Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Dec 2001
Review Multicenter StudyEarly lung cancer action project: annual screening using single-slice helical CT.
The advent of helical CT imaging held promise for the early diagnosis, and thereby, for enhanced curability of lung cancer--a highly fatal disease. In 1993, the Early Lung Cancer Action Project (ELCAP) was initiated and experimentally screened a cohort of 1,000 high-risk persons. ⋯ CT-based screening (compared to traditional radiology) was clearly shown to enhance the detection of lung cancer at earlier and more curable stages. A discussion follows of the meaning of the results and possible future screening protocols.
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Ann. N. Y. Acad. Sci. · Dec 2001
ReviewBeyond tamoxifen new endpoints for breast cancer chemoprevention, new drugs for breast cancer prevention.
Although tamoxifen appears to markedly reduce breast cancer risk in women with a prior diagnosis of atypical hyperplasia or in situ carcinoma, it is not clear what other groups of women receive substantial benefit. Major breast chemoprevention priorities are to (1) develop new agents that (a) have fewer side effects, (b) are effective in ER--as well as tamoxifen-resistant precancerous tissue, and (c) are compatible with hormone therapy; and (2) develop efficient clinical strategies including prognostic and predictive morphologic and molecular biomarkers. Breast tissue may be repeatedly sampled for evidence of intraepithelial neoplasia by fine needle aspiration, ductal lavage, or needle biopsy to select candidates at highest short-term risk as well as to monitor response in small proof of principle studies prior to a large cancer incidence trial. ⋯ Retinoids, rexinoids, and deltanoids may be efficacious in ER+ tissue resistant to tamoxifen. Agents which should theoretically have activity in ER- or ER+ precancerous tissue include polyamine synthesis inhibitors, tyrosine kinase inhibitors, combined demethylating agents and histone deacetylase inhibitors, as well as metalloprotease and angiogenesis inhibitors. Sample Phase I and Phase II clinical trial designs are reviewed using modulation of molecular markers and breast intraepithelial neoplasia as the major endpoints.
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West Nile virus, first isolated in 1937, is among the earliest arthropod-borne viruses discovered by humans. Its broad geographical distribution, not uncommon infection of humans, transmission by mosquitoes, and association with wild birds as enzootic hosts were well documented by the mid-1960s. However, West Nile virus was not considered to be a significant human pathogen because most infections appeared to result in asymptomatic or only mild febrile disease. ⋯ In addition the epidemic in the northeastern United States was unusual in the association of West Nile virus infection with fatal disease of birds, suggesting a change in the virulence of the virus toward this host. Understanding the risk factors that contributed to these three urban epidemics is important for minimizing the potential for future occurrences. This review will attempt to compare observations on the biology of West Nile virus made over about 60 years prior to the recent epidemics to observations made in association with these urban epidemics.
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Ann. N. Y. Acad. Sci. · Dec 2001
ReviewBreast cancer prevention with selective estrogen receptor modulators: a perspective.
Chemoprevention for breast cancer is both old and new. It has long been appreciated that early ovarian ablation dramatically reduces the incidence of breast cancer in premenopausal women. It was subsequently demonstrated, in the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) overview, that tamoxifen results in a 40% or greater reduction in the incidence of contralateral breast cancer. ⋯ Raloxifene, a newer selective estrogen receptor modulator (SERM) originally developed for osteoporosis, also appears to have a major preventive effect on breast cancer incidence. Limitations in the design and patient population of raloxifene trials, however, have made it difficult to as yet recommend raloxifene for risk reduction of breast cancer. The randomized Study of Tamoxifen and Raloxifene (STAR) study, which will compare raloxifene to tamoxifen in over 20,000 postmenopausal women at increased risk of breast cancer, as well as ongoing and proposed placebo-controlled studies of tamoxifen, the aromatase inhibitor anastrazole, and other antiestrogens in high- or average-risk postmenopausal women, will provide further results on optimal prevention strategies.
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Ann. N. Y. Acad. Sci. · Dec 2001
Comparative StudyThe MORE trial: multiple outcomes for raloxifene evaluation--breast cancer as a secondary end point: implications for prevention.
Breast cancer is a common disease in the United States and Europe and is therefore a major target for prevention strategies. Estrogen plays a central role in its pathogenesis, and treatment with estrogen deprivation has long been recognized to be an effective therapy. Tamoxifen is the first selective estrogen receptor modulator (SERM) to be widely used for the treatment of breast cancer and has been demonstrated to reduce the risk of breast cancer in high-risk women. ⋯ A second large-scale prevention trial in breast cancer comparing tamoxifen to raloxifene is presently enrolling cancer-free, but high-risk postmenopausal women (the STAR trial). Future directions include combined estrogen blockade of the breast by the addition of an aromatase inhibitor to a SERM. New trial designs, including those based on biochemical changes at the tissue level, will be required to allow future progress in this field with adequate rapidity.