© 2005 Oxford University Press
IN THIS ISSUE
Update on Tamoxifen for Breast Cancer PreventionThe National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention study (P-1) was initiated in 1992 to investigate whether tamoxifen could prevent the development of breast cancer in women at high risk for the disease. In 1998, it was reported that women who received tamoxifen had a lower risk of breast cancer than women who received placebo; they also had a reduced risk of osteoporotic fractures and increased risks of endometrial cancer, thromboembolism, and several other undesirable side effects. In this issue, Fisher et al. (p. 1652) present updated findings from P-1. After 7 years of follow-up, women who received tamoxifen had a 43% lower cumulative rate of invasive breast cancer, a 37% lower rate of noninvasive breast cancer, and a 32% lower rate of osteoporotic fractures—reductions similar to those seen in the original report of P-1. Relative risks of other treatment effects, both beneficial and undesirable, were also similar to those initially reported. The results of the follow- up, the authors conclude, clearly identify cohorts of women that derived a net benefit from receiving the drug.
Retinoid Resistance and Lung Carcinogenesis
To determine whether promoter methylation inhibits retinoic acid receptor (RAR) 
expression in human bronchial epithelial cells, Petty et al. (p. 1645) analyzed the RAR P2 promoter in all-trans-retinoic acid (RA)–sensitive and –resistant forms of the cells. The authors observed that the RAR P2 promoter was hypermethylated only in the RA-resistant cells and, in the process, they also identified a novel RAR isoform that they designated RAR1'. They observed that RAR1' was not expressed in RA-resistant human bronchial epithelial cells or in lung cancer tissues. However, lung cancer cells that were engineered to express RAR1' that were treated with RA grew more slowly and had increased expression of RA-dependent genes compared with untreated cells. The authors conclude that RAR1' expression may overcome retinoid resistance in lung carcinogenesis.
In a related editorial, Sabichi et al. (p. 1632) discuss the problem of retinoid resistance in lung cancer and the complexity of retinoic acid receptor function in normal and malignant cells. They note that the findings of Petty et al. may renew interest and bring new strategies to this area of chemoprevention research.
Vaccination With Cetuximab Mimotopes
Repeated administration of the monoclonal antibody cetuximab (IMC-225, Erbitux) inhibits epidermal growth factor receptor (EGFR) signaling. Riemer et al. (p. 1663) examined whether a vaccine using the mimotope approach could be generated and whether vaccination with the cetuximab mimotope could induce the continuous production of cetuximab-like antibodies in mice. They found that mimotope-induced antibodies exert antitumor activities and that the antibodies elicited both antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity and EGFR internalization into endocytic vesicles. They also report that the induced antibodies inhibited growth of EGFR-expressing cells to a similar extent as cetuximab. The authors conclude that epitope-specific immunization is feasible in mice and that the mimotope-induced antibodies have similar biologic properties to those of the monoclonal antibody cetuximab.
Lifetime Recreational Exercise and Breast Cancer Risk
Although physical inactivity is a potentially modifiable breast cancer risk factor, there is little information about this relationship for black women. Bernstein et al. (p. 1671) examined this relationship among white women and black women. They found that, among all women, decreased breast cancer risk was associated with increased levels of lifetime exercise activity. This inverse association did not differ between black and white women. They also noted that no modification of risk was observed by disease stage, estrogen receptor status, or any breast cancer risk factor other than history of breast cancer in a first-degree family member. They conclude that their study supports an inverse association between physical activity and breast cancer among black women and white women.
Diabetes Mellitus and Risk of Colorectal Cancer
Most, but not all, studies of diabetes and colorectal cancer risk have found a positive association. The findings have also been inconclusive with regard to sex and colorectal subsite. To resolve these inconsistencies, Larsson et al. (p. 1679) conducted a meta-analysis of published data on the association between diabetes and the incidence and mortality of colorectal cancer. They found that having diabetes was associated with an increased risk of colorectal cancer, compared with not having diabetes. These results were consistent between case–control and cohort studies and between studies conducted in the United States and Europe. They found that the association between diabetes and colorectal cancer incidence did not differ by sex or by cancer subsite. Diabetes was also positively associated with colorectal cancer mortality, but there was some heterogeneity among studies. They conclude that their results support a relationship between diabetes and an increased risk of colorectal cancer.
Deguelin and Tobacco-Induced Lung Tumorigenesis
Deguelin is a natural plant product that inhibits the proliferation of premalignant and malignant human bronchial epithelial cells by inhibiting Akt activation. To determine whether deguelin could block tobacco-induced lung tumorigenesis, which also occurs through Akt activation, Lee et al. (p. 1695) used a mouse model of tobacco-induced lung carcinogenesis and microcomputed tomography image analysis to monitor tumor size and number in vivo. Deguelin decreased Akt activation and the number of tobacco-induced lung tumors in the treated mice compared with untreated mice with no detectable toxicity. The authors conclude that deguelin should be considered for testing as a chemopreventive agent for early stages of lung carcinogenesis.
In a related editorial, Hecht (p. 1634) discusses previous studies using this model, points out the difficulties in designing mouse models of tobacco-induced lung carcinogenesis that are applicable to current and former smokers, and highlights the strengths and weaknesses of the study by Lee et al. He stresses the importance of chemoprevention for those who have quit smoking and for those who cannot.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||