© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 13, 961,
July 4, 2001
© 2001 Oxford University Press
IN THIS ISSUE |
Women who have been diagnosed with breast cancer have a two- to sixfold greater risk of developing contralateral breast cancer than women in the general population have of developing a first breast cancer. Tamoxifen therapy reduces a woman’s risk of developing contralateral breast cancer, but it is not known whether tamoxifen use affects the development of both estrogen receptor (ER)-positive and ER-negative contralateral tumors. Li et al. (p. 1008) used data from a population-based tumor registry to assess this relationship. The authors found that women treated with tamoxifen for a primary breast tumor had a relative risk of 0.8 of developing an ER-positive contralateral breast tumor and a relative risk of 4.9 of developing an ER-negative contralateral tumor. The authors conclude that tamoxifen use decreases the risk of ER-positive contralateral breast tumors, but it may increase the risk of ER-negative contralateral tumors.
In an accompanying editorial, Swain (p. 963) points out that the results reported by Li et al. are inconsistent with those obtained in several other published studies of tamoxifen use and contralateral breast cancer. She cautions that, because of its limitations, this study does not provide sufficient evidence upon which to guide clinical practice.
Retroviral Endostatin In Vivo
Although inhibiting tumor angiogenesis is an attractive strategy for treating cancer, development of the angiogenesis inhibitors has been hampered by problems with stability, manufacturing, and administration of recombinant antiangiogenic proteins. Feldman et al. (p. 1014) developed retroviral vectors containing the murine endostatin gene, infected the murine liver cell line NMuLi, and selected clones stably expressing different amounts of endostatin (NEF-Endo). The infected clones were grown as either subcutaneous or intraperitoneal tumors in nude mice. Although increased levels of endostatin were not detected in the serum of tumor-bearing mice, increased levels were detected in tumor lysates. Furthermore, the tumor volumes in mice with subcutaneous or intraperitoneal NEF-Endo tumors were statistically significantly lower than those generated from the parental cell line. The authors conclude that retroviral endostatin gene transfer leads to the secretion of functional endostatin that can inhibit both subcutaneous and intraperitoneal tumor growth.
In an editorial, Kleinman and Liau (p. 965) discuss the diversity and function of angiogenesis inhibitors, focusing on their role in tumor biology and the requirements for designing effective antiangiogenesis cancer therapies.
Consensus Statement: Adjuvant Therapy for Breast Cancer
As research on breast cancer treatment continues, patients now have more treatment options than ever before. The accepted primary treatments for localized breast cancer are breast-conserving surgery plus radiation therapy or mastectomy with or without breast reconstruction. Less agreement among clinicans exists regarding the use of adjuvant treatments, such as chemotherapy, hormonal therapy, and adjuvant radiation therapy. In November 2000, the National Institutes of Health convened a Consensus Development Panel to oversee the presentation, review, and summarization of current data on adjuvant therapy for breast cancer (p. 979). The panel presented a wide range of specific treatment recommendations, depending on such factors as hormone receptor status and disease stage. In addition, the panel identified a need for more data on the role of chemotherapy in treatment in women older than 70 years, on the use of radiotherapy in women with one to three tumor-positive lymph nodes, and on quality-of-life outcomes from adjuvant therapy.
4-HPR and Esophageal Tumorigenesis in Rats
N-(4-Hydroxyphenyl)retinamide (4-HPR) and 9-cis-retinoic acid (9-cis-RA) are potential chemopreventive agents for many epithelial tumors. Gupta et al. (p. 990) tested the effects of these agents on N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumorigenesis in rats, an animal model for human esophageal squamous cell carcinoma. The authors unexpectedly found that rats fed a diet containing 4-HPR developed more and larger esophageal tumors than rats fed a diet that lacked either agent. Rats fed a diet containing 9-cis-RA had no increase in tumor growth. Compared with rats fed the control diet, rats fed 4-HPR-containing diets had higher levels of O6-methylguanine adducts in their esophageal DNA and more CYP2A3 mRNA and higher levels of NMBA metabolites in their esophagi. The authors conclude that, in the rat esophagus, 4-HPR increases NMBA metabolism and enhances nitrosamine-induced carcinogenesis.
Recombinant Canarypox Viruses in a Prostate Cancer Model
Griffith et al. (p. 998) examined whether canarypox ALVAC viruses carrying immunostimulatory cytokine genes (ALVAC-cytokine) could induce antitumor immunity in the RM-1 model of a highly aggressive, weakly immunogenic murine prostate cancer. They found that, in mice, RM-1 cells infected with ALVAC-cytokine viruses elicited greater antitumor activity than RM-1 cells infected with the parental ALVAC viruses. They also observed that natural killer cells were necessary for the antitumor activity. However, tumor-specific regulatory T cells were also induced that inhibited tumor-specific cytotoxic T lymphocytes, resulting in a lack of immunity to subsequent tumor challenge. They report that studies are under way to determine the potential ramifications of activating such a regulatory cell population in patients with prostate cancer subjected to this type of tumor cell vaccination protocol.
Nasopharyngeal Radium Irradiation and Cancer Mortality
Nasopharyngeal radium irradiation (NRI) was used to treat eustachian tube dysfunction in children and middle ear barotrauma in aviators and submariners from the early 1940s to the mid-1960s. In a Dutch cohort study of more than 10,000 people, Ronckers et al. (p. 1021) assessed whether NRI-exposed individuals were at higher risk for cancer-related deaths than were nonexposed individuals. The authors found that NRI-exposed individuals were not at increased risk of cancer-related death from head and neck, brain, or thyroid cancers, and, in contrast with an earlier study, the authors found that NRI exposure was not associated with decreased risk of death from breast cancer. The authors state that definitive conclusions regarding the risk of cancer-related death in NRI-exposed individuals must await further follow-up.
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