© 2003 by Oxford University Press
Journal of the National Cancer Institute, Vol. 95, No. 6, 417,
March 19, 2003
© 2003 Oxford University Press
IN THIS ISSUE |
Short-interval follow-up is recommended in up to 11% of screening mammograms that yield "probably-benign" findings. However, the predictive value of this recommendation for breast cancer is unclear. In a longitudinal analysis of 68,126 postmenopausal women, Yasmeen et al. (p. 429) found that 5% of the eligible women had baseline mammograms that included recommendations for short-interval follow-up. The incidence of breast cancer for women with this recommendation was 1.0% at 2 years after the baseline mammogram, compared with breast cancer incidence rates of 0.6% and 0.5% for women whose baseline mammograms were described as benign and negative, respectively. The authors conclude that having a mammographic recommendation for short-interval follow-up was associated with a low positive predictive value for breast cancer among postmenopausal women during a 2-year follow-up. They suggest that the current criteria for this recommendation—repeat mammography within 6 months—should be reconsidered.
In an editorial, Kerlikowske and colleagues (p. 418) review the empiric observations that led to the creation of the short-interval follow-up recommendation and how the American College of Radiology intended that recommendation to be used by radiologists. They note that the potential impact of Yasmeen et al.’s finding is limited because they did not have information on the initial and final mammography assessments or the diagnostic work-ups that led to short-interval follow-up recommendations for the women in their study.
Interferon Alpha, VEGF, and Tumor Angiogenesis
Interferon alpha (IFN-
) has antiangiogenic activity, although the underlying mechanism of action is unclear. Because human neuroendocrine (NE) tumors are highly vascularized and sensitive to IFN-, von Marschall et al. (p. 437) investigated whether the therapeutic effects of IFN- result from an inhibition of angiogenesis mediated by a decrease in vascular endothelial growth factor (VEGF) gene expression. The authors found that NE tumors and cell lines expressed VEGF mRNA and secreted VEGF protein. In vitro, IFN- decreased transcription of VEGF gene expression and VEGF protein levels. In vivo, IFN- inhibited xenograft tumor growth and reduced microvessel density, a measure of angiogenesis. Patients with NE tumors had lower VEGF plasma levels and reduced VEGF mRNA levels and microvessel density in liver metastasis biopsy material after IFN- treatment. The authors concluded that IFN- confers its antitumor activity, at least in part, by its antiangiogenic activity.
In an editorial, Tosato (p. 420) discusses the novel finding that IFN- directly regulates VEGF expression within the historical context of tumor angiogenesis.
Early-Onset Breast Cancer and BRCA Mutations
Women with a family history of breast cancer, especially of early-onset breast cancer, have an increased risk of breast cancer. Because little is know about specific causes of this association, Dite et al. (p. 448) studied the mothers, sisters, and aunts of case patients diagnosed with breast cancer before age 60 years, and conducted extensive BRCA1 and BRCA2 mutation testing in case patients diagnosed before age 40. Among the greater than expected number of breast cancers attributed to familial factors in relatives of women diagnosed before age 40, less than one third of those breast cancers were related to mutations in BRCA1 or BRCA2. They conclude that mutations in genes other than BRCA1 and BRCA2 may be associated with a high risk of breast cancer in young women.
PDFG-R Phosphorylation and Prostate Cancer Bone Metastases
Expression of platelet-derived growth factor (PDGF) and autophosphorylation of its receptor (PDGF-R) are associated with the growth of metastatic prostate tumor cells in bone. STI571 blocks the PDGF signaling pathway by inhibiting PDGF-R autophosphorylation. Uehara et al. (p. 458) examined the effects of STI571, given alone or with paclitaxel, on the growth of human prostate cancer PC-3MM2 cells injected into the tibias of nude mice. Mice treated with STI571 or STI571 plus paclitaxel had a lower tumor incidence, smaller tumors, and less bone lysis and lymph node metastasis than control or paclitaxel-treated mice. Mice treated with STI571 or STI571 plus paclitaxel had less phosphorylated PDGF-R on tumor cells and tumor-associated endothelial cells than control mice. The authors conclude that endothelial cells appear to express phosphorylated PDGF-R when they are exposed to tumor cells that express PDGF and that STI571, especially in combination with paclitaxel, may produce substantial therapeutic effects against prostate cancer bone metastasis.
Lung Cancer Risk Prediction
Although smokers and former smokers are at high risk of lung cancer, the ability to determine an individual smoker’s absolute risk of the disease would be useful from the perspective of both patient care (e.g., an individual could make a better-informed decision about screening) and clinical research (e.g., researchers could target the highest-risk individuals for prevention studies). In this issue, Bach and colleagues (p. 470) describe a lung cancer risk prediction model derived from data on more than 18 000 subjects enrolled in CARET, a randomized trial of lung cancer prevention. The risk predictors included age, sex, asbestos exposure history, and several smoking history parameters. Several tests showed that the model was internally valid and well calibrated. When the authors applied the model to smokers enrolled in a study of lung cancer screening, they found wide variations in 10-year lung cancer risk, from as low as 0.8% to as high as 15%.
Parity and Breast Cancer Risk in Black Women
In the United States, breast cancer incidence is higher among African-American women than among white women before age 45 but lower at older ages. To explore whether differences in childbearing patterns can explain this observation, Palmer et al. (p. 478) assessed the relationship of several childbearing variables to breast cancer risk in the Black Women’s Health Study, a large prospective cohort study of U.S. African-American women. The authors found that parity has a dual association with breast cancer risk in African-American women; among women younger than 45, parity is associated with an increased breast cancer risk, and among women 45 or older it is associated with a decreased breast cancer risk. They conclude that the dual effect may explain some of the observed differences in breast cancer incidence rates among African-American and white women.
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