People who are genetically predisposed to certain types of cancer can undergo treatments and surgeries that might reduce their risk of disease. For example, women who carry a mutation of the BRCA1 or BRCA2 genes are genetically predisposed to breast or ovarian cancer and can undergo tubal ligation or prophylactic mastectomy. Research on the effectiveness of interventions such as these can influence what physicians recommend and what individuals ultimately decide to do. In a commentary in the August 18 Journal of the National Cancer Institute, Dr. Sholom Wacholder of NCI warns that some of these studies may be susceptible to a bias that can misrepresent the effectiveness of the interventions.
Clinics that care for people at high risk for cancer provide a prime setting to study an intervention's efficacy because these clinics see a large number of patients who are carriers of mutated genes. Patients with these mutations who have been diagnosed with cancer typically serve as the study group; those who are carriers but have not developed cancer may be part of the study's control group.
In some studies, controls are recruited only from these high-risk clinics while study group patients are sometimes recruited from sources other than high-risk clinics to increase the number of such patients. As a result, those who were not diagnosed with cancer but previously seen at the clinic - the control group - may be more likely than the study group to have received an intervention. This discrepancy between groups, Dr. Wacholder points out, might cause the study to falsely conclude that the controls' lack of disease is a result of the intervention's effectiveness. Dr. Wacholder recommends that researchers, clinicians, and patients be wary of results from studies with this potential bias until researchers can either eliminate the bias or show that their results are not affected by it.
African American women are much more likely to be diagnosed with aggressive breast cancer tumors than are white women, according to a study in the August 9 online issue of Cancer from researchers at Yale University School of Medicine, led by Dr. Beth Jones. The study found that there were racial differences in genetic alterations, with African American women having a greater chance of carrying changes in the p53 tumor suppressor gene. The study was funded by NCI and the U.S. Department of Defense.
While white women have the highest rate of breast cancer, African American women have the highest death rate of all races from the disease. This anomaly persists even when adjusting for age, socio- economic status, and disease stage.
The researchers compared tumor samples from 145 African American women and 177 white women. They found that African American women were significantly more likely to have later stage tumors, larger tumors, positive lymph nodes, and tumors with higher histologic and nuclear grades - all characteristics associated with a poor outcome. "This study offers new evidence for possible racial/ethnic differences with regard to p53 alterations," wrote Dr. Jones.
In an accompanying editorial, Dr. Lisa Newman of the Breast Care Center at the University of Michigan noted that ethnic background differences in breast cancer incidence and mortality are observed worldwide. "The excellent study by Dr. Jones provides an example of how advances in medical technology are allowing the oncology community to explore population-based variation in breast carcinoma epidemiology on a more scientific level," she wrote.
Androgen suppression therapy (AST) combined with standard radiation therapy (RT) increases survival in men with localized prostate cancer when compared to RT alone, according to study results reported in the August 18 Journal of the American Medical Association. The prospective study was conducted by Dr. Anthony D'Amicio and colleagues at Brigham and Women's Hospital and the Dana Farber Cancer Institute in Boston.
Previous studies have shown the benefits of a 3-year course of combination treatment in men with locally advanced and high-risk prostate cancer. But, AST for more than 1 year is associated with negative side effects, including decreased bone mass; impairment of memory, attention, and executive functions; anemia; muscle loss in exchange for body fat; hot flashes; and impotence.
To determine the efficacy of a shorter combination therapy regimen, Dr. D'Amicio and colleagues recruited 206 participants with clinically localized prostate cancer to this trial, randomizing them to receive either 70 Gy RT alone or the same dose of RT combined with 6 months of AST. After an average follow-up of 4.5 years, results projected that the 5-year survival rate for patients in the combination-therapy arm would be 88 percent, compared to 78 percent for patients in the RT arm. The authors noted that "decreasing AST duration could profoundly impact a patient's quality of life," and suggested additional avenues of research, such as the survival benefits of additional radiation sites and higher radiation dosage in combination therapy.
Cancer survivors are more likely to report poorer health than similar individuals without cancer, according to a study published in the September 1 Journal of the National Cancer Institute. Cancer survivors reported significantly poorer outcomes in both quality of life and work productivity. This finding was consistent across multiple tumor types and times since diagnosis.
"What are the non-medical costs of cancer?" asks lead author Dr. Robin Yabroff of NCI's Division of Cancer Control and Population Sciences. To examine this burden of cancer, Dr. Yabroff and colleagues analyzed data from the 2000 National Health Interview Survey. A total of 1,823 cancer survivors and 5,469 age-, sex-, and educational attainment-matched control subjects were included in the study.
While prior cancer burden studies have focused mainly on the costs of treatment, this study focused on two other elements: productivity loss and quality of life. Even long-term survivors with 11 or more years since diagnosis were more likely to report more lost productivity and worse quality of life than similar individuals without cancer. "The findings are pretty compelling, and cancer burden appears to go beyond the costs of medical care," says Dr. Yabroff. This study is one component of NCI's Health Services and Economics Branch's efforts to disseminate data resources to support policy-relevant research on economic and health services research questions and improve measurement of cancer burden.
NCI scientists have identified associations between expression of individual transporters in cancer cells and the development of resistance, and sensitivity, to specific drugs. The research, published in the August 22 issue of Cancer Cell, details the gene expression of a 48-member family of membrane proteins called ABC transporters, for which the multidrug resistance gene MDR1 is the prototype.
ABC transporters regulate the traffic of molecules - including hormones and lipids - in and out of cells. Many of these 48 proteins transport toxic materials out of cells, conferring drug resistance. "Multidrug resistance is a major barrier to effective cancer chemotherapy," said Dr. Gergely Szakács, one of the study authors, adding "even low levels of resistance can have a significant impact on the efficacy of chemotherapy."
The study team, which also included Drs. Jean-Philippe Annereau, Michael Gottesman, and collaborators in the laboratory of Dr. John Weinstein, discovered 131 strongly correlated drug-gene pairs where the expression of a specific ABC transporter was accompanied by decreased sensitivity to particular drugs. Conversely, the expression of some ABC transporters, most notably MDR1, caused an increase in cancer cells' sensitivity to some drugs. This increase was unexpected, as MDR1 is perhaps the best-known multidrug resistance protein. Identification of drugs with increased activity in MDR1 expressing tumor cells raises the exciting possibility of eventually using such compounds against cancers expressing MDR1. The researchers advocate further investigation in order to discover more compounds that may interact in this way with MDR1 and other ABC transporters.
The research team has catalogued information about these drug-gene pairs in a database, which is available at http://discover.nci.nih.gov/ABC. The authors expect the database to spur further research into novel therapies designed to either evade or exploit the identified drug-gene associations.