© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 21, 1789,
November 3, 1999
© 1999 Oxford University Press
IN THIS ISSUE |
Tamoxifen treatment has been shown in a randomized placebo-controlled trial to reduce substantially the risk of invasive breast cancer in a population of women at elevated risk. However, tamoxifen treatment is associated with some health-related risks, e.g., endometrial cancer, stroke, pulmonary embolism, and deep vein thrombosis. Gail et al. (p. 1829) have developed tools to assist in counseling women about the use of tamoxifen and in weighing the risks and benefits of treatment with this drug. They find that the risks and benefits of tamoxifen depend on age and race, as well as on a woman's specific risk factors for breast cancer. The risks increase with age, and the risks of some events differ between white women and black women. The investigators conclude that tamoxifen is most beneficial for younger women with an elevated risk of breast cancer.
In an editorial, Taylor et al. (p. 1792) note that risk/benefit assessment of any therapeutic tool is an extremely important process and that the efforts of Gail et al. are commendable. The editorial writers point out, however, that the information developed cannot be used with confidence in African-American women because of their under-representation in the clinical trial used in this study. Taylor et al. posit that aggressive recruitment of minorities in major clinical trials is imperative so that questions of drug efficacy in minority populations do not remain at the conclusion of otherwise definitive trials.
Counseling Adolescents About Smoking
Thorndike et al. (p. 1857) analyzed data from the National Ambulatory Medical Care Surveys to assess the prevalence and predictors of physician identification, during office visits, of adolescent smoking status and physician counseling of youths about smoking. In surveys conducted from 1991 through 1996, the investigators determined that physicians inquired into the smoking status of adolescents in approximately 70% of office visits; however, doctors provided smoking counseling in less than 2% of all visits and in less than 17% of visits by adolescents who were identified as smokers. Adolescents attended by primary care physicians and those diagnosed with conditions potentially complicated by smoking were more likely to have their smoking status identified and receive counseling. Younger and nonwhite adolescents were less likely to be counseled than adolescents who were older and white. The authors conclude that physicians treating adolescents are missing opportunities to discourage tobacco use among youths.
In an editorial, Lando and Hatsukami (p. 1795) state that the overall results of this study are discouraging, especially given the efforts in recent years to educate practicing physicians to identify and treat smokers, to develop evidence-based guidelines for smoking cessation treatment, and to encourage the development of systems to identify smokers.
DNA Alterations in Lung Cancer
Park et al. (p. 1863) have investigated the frequency, size, and patterns of molecularly abnormal clonal patches of cells in the bronchial epithelium of patients with lung cancer. They used 12 microsatellite DNA markers at seven chromosomal regions frequently deleted in lung cancer. Through polymerase chain reaction they evaluated microdissected samples (foci) of histologically normal and abnormal bronchial epithelium, as well as tumor tissue, from 19 patients with surgically resected lung carcinoma. They conclude that multiple small clonal patches of cells with molecular abnormalities are present in the nonmalignant bronchial epithelium of patients with lung cancer and that most of these clonal patches are relatively small in size (approximately 90,000 cells). They note that, in a given individual, the tumor appeared homogeneous with respect to molecular changes, but the clonally altered patches of mildly abnormal epithelium were heterogeneous.
In an accompanying editorial, Hittelman (p. 1796) points out that these results have taken the analysis of normal and histologically altered lung epithelium to an even more detailed level and provided more details of tumorigenesis. If the risk of developing lung cancer is related to the individual's exposure and inherent susceptibility to carcinogens, then a surrogate measure of total accumulated damage might provide useful information for assessing risk. The author proposes that such a surrogate measure could be the assessment of the degree of subclonal outgrowth of mutated cells in tissue obtained from random biopsies of bronchial epithelial tissue, as described by Park et al.
Fenretinide and Prevention
Fenretinide, a vitamin A analogue, has been shown in preclinical studies to inhibit breast carcinogenesis. Veronesi et al. (p. 1847) have investigated the efficacy of fenretinide in preventing second breast malignancies in women with breast cancer. In a randomized, phase III trial, 2972 women, aged 30-70 years, with surgically removed stage I breast cancer or ductal carcinoma in situ, either received fenretinide orally for 5 years or received no systemic treatment. The primary end points in the trial were the incidences of contralateral breast cancer and ipsilateral breast cancer 7 years after randomization. These outcomes were also analyzed post hoc after taking menopausal status and other factors into account. At a median observation time of 97 months, there were no statistically significant differences between the two study arms in contralateral and ipsilateral breast cancer incidence; however, a possible benefit was detected in premenopausal women with respect to these two outcomes.
In an editorial, Piantadosi (p. 1794) questions whether the post-hoc findings, that premenopausal women possibly benefited from the treatment, are due to chance and whether there is any biologic evidence corroborating these findings.
PTEN, Integrins, and Cancer
The extracellular matrix in which cells reside exerts profound control over cells. This regulation is often mediated by integrins, cell surface receptors that transmit a variety of biological signals. Many integrin signals affect cell cycle regulation, growth control, or apoptosis (programmed cell death) and thus play a role in the biology of cancers. Tamura et al. (p. 1820) present a comprehensive review of the regulation of the complex integrin signaling pathways by the tumor suppressor PTEN, which is mutated in a wide range of human cancers. PTEN regulates cell interactions with the extracellular matrix and maintains cell sensitivity to apoptosis. The authors conclude that elucidation of the novel regulatory pathways of integrin signaling may lead to new approaches to cancer therapy.
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