© 2005 Oxford University Press
IN THIS ISSUE |
In This Issue
Locoregional Radiation Therapy in High-Risk Breast CancerIn the British Columbia randomized radiation therapy trial, premenopausal patients with lymph node-positive breast cancer treated by mastectomy and adjuvant chemotherapy were randomly assigned to no additional treatment or to receive locoregional radiation therapy. After 20 years of follow-up for this trial, Ragaz et al. (p. 116) report that radiation therapy and chemotherapy, compared with chemotherapy alone, was associated with a statistically significant improvement in all end points analyzed, including isolated locoregional recurrence, systemic relapse-free survival, disease-free survival, event-free survival, breast cancer death-free survival, and overall survival. In addition, long-term toxic effects, including cardiac deaths were acceptable for both arms. The authors conclude that, for patients with high-risk breast cancer treated with modified radical mastectomy, combined treatment with radiation therapy and adjuvant chemotherapy leads to better survival outcomes than chemotherapy alone, and it is well tolerated with minimal long-term toxicity.
In an editorial, Whelan and Levine (p. 82) say that most clinicians use locoregional radiation after mastectomy for high-risk patients but few accept its use for patients at lower risk. They note that results from two ongoing trials should clarify the use of regional radiation therapy for patients treated with breast-conserving surgery. They add that randomized controlled trials should be mounted to resolve uncertainties about the effectiveness of locoregional radiation therapy after mastectomy in moderate-risk patients.
DNA Repair and Breast Cancer Risk
To determine if interindividual differences in DNA repair capacity are associated with breast cancer risk, Kennedy et al. (p. 127) tested the DNA repair capacity of sisters discordant for breast cancer (158 breast cancer patients and 154 control sisters) from 137 families registered in the Metropolitan New York Registry of Breast Cancer Families. The authors treated lymphoblastoid cell lines developed from each of the participants with the carcinogen benzo[a]pyrene diolepoxide and measured subsequent DNA repair. After adjustments were made for age at blood donation, body mass index, and smoking, the results showed that breast cancer patients had lower DNA repair capacity than the control sisters and that the strength of the association with breast cancer increased as DNA repair capacity decreased. The authors conclude that deficient DNA repair capacity is associated with increased breast cancer risk.
In an editorial (p. 84), Berwick discusses the difficulties researchers face when designing experiments related to DNA repair and cancer as well as the results of Kennedy et al. and their potential limitations. She states that the assay developed by Kennedy et al. is important and that high-throughput assays should be developed so that designing prospective studies with the goal of developing interventions to reduce cancer incidence and mortality will be feasible.
Role of Human Cripto-1 in Tumor Angiogenesis
Human cripto-1 (CR-1) promotes cell transformation and increases migration and invasion of various mouse and human epithelial cell lines. Bianco et al. (p. 132) investigated whether CR-1 also stimulates angiogenesis by using human umbilical vein endothelial cells (HUVECs) and CR-1-transfected MCF-7 human breast cancer cells and a blocking anti-CR-1 monoclonal antibody. They found that addition of CR-1 to HUVECs in vitro stimulated HUVEC proliferation, migration, and invasion and induced their differentiation into vascular-like structures on a Matrigel substrate. In vivo CR-1 protein induced microvessel formation in Matrigel-filled cylinders that was inhibited by the blocking anti-CR-1 antibody. Tumors formed by CR-1-transfected MCF-7 cells in nude mice had a higher microvessel density than tumors formed by control MCF-7 cells. The authors concluded that CR-1 appears to have an important role in angiogenesis.
Increase in Esophageal Cancer Incidence
Although still a relatively rare cancer, esophageal adenocarcinoma incidence has risen dramatically in the past 25 years. To determine if the rise in incidence was real or the result of classification changes or overdiagnosis, Pohl and Welch (p. 142) analyzed incidence, stage distribution, and disease-specific mortality for esophageal and related cancers from the Surveillance, Epidemiology, and End Results database. From 1975 to 2001, the incidence of esophageal adenocarcinoma rose approximately sixfold, and, from their analysis, the authors ruled out reclassification of squamous cell carcinoma and reclassification of adjacent gastric cancer as explanations for the rise. Because esophageal adenocarcinoma mortality has also risen more than sevenfold, overdiagnosis was also excluded as the explanation. The authors conclude that the rising incidence of esophageal adenocarcinoma represents a real increase in disease burden.
Designing SELECT
The Selenium and Vitamin E Cancer Prevention Trial (SELECT) was planned as a phase III randomized, placebo-controlled trial of selenium and/or vitamin E supplementation for a minimum of 7 years to study possible agents for the prevention of prostate cancer in a population of 32,400 men in the United States, including Puerto Rico, and Canada. Prostate cancer continues to be a major health threat, and SELECT recruited non-African American men at least 55 years of age and African American men, who have the world's highest risk of this disease, at least 50 years of age. Lippman et al. (p. 94) discuss the problems that had to be resolved in developing a large trial that conforms as closely as possible with community standards of care. These problems included the role of screening with prostate-specific antigen and/or digital rectal examination, the best forms and doses of the study agents, and estimating the rate of prostate cancer among men on the placebo arm.
Epigenetic Changes in Prostate Cancer
Epigenetic changes that modify DNA and histones, respectively, may have profound effects on cancer development and progression. Li et al. (p. 103) review the current literature on changes in DNA methylation status and histone modifications as they pertain to prostate cancer. The authors also discuss the interactions between the two classes of epigenetic changes and how, because of the reversibility of the changes, they may be exploited to understand the pathogenesis of prostate cancer, to identify potential tumor biomarkers for early diagnosis and risk assessment of prostate cancer, and to design potential therapeutic strategies.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||