© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 4, 297,
February 17, 1999
© 1999 Oxford University Press
IN THIS ISSUE |
Axillary lymph node dissection is an established component of the surgical treatment of breast cancer, and it is an important procedure in cancer staging; however, it is associated with unpleasant side effects. In a study involving 376 patients, Veronesi et al. (p. 368) have investigated a radioactive tracer-guided procedure to identify the sentinel lymph node (i.e., the node first receiving lymph from the area of the breast containing the tumor) so that it could be removed and examined as a means of predicting the status of the axilla. The procedure identified the sentinel node in 98.7% (371) of the patients, and for 96.8% of that subset, the status of the node accurately predicted the status of the axilla. The investigators recommend a randomized trial to determine whether axillary dissection can safely be avoided in those patients with an uninvolved sentinel lymph node.
In an accompanying editorial, Krag (p. 302) makes reference to a multicenter study of sentinel node biopsy in patients with breast cancer, where the results show that 3% of all patients with positive lymph nodes had affected nodes exclusively outside the axilla. He points out that this pertinent assessment was unavailable from the Milan study. He concludes that the Milan study adds to the increasing body of evidence supporting removal of sentinel nodes by minimally invasive procedures to gain valuable information on the status of tumor metastasis.
Tumor Cells in Bronchoalveolar Lavage Fluids
Examination of sputum for tumor cells is an insensitive test in the diagnosis of non-small-cell lung cancer; however, molecular techniques have allowed detection of tumor-specific oncogene mutations in apparently normal (i.e., cytologically normal) sputum before the diagnosis of cancer. In an attempt to improve the diagnostic sensitivity of the molecular approach, Ahrendt et al. (p. 332) have used a battery of four polymerase chain reaction-based methods to detect lung cancer cells in bronchoalveolar lavage fluids from patients with early stage lung cancer. These methods detect tumor-specific mutations in the p53 and K-ras genes, allow determination of the methylation status of the CpG island of the p16 gene, and analyze microsatellite DNA instability by use of a panel of 15 marker sequences. The authors report that, when all four assays were used, molecular alterations were detected in the bronchoalveolar lavage fluids of 53% of patients whose resectable tumors carried a genetic alteration.
In an editorial, Gazdar and Minna (p. 299) discuss currently available tests for the detection of lung cancer and put the results of Ahrendt et al. into perspective. They conclude that the findings of Ahrendt et al. should provide the stimulus for further advances in molecular techniques to detect lung cancer. However, they point out that, given the state of evidence, we still have to wait before we can use molecular screening as a clinical tool.
X-Chromosome Inactivation and Heritable Ovarian Cancer
Most human female cells contain two X chromosomes, only one of which is active. Since either X chromosome can be inactivated during development, tissues are produced that usually contain equal numbers of cells with active X chromosomes of either maternal or paternal origin. However, nonrandom inactivation can occur in a subset of females. If a tumor suppressor gene were located on the X chromosome and if females with a germline mutation in one copy of that suppressor gene experienced nonrandom X-chromosome inactivation, then some or all of the tissues of such women might lack the wild-type suppressor gene function, predisposing them to develop cancer. Buller et al. (p. 339) have investigated this possibility for the development of hereditary ovarian cancer. The authors present evidence that nonrandom X-chromosome inactivation may be a predisposing factor in the development of invasive, but not borderline, ovarian cancer.
In an editorial, Brown (p. 304) remarked that females with a germline suppressor gene mutation and with or without random X-chromosome inactivation can have increased susceptibility to cancer. She further pointed out that nonrandom X-chromosome inactivation and elevated cancer risk could be consequences of one event or of independent events. She cautioned that other factors, such as the size of the pool of cells undergoing X-chromosome inactivation, can influence this assessment.
Oltipraz and Metabolism of Aflatoxin B
Liver cancer is the leading cause of cancer death in Qidong, a city in eastern Jiangsu Province, People's Republic of China. It has been postulated that chronic hepatitis B virus infection and dietary exposure to aflatoxins contribute to the extraordinarily high risk of liver cancer in this city. Since the drug oltipraz has been shown to afford complete protection against aflatoxin-induced liver cancer in rats, Wang et al. (p. 347) are investigating whether oltipraz might be an effective chemopreventive agent in humans. The authors report findings from a randomized, placebo-controlled, double-blind, phase IIa study in which 240 residents of Qidong received either one of two doses of oltipraz or placebo daily for 8 weeks. Wang et al. report that oltipraz modulates the metabolism of aflatoxin B1 in humans in two ways, both of which would reduce the carcinogenic potential of this food contaminant.
Retinoids and Chemoprevention
Retinoids, which are natural and synthetic derivatives of vitamin A, and ß-carotene, a
related compound, have been investigated as chemoprevention agents in individuals at high risk
of developing cancer. Although retinoids have been shown to reduce the incidence of some types
of second cancers in patients treated for an initial cancer, ß-carotene has been shown to be
ineffective in preventing lung cancer in high-risk individuals. To further understand why some
vitamin A-related compounds are effective and others are not, Boyle et al. (p. 373) have investigated one proposed mechanism by which retinoids might exert their
beneficial chemoprevention effects. The authors report that certain retinoids, but not
ß-carotene or 
-carotene, induce the degradation of cyclin D1 protein in normal,
immortalized, and carcinogen-transformed human bronchial epithelial cells in vitro,
thereby leading to a suppression of cellular proliferation.
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