African American women face a greater risk of death from breast cancer, in part because they tend to be diagnosed at later stages of the disease than white women. New findings published online today in Cancer suggest that this disparity in stage of diagnosis can be reduced, using a program that pairs educational outreach to the community with patient navigators who advise and guide diagnosed patients.
Three years after the program was launched, a cross-sectional study of all breast cancer patients at the primary community hospital showed that the proportion of women diagnosed with in situ breast cancer doubled, while those diagnosed with stage IV breast cancer fell by more than a third.
The authors believe the results have "implications on prognosis, and ultimately outcome, for these women if recommended treatment guidelines are followed." They note that the cross-sectional study design could not definitively prove that the intervention caused the shift in stage of diagnosis they observed, but they are continuing prospective work to link the effect of CHAs and patient navigators to particular patient outcomes.
Osteopontin Helps Tumors Harness Bone Marrow Cells for Growth
Researchers at the Whitehead Institute for Biomedical Research and their colleagues have shown that the protein osteopontin, released by breast carcinoma cells, can induce the growth of distant, inactive tumors through the recruitment of bone marrow cells (BMCs). Their report appeared June 13 in Cell.
The investigators injected mice with an indolent (slow-growing) breast cancer cell line in one flank, and in the other flank they injected either one of two vigorously growing breast carcinoma lines for the test group or a placebo of matrigel, the liquid vehicle used to support cells for injection, for the control group.
Mice in the test group showed approximately 10 times the tumor growth in the indolent cells as control mice that received the placebo. The cause of the growth was not metastasis of the active cells to the indolent tumor site, but rather the recruitment of BMCs to tumors in both flanks, which in turn encouraged growth of the injected cells.
After analyzing the plasma levels of 80 known human cytokines, the investigators identified osteopontin as a necessary factor for recruitment of BMCs and subsequent tumor growth. Osteopontin is a glycoprotein involved in inflammation, angiogenesis, and metastasis, and has been found in higher levels in cancer patients with metastatic disease. However, when the researchers induced a cell line that does not normally express osteopontin to produce the protein, this alone was not sufficient to trigger tumor growth, indicating the involvement of other cellular factors.
LYN Kinase May Contribute to Imatinib Resistance in CML
Imatinib (Gleevec), the standard treatment for chronic myelogenous leukemia (CML), works by targeting a protein called BCR-ABL, which is expressed only in leukemia or lymphoma cells. Unfortunately, many patients eventually become resistant to treatment with imatinib, and their cancer progresses. Mutations in BCR-ABL that occur over time account for some but not all cases of imatinib resistance, and researchers believe that other proteins may play a role.
In a study published online today in the Journal of the National Cancer Institute, investigators from the University of Texas M.D. Anderson Cancer Center and colleagues showed that persistent activation of a protein called LYN kinase may be one of the factors involved in imatinib resistance, independent of any mutations found in BCR-ABL.
The investigators tested both established, BCR-ABL-mutation-negative CML cell lines and patients with BCR-ABL-mutation-negative CML. In patients and cells sensitive to imatinib treatment, the drug suppressed the overactivation of LYN kinase; however, in imatinib-resistant cells and patients, LYN kinase remained activated after imatinib treatment. When LYN kinase activity was reduced - with gene silencing in the cells or with the drug dasatinib in patients - the cells died and the patients responded to treatment.
Interestingly, in imatinib-sensitive cell lines and cells taken from patients, the activation of LYN kinase appeared to be regulated by BCR-ABL, but not in imatinib-resistant cells.
Although the investigators cautioned that their cell samples were small, thereby restricting their ability to perform repeat analyses, their results "support the presence of…complex mechanisms of targeted drug resistance in CML patients. The association and mechanism of LYN activation in imatinib resistance warrants further study in additional patients," they concluded.
Mortality Risks Highlight the Effect of Smoking
Charts published June 18 in the Journal of the National Cancer Institute compare side-by-side an individual's chances of dying within 10 years from various causes according to age, sex, and smoking status.
Earlier versions of these charts were published 5 years ago by the same NCI-supported researchers, who are affiliated with the U.S. Department of Veterans Affairs and institutions in Vermont and New Hampshire; the new charts include updated mortality data and a revised algorithm to calculate the risks.
For current smokers, former smokers, and those who have never smoked, the researchers calculated age-specific risk of death (number of cases per 1,000 people) from heart disease; stroke; lung, colon, or prostate cancer; pneumonia; flu; AIDS; chronic obstructive pulmonary disease; accidents; and all causes combined. They used data from the National Center for Health Statistics and the U.S. Census Bureau.
Among the most striking trends in the charts are the fact that men of all ages are more likely than women to die in the next 10 years, and that smoking has the detrimental effect of adding about 5 years to the age of a woman and 10 years to the age of a man.
The charts are meant to help clinicians and patients discuss health risks, note the authors. "[They] provide two basic elements that people need if they are to make sense of the health threats they face: the magnitude of the risk and some context…[to] help people understand where to focus risk reduction efforts." The charts may be especially useful in smoking prevention and cessation efforts, they add.
More information from NCI on quitting smoking can be found at http://www.smokefree.gov and from the toll-free tobacco quitline at 1-800-QUITNOW (784-8669).