African-American women who give birth to four or more children appear to be at an increased risk of breast cancer before the age of 45, according to a new study in the March 19 issue of the Journal of the National Cancer Institute. However, the same study found that African-American women who give birth to four or more children have a decreased risk of developing breast cancer at age 45 or older. "These results may shed light on the puzzling differences in breast cancer incidence rates for African-American and white U.S. women," notes lead author Julie R. Palmer, Sc.D., of Boston University, and her colleagues. They point out that, 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. The study involved 56,725 women who were participating in the Black Women's Health Study. Contact: Gina Digravio, Boston University, 617-638-8491, gina.digravio@bmc.org
Drug Inhibits Growth of Metastatic Prostate Cancer in Bone
STI571 (imatinib mesylate, Gleevec), especially in combination with paclitaxel (Taxol), may be effective in controlling the spread, or metastasis, of prostate cancer to the bone, according to a new study in the March 19 issue of the Journal of the National Cancer Institute. Hisanori Uehara, M.D., Isaiah J. Fidler, D.V.M., Ph.D., and their colleagues at M. D. Anderson Cancer Center in Houston examined human prostate cancer cells that were injected into the leg bones of mice that were then treated with STI571 alone, paclitaxel alone, STI571 plus paclitaxel, or water (as a control).
Compared with mice that received water, mice treated with STI571 plus paclitaxel had less phosphorylated platelet-derived growth factor receptor (PDGF-R) on tumor cells and more tumor cell death. Phosphorylated PDGF-R is associated with growth of metastatic prostate tumor cells in bone. Treatment with STI571 plus paclitaxel was also associated with a statistically significant inhibition of the growth of bone tumors and the preservation of bone structure. The authors conclude that "using STI571 to inhibit PDGF-R phosphorylation may, especially in combination with paclitaxel, produce substantial therapeutic effects against prostate cancer bone metastasis." Contact: Laura Sussman, University of Texas M. D. Anderson Cancer Center, 713-792-0655, lsussman@mdanderson.org
Risk of Lung Cancer Varies Widely Among Smokers
The risk of lung cancer varies widely among smokers, according to a new study in the March 19 issue of the Journal of the National Cancer Institute. Peter B. Bach, M.D., of the Memorial Sloan Kettering Cancer Center in New York, and his colleagues developed a lung cancer risk prediction model using data from 18,172 individuals enrolled in the Carotene and Retinol Efficacy Trial. 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. For example, a 51-year-old woman who smoked one pack per day for 28 years before quitting 9 years earlier has a ten year risk of less than 1%, compared to a 15% risk for a 68-year-old man who has smoked two packs per day for 50 years and continues to smoke. The authors say that accurate risk prediction may help individuals who are contemplating voluntary screening to balance the potential benefits and risks of screening. Risk prediction may also be useful for researchers designing clinical trials of lung cancer prevention, the authors say.
Contact: Joanne Nicholas, Memorial Sloan-Kettering Cancer Center, 212-639-3573, nicholaj@mskcc.org
non-BRCA Mutations May Play a Role in Familial Breast Cancer
Mutations in genes other than BRCA1 and BRCA2 may be associated with a high risk of breast cancer, particularly in younger women, according to a study in the March 19 issue of the Journal of the National Cancer Institute.
Women with a family history of breast cancer, especially of early-onset breast cancer, have an increased risk of the disease. Because little is know about specific causes of this association, Gillian S. Dite, B.Sc., and John L. Hopper, Ph.D., of the University of Melbourne, Australia, and colleagues studied the mothers, sisters, and aunts of patients diagnosed with breast cancer before age 60. They also conducted extensive BRCA1 and BRCA2 mutation testing in patients diagnosed with breast cancer before age 40.
The investigators calculated that the cumulative risk of breast cancer up to age 50 was 6, 3, and 2 times the risk in the general population among sisters, mothers, and aunts, respectively, of patients with breast cancer. However, less than one-third of the breast cancers in relatives of women diagnosed before age 40 were related to mutations in BRCA1 or BRCA2. "Familial and genetic aspects of susceptibility for breast cancer include more genes than BRCA1 and BRCA2, especially for disease in women diagnosed when younger than 40 years," the authors conclude.
Interferon Alpha Slows Angiogenesis by Regulating VEGF Expression
Interferon alpha (IFN-a) has antiangiogenic activity, but, until now, the underlying mechanism of action was unclear. According to a study in the March 19 issue of the Journal of the National Cancer Institute, IFN-a confers its antitumor activity, at least in part, by its antiangiogenic activity.
Because human neuroendocrine (NE) tumors are highly vascularized and sensitive to IFN-a, Zofia von Marschall, M.D., and Stefan Rosewicz, M.D., of Humboldt University, Berlin, and colleagues investigated whether the therapeutic effects of IFN-a result from an inhibition of angiogenesis mediated directly by a decrease in vascular endothelial growth factor (VEGF) gene expression. In vitro, IFN-a decreased transcription of VEGF gene expression and VEGF protein levels. In vivo, IFN-a 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 after IFN-a treatment.
Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage.
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JNCI Journal of the National Cancer Institute