab) is also showing activity in the clinical setting. Despite recent advances, there are unanswered questions regarding the management of MBC with targeted agents. Future studies are necessary to determine the optimal combinations, doses, and schedules required to maximize clinical activity while minimizing toxicity. Despite the temptation to use a targeted agent in all patients, identification of patient subgroups most likely to benefit must be a key goal and will be critical to the successful future use of these treatments. The aim of this review is to summarize some of the key signaling pathways involved in tumor progression and some of the novel therapies that are in development for MBC.

We report the case of a patient with a rare miliary variant of osteosarcoma associated with symptomatic hypocalcemia and review the literature regarding the pathogenesis of multifocal osteosarcoma, treatment options, and the associated hypocalcemia.

Background: Polyunsaturated fatty acids of the omega-6 (omega-6) class, as found in corn and safflower oils, can act as precursors for intermediates involved in the growth of mammary tumors when fed to animals, whereas polyunsaturated fatty acids of the omega-3 (omega-3) class, as found in fish oil, can inhibit these effects. The effects of dietary intervention on the ratios of these fatty acids in breast and other adipose tissues have not previously been prospectively studied., Purpose: The present investigation was conducted to study the impact on the ratio of omega-3 and omega-6 polyunsaturated fatty acid in plasma and in adipose tissue of the breast and buttocks when women with breast cancer consume a low-fat diet and fish oil supplements., Methods: Twenty-five women with high-risk localized breast cancer were enrolled in a dietary intervention program that required them to eat a low-fat diet and take a daily fish oil supplement throughout a 3-month period. Breast and gluteal fat biopsy specimens were obtained from each woman before and after dietary intervention. The fatty acid compositions of specimens of plasma, breast fat, and gluteal fat were determined by gas-liquid chromatography. Statistical analysis involved use of a two-sided paired t test., Results: After dietary intervention, a reduction in the level of total omega-6 polyunsaturated fatty acids in the plasma was observed (P<.0003); moreover, total omega-3 polyunsaturated fatty acids increased approximately three-fold (P<.0001) and the omega-3/omega-6 polyunsaturated fatty acids ratio increased approximately fourfold (i.e., mean values increased from 0.09 to 0.41; P = .0001). An increase in total omega-3 polyunsaturated fatty acids in breast adipose tissue was observed following dietary intervention (P = .04); the omega-3/omega-6 polyunsaturated fatty acid ratio increased from a mean value of 0.05 to 0.07 (P = .0001). An increase in total omega-3 polyunsaturated fatty acids was observed in gluteal adipose tissue following the intervention (P = .05); however, the ratio of omega-3 to omega-6 polyunsaturated fatty acids (mean ratio values of 0.036-0.045; P = .06) was unchanged., Conclusion: Short-term dietary intervention can lead to statistically significant increases in omega-3/omega-6 polyunsaturated fatty acid ratios in plasma and breast adipose tissue. Breast adipose tissue changed more rapidly than gluteal adipose tissue in response to the dietary modification tested in this study. Therefore, gluteal adipose tissue may not be a useful surrogate to study the effect of diet on breast adipose tissue.

Patients with HIV infection frequently develop clinically significant anemia, either as a manifestation of the HIV or as a result of therapy with medications such as zidovudine. Therapy with recombinant human erythropoietin can increase hemoglobin levels in these patients, decreasing transfusion requirements and improving some aspects of the quality of life. Once erythropoietin therapy is started, it is important to monitor patients carefully for the development of iron deficiency and erythrocytosis.

Low dose radiotherapy has been used to treat a variety of benign disorders including Histiocytosis X. Ionizing radiation may be leukemogenic with leukemia developing between 3.5 to 11 years after exposure. Twenty to 30% of these leukemias are chronic myelogenous leukemia (CML). In this report the rare development of PH1 + CML 11 years after radiation therapy for Histiocytosis X is recorded.

GM-CSF has been used successfully in autologous BMTs, and more recently in patients undergoing allogeneic BMT, for acute or chronic leukemia. We report two patients with hepatitis-related aplastic anemia who received recombinant human GM-CSF following HLA-identical sibling allogeneic BMTs. Both patients were conditioned with CY 200 mg/kg given over 4 days and received GM-CSF at 250 micrograms/m2 beginning 6 h after marrow infusion and continuing daily until the absolute neutrophil count was > 1.0 x 10(9)/l for 2 days. Both patients had prompt engraftment, achieving an absolute neutrophil count of > 0.5 x 10(9)/l on day 13. Neither patient had side-effects attributable to the GM-CSF although one patient developed severe acute GVHD after the cessation of GM-CSF therapy. Our experience suggests that GM-CSF can be safely used in aplastic anemia patients undergoing BMT and that GM-CSF may be useful to decrease the incidence of graft failure associated with less intensive conditioning regimens.

Because of age and disease-induced pathophysiologic changes, elderly and diabetic patients are prone to hyperkalemia under even the best of circumstances. Further complicating the situation is the fact that the drugs often prescribed for these populations can affect potassium homeostasis. Drs Rigolin and Chap describe a case in which an elderly diabetic man with azotemia survived extreme drug-induced hyperkalemia.