News From The Journal Of The National Cancer Institute, April 28 2009
Researchers describe the rationale and a possible design for randomized controlled trials that test the impact of physical activity and weight control on breast cancer risk.
There are substantial observational data suggesting that regular physical activity and maintaining a healthy weight are associated with a reduction in breast cancer risk: however, it is unclear whether the apparent association is due to unknown confounding factors. An important way to determine if the lifestyle choices have a causal relationship with breast cancer risk is to test the hypothesis in the setting of a randomized controlled trial.
In the current commentary, Rachel Ballard-Barbash, M.D., of the National Cancer Institute in Bethesda, Md., and colleagues present designs for two trials, one in women who are at high risk of disease and one in breast cancer survivors. The interventions in the two trials could be the same; the goal for the weight control intervention would be a 10% weight loss for women with a body mass index above 25 kg/m2 at enrollment and avoidance of weight gain for those below 25 kg/m2. The goal for the physical activity intervention would be to achieve and maintain 150-220 minutes of physical activity per week.
"In conclusion, given the magnitude of the public health prob¬lem and the amount of accumulated evidence in support for this next level of scientific evidence, it is now appropriate to explore in detail the feasibility and timing of a large randomized trial to assess the effects of physical activity and weight control on breast cancer risk and/or prognosis - and the trade-offs in moving toward the prevention vs the survival trial," the authors write.
Clusterin Acts as a Tumor Suppressor Gene in Mouse Models of Neuroblastoma
Reduced expression of clusterin in a mouse model of neuroblastoma led to an increased number of tumors compared with control animals.
The role of clusterin in cancer has been unclear. Clusterin may affect processes related to cancer, including programmed cell death, motility, and inflammation.
In the current study, Arturo Sala, Ph.D., of the University College London Institute of Child Health, and colleagues used molecular techniques to increase or decrease expression of clusterin, MYCN, and a group of microRNAs named miR-17-19. MYCN and miR-17-19 microRNAs may regulate clusterin. The researchers assessed the impact of these changes in neuroblastoma cell lines and in animal models of neuroblastoma.
Increased expression of MYCN and miR-17-19 appeared to decrease the expression of clusterin, which was associated with increased tumor growth and metastasis. Increased clusterin expression was associated with reduced tumor growth and metastasis.
"We have provided, to our knowledge, the first evidence to show that clusterin is a tumor suppressor gene that is negatively regulated by the proto-oncogene MYCN," the authors write. "Mice with a disrupted clusterin gene developed more neuroblastomas than mice with a normal clusterin gene."
Gene Expression Ratio Test Predicts Outcome in Mesothelioma Patients Treated with Surgery
A four-gene expression ratio test prospectively distinguished mesothelioma patients who had a statistically significant longer overall survival from those who had shorter survival in a single-institution study.
There are few effective treatment options available for patients with malignant pleural mesothelioma other than surgery. However, not all patients appear to derive benefit from surgery. Raphael Bueno, M.D., of the Brigham and Women's Hospital in Boston and colleagues showed in retrospective studies that measuring expression ratios of four genes could distinguish between those who have a good prognosis after surgery and those who have a poor prognosis.
In the current study, Bueno and colleagues tested the four-gene expression ratio test in 120 patients with mesothelioma who were treated at Brigham and Women's Hospital and participated in a prospective clinical trial. To evaluate the robustness and reproducibility of the test, the researchers evaluated the test on multiple tumor samples from each patient and used two different microarray platforms and two different biopsy techniques.
The test was able to predict overall survival after adjusting for other clinical factors. The test results were consistent for individual patients regardless of the techniques used for the test. When the researchers combined the gene ratio test results with known prognostic factors, they were able to separate patients into high-risk and low-risk groups. The median survival for patients in the high-risk group was 6.9 months compared with 31.9 months in the low-risk group.
"Patients whose gene ratio test results predict a good prognosis after surgery may more confidently select the treatment option that includes surgery," the authors write.
Adult Survivors of Childhood Cancer Do Not Opt for Abortions More Frequently Than Their Healthy Sisters
Adult female survivors of childhood cancer do not opt for abortions more frequently than their sisters, according to data from a large Danish cohort study.
Previous studies suggested that women who had a childhood cancer may be concerned about the risks of having children and may choose to terminate a pregnancy more frequently than other women in the population.
In the current study, Jeanette Falck Winther, M.D., of the Danish Cancer Society in Copenhagen, and colleagues compared the proportion of pregnancies that ended in an induced abortion in 1,688 adult survivors of pediatric cancer who were included in the Danish Cancer Registry, in 2,737 of their sisters who did not have pediatric cancer, and in 16,700 women randomly selected from the Danish Central Population Register.
Cancer survivors chose to have an induced abortion in 19.7% of their pregnancies, which was similar to the proportion of pregnancies terminated by their sisters (18.9%) and by women in the general population (19.7%).
Although Danish records do not track a woman's reason for a first-trimester abortion, the reason for a second trimester abortion is recorded. "Survivors were not more likely than sisters and population control subjects to elect a second-trimester abortion because of physical and mental conditions or fetal abnormalities," the authors conclude.
Journal of the National Cancer Institute