© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 14, 1039,
July 17, 2002
© 2002 Oxford University Press
IN THIS ISSUE |
Whether postmenopausal women with lymph node-negative breast cancer should be given adjuvant chemotherapy is controversial. The International Breast Cancer Study Group (IBCSG) (p. 1054) launched a randomized trial to evaluate the role of adjuvant chemotherapy followed by tamoxifen compared with tamoxifen alone in 1669 postmenopausal women with lymph node-negative disease. The IBCSG found that the benefit of chemotherapy was statistically significantly dependent on the estrogen receptor (ER) status of the tumor. They found that patients with ER-negative tumors had substantially better survival with chemotherapy followed by tamoxifen than with tamoxifen alone. However, adding chemotherapy provided no benefit to patients with ER-positive cancer compared with tamoxifen alone.
In an editorial, Wolff and Abeloff (p. 1041) point out that, for daily practice, this trial confirms the benefit of a short course of chemotherapy for older women with lymph-node negative, endocrine-unresponsive disease but leaves unanswered its role in endocrine-responsive disease treated with tamoxifen.
Death and Cancer-Directed Surgeries
Cancer mortality should include deaths from cancer as well as from cancer treatment. Deaths within 30 days of a surgical procedure are considered treatment-related deaths in the calculation of surgery-related mortality. Welch and Black (p. 1066) determined how cause of death is attributed in patients diagnosed with one of 19 common solid tumors who die within 1 month of cancer-directed surgery using 1994–1998 SEER data. The authors found that the proportion of deaths not attributed to the coded cancer was 41%, ranging from 12% for cervical cancer to 81% for laryngeal cancer. They determined that if all deaths within 1 month of cancer-directed surgery were attributed to cancer, cancer mortality would rise about 1%. They conclude that this misclassification may indicate general confusion about how to code treatment-related deaths in cancer.
In an editorial, Begg and Schrag (p. 1044) discuss the limitations of classifying cancer as the underlying cause of death for all deaths within 1 month of cancer-directed surgery and identify some of the pitfalls associated with measurements of the impact of cancer on mortality.
New Diagnostic Marker for Bladder Cancer
Early detection and monitoring of patients with bladder cancer may be important for successful treatment. Cystoscopy, considered the gold standard diagnostic test for bladder cancer, is invasive and costly, and cytologic analysis of voided urine has low sensitivity. Stoeber et al. (p. 1071) used an immunofluorometric assay to measure levels of the DNA replication initiation factor minichromosome maintenance protein 5 (Mcm5) in urine sediments of patients with nonspecific lower urinary tract symptoms. All patients underwent cystoscopy shortly after producing the sample. The authors found that the Mcm5 test was more sensitive that urine cytology for detecting bladder cancers. They also found that patients with prostate cancer had higher Mcm5 levels than patients with no malignancy. The authors conclude that elevated levels of Mcm5 in urine sediments are highly predictive of bladder cancer.
Glucose Transporter 1 and Matrix Metalloproteinase 2
Cancer cells express higher levels of glucose transporter proteins (Gluts) than normal cells. Glut-1 overexpression is associated with invasiveness. Matrix metalloproteinase-2 (MMP-2) is also overexpressed in cancer cells and is associated with invasiveness. Ito et al. (p. 1080) tested the hypothesis that Glut-1 may regulate MMP-2 expression by transiently transfecting Glut-1 cDNA or Glut-1 antisense oligonucleotides in the human rhabdomyosarcoma cell line RD and analyzing MMP-2 mRNA expression and cell invasiveness. The authors found that changes in MMP-2 expression were positively associated with changes in Glut-1 expression. For example, increased Glut-1 expression was associated with increased MMP-2 expression and increased invasiveness, and suppression of Glut-1 expression was associated with decreased MMP-2 expression and invasiveness. The authors noted that this association between Glut-1 and MMP-2 expression was also tightly associated in human cancer cell lines and cancer tissues. The authors conclude that, because suppression of Glut-1 decreased MMP-2 expression and cancer cell invasion, Glut-1 could be a target for therapy of various cancers that overexpress Glut-1.
DNA Repair and Non-Small Cell Lung Cancer
Non-small cell lung cancer (NSCLC) is frequently resistant to chemotherapeutic agents, and this resistance has been associated with elevated nucleotide excision repair (NER) in tumor tissue. Bosken et al. (p. 1091) hypothesized that patients with genetically determined effective DNA repair capacity (DRC), an estimate of NER activity, would have poorer survival than patients with suboptimal DRC, and that the association between DRC effectiveness and survival would be most marked in patients receiving chemotherapy. The authors performed a retrospective analysis of DRC in 375 NSCLC patients and found that for every unit (%) increase in DRC the risk for death increased by approximately 5%. In a subset of 86 patients treated with chemotherapy only the risk for death increased by 11%, with those patients in the top quartile of the DRC distribution being at twice the risk for death than patients in the bottom quartile. The authors conclude that effective DRC may be a risk factor for poorer survival in NSCLC patients treated with chemotherapy.
Insulin-Like Growth Factor I Pathway and Prostate Cancer
To determine whether plasma levels of insulin-like growth factor I (IGF-I) and its binding protein IGFBP-3 predict more aggressive forms of prostate cancer, Chan et al. (p. 1099) investigated the association between plasma levels of each with specific stages and grades of prostate cancer in a prospective case–control study. They found that plasma levels of IGF-I and IGFBP-3 were predictors of advanced-stage prostate cancer but not of early-stage cancer. Combining these measurements with a standard prostate-specific antigen (PSA) test increased the specificity but decreased the sensitivity for detecting prostate cancer compared with a PSA test alone. The authors concluded that levels of IGF-I and IGFBP-3 may predict the risk of developing advanced-stage prostate cancer but their utility for identifying patients with incident cancer may be limited.
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