Daily use of at least one aspirin may reduce the risk of prostate cancer by 15 percent, according to the results of a prospective study released at the American Association for Cancer Research (AACR) annual meeting this week in Orlando, Fla. The results are consistent with findings from a recent meta-analysis of observational studies on aspirin use and prostate cancer, said the study's lead author, Lori Sakoda, an epidemiologist in NCI's Division of Cancer Epidemiology and Genetics.
In the study, Ms. Sakoda and colleagues examined the relationship between use of the nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin and ibuprofen and prostate cancer risk in more than 29,000 men enrolled in the screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. The PLCO trial - a massive clinical trial with more than 154,000 participants - was launched in 1992 to determine whether certain screening tests can reduce deaths from these four cancers. In addition, PLCO substudies are assessing additional epidemiologic factors that affect the risk of these and other cancers.
This investigation involved men in the trial who had undergone a digital rectal examination and prostate-specific antigen testing between November 1993 and September 2001. At entry into the trial, all men completed a self-administered questionnaire on NSAID use in the previous 12 months; they were then followed for the remainder of the study period. Overall, approximately 31 percent of participants reported daily aspirin use, while only 7.5 percent reported daily ibuprofen use.
In the study cohort, there were 1,338 cases of prostate cancer. Compared with men who took 0 to 3 aspirins per month, the relative risk of prostate cancer was reduced by 14 percent in men who reported taking a single aspirin daily and 21 percent in men who took two or more daily.
Despite the study's findings, "There are not sufficient data to recommend daily use of aspirin solely to prevent prostate cancer," Ms. Sakoda said. "We still lack data on important considerations, such as the optimal dose, duration, and timing of aspirin use."
Men with higher levels of vitamin E in their blood were found to have a lower risk of developing prostate cancer, according to Drs. Stephanie J. Weinstein and Demetrius Albanes, researchers from NCI's Division of Cancer Epidemiology and Genetics, who reported their study results at the annual meeting of the American Association for Cancer Research in Orlando, Fla.
The study involved 300 men between the ages of 50 and 69 who were part of a larger prevention trial examining the effect of beta-carotene and vitamin E on lung and other cancer risk. During recruitment for the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) trial, which took place between 1985 and 1988, serum samples from each of nearly 30,000 Finnish participants, all of whom were smokers, were frozen and stored.
For the current report, the investigators defrosted serum samples from 100 men who developed prostate cancer over the course of the original trial. They then defrosted serum samples from 200 matched control men who did not develop prostate cancer. The scientists measured the two principal forms of vitamin E in the blood, alpha-tocopherol and gamma- tocopherol. Men with the highest serum levels of alpha-tocopherol had a 53 percent reduction in risk and those with the highest levels of gamma-tocopherol had a 39 percent lower risk.
The impetus for the current study grew out of an unexpected finding from the larger trial, in which men who took vitamin E supplements had a 32 percent lower incidence of prostate cancer (JNCI, 1998; 90:440). The investigators wanted to see if the amount of vitamin E in the serum before the men were given vitamin E pills was also related to their chance of getting prostate cancer.
This finding needs to be verified in other studies, Dr. Weinstein said, including other ethnic groups and nonsmokers. The SELECT prevention trial, which is expected to end in 2013, is investigating the effect of selenium and vitamin E supplements on prostate cancer risk and includes minorities and nonsmokers.
Pregnancies that end in miscarriages or abortions do not increase a woman's risk of developing breast cancer, according to a study published in the March 27 issue of The Lancet. The study, conducted by members of the Collaborative Group on Hormonal Factors in Breast Cancer, analyzed data from 53 prospective and retrospective epidemiological studies performed in 16 countries.
Researchers analyzed prospective data from 44,000 women with breast cancer. This group of women had participated in studies where they reported their history of abortion or miscarriage before they were diagnosed with breast cancer.
Results were expressed as the "relative risk" of breast cancer, which compares the chances of developing breast cancer in women with, and without, some such record of abortion. A relative risk of 1.0 or less indicates no adverse effect on the subsequent risk of breast cancer. In the prospective studies, the average relative risk of breast cancer was 0.98 for women who had a pregnancy that ended as a miscarriage and 0.93 for women who had a pregnancy that ended as an abortion, indicating no increased risk of breast cancer after miscarriage or abortion.
The retrospective data included information from 39,000 women who were asked about their history of abortions or miscarriages after they were diagnosed with breast cancer. Researchers noted that these studies are potentially less reliable than the prospective studies and can give misleading results. In interviews, Dr. Richard Peto, one of the study authors, said, "Studies can give misleading results if women are asked about previous abortions only after they are diagnosed with breast cancer. This may well be because, on average, women with breast cancer are more likely than other women to disclose any prior induced abortions."
"The totality of the worldwide epidemiological evidence indicates that pregnancies ended by induced abortion do not have adverse effects on women's subsequent risk of developing breast cancer," commented Dr. Valerie Beral, another of the study authors.
Editor's Note: These results add further weight to the conclusions from NCI's Early Reproductive Events and Breast Cancer Workshop in February 2003. Workshop participants concluded that having an abortion or miscarriage does not increase a woman's subsequent risk of developing breast cancer. A summary of their findings, titled Summary Report: Early Reproductive Events and Breast Cancer Workshop, can be found at http://cancer.gov/cancertopics/ere-workshop-report.
The GOELAMS research group has completed a clinical trial demonstrating that a high-dose multidrug chemotherapeutic regimen, when combined with autologous stem-cell support, may prove superior to standard chemotherapy in some adults newly diagnosed with aggressive non-Hodgkin's lymphoma (NHL). A four-drug regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has long been considered the standard of care for these patients. But several recent clinical trials have shown that a high-dose multidrug regimen known as CEER, which is similar but not identical to CHOP, can have promising results in patients with aggressive lymphoma when followed by autologous stem cell transplantation.
This randomized, controlled clinical trial, described in the March 25th issue of the New England Journal of Medicine, is the first to directly compare this newer form of multimodality therapy with CHOP in adult NHL patients with aggressive, disseminated disease. Patients were randomly assigned to two arms, with one receiving CHOP and the second CEER, followed by stem cell transplantation. Each arm was stratified into three subgroups according to whether patients had a low, low-intermediate, or high-intermediate risk of death. The event-free survival rate at five years was found to be significantly higher in the multimodality groups than in the CHOP groups: 55 percent compared with 37 percent, respectively. Among patients with a high-intermediate risk of death, the improvement in event-free five-year survival rates was more striking: 74 percent versus 44 percent, respectively. No improvement in overall survival rates after five years, however, was observed after CEER/transplant treatment. Further, no significant differences in either event-free or overall five-year survival were observed in any patients with a low or low-intermediate risk of death.
This study adds to the growing body of evidence supporting the principle that to be optimally effective, the choice among treatment options should be individually tailored to patients' precise prognostic profiles. The authors urge caution in assessing the significance of this study and discuss several of the study's limitations.
In an accompanying editorial, Dr. T. Andrew Lister concurs with the authors' assessment of the study's limitations. Nonetheless, he acknowledges that the study's findings "constitute a modest advance," concluding that "[i]t is incumbent on us to build on this information . . . so that we can continue to make incremental improvements in care."
Speaking at a special forum on cancer vaccines at the annual AACR meeting, Dr. Jeffrey Schlom, chief of NCI's Laboratory of Tumor Immunology and Biology (LTIB), discussed preclinical and clinical results from his laboratory's work using cancer vaccines in conjunction with conventional cancer therapies.
Cancer vaccine targets are typically overexpressed in tumors as opposed to normal tissue, which greatly reduces the risk of autoimmunity - the chance of the body mounting an immune response against normal tissue. The targets, called tumor associated antigens, only trigger a weak immune response or none at all, unless strategies are undertaken to make them more immunogenic. One of the main targets that Dr. Schlom's laboratory has identified is the carcinoembryonic antigen (CEA), which is normally only expressed in the fetal gut and is present in very low levels in the normal adult colon. "CEA is a particularly attractive target," commented Dr. Schlom, "because it is overexpressed in the vast majority of a wide-range of carcinomas including colorectal, pancreatic, and breast."
Dr. Schlom also discussed his work to increase the natural amount of T-cell activation by the cancer vaccines, thereby making them much more effective tumor killers. His group has been looking into varying the type of viral vector used and the fashion in which the vectors are administered. Previously, they identified that the greatest efficacy results from a protocol that involves an initial vaccination using a vaccinia vector followed by subsequent vaccinations using an avipox vector.