Some 23 percent of the participants aged 55 to 74 in NCI's Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial have at least one polyp or mass in their lower colons, according to results from the largest study to date of flexible sigmoidoscopy. The study, published in the July 6 Journal of the National Cancer Institute, also found that 83 percent of participants who were offered sigmoidoscopy agreed to the procedure, which the authors characterize as a high rate of acceptance.
Starting in 1993, some 155,000 people enrolled in the PLCO Trial, which is being conducted at 10 centers nationwide. Half of the participants were offered screening sigmoidoscopy, and the other half maintained usual care with their own physicians. After the screening, patients with polyps or masses were referred to their primary physicians for follow-up. Twenty-eight percent of men were referred for follow-up visits, compared with 18 percent of women.
One year after the initial screening, 1.8 per 1,000 women and 2.9 per 1,000 men had been diagnosed with colorectal cancer, usually after colonoscopy and biopsy.
Women turned down sigmoidoscopy more often than men, with women older than 70 having the highest rejection rate.
Dr. Paul Pinsky, of NCI's Division of Cancer Prevention, said that the figures establish a benchmark for what could be expected if a large-scale flexible sigmoidoscopy screening program was undertaken in the United States. He said the study's large population and broad geographic catchment area, as well as the fact that diagnostic follow-up was carried out by independent health care providers not associated with the trial, make it more representative of actual practice than most other screening trials. However, he noted that the study population was somewhat less diverse and more educated than the U.S. population as a whole.
The PLCO Trial will eventually show whether screening reduces the death rate from the four cancers being studied.
Taking low doses of aspirin every other day for 10 years did not protect women against cancer, the largest clinical trial of aspirin in cancer prevention has found. The dose was 100 mg every other day. Higher doses of aspirin may have protective effects, the researchers say, but increasing the dose could potentially lead to side effects in some individuals.
"The results at this time do not support the use of low-dose aspirin for cancer prevention," says Dr. Nancy Cook of the Brigham and Women's Hospital in Boston, lead author of the study published online in the July 6 Journal of the American Medical Association (JAMA).
The findings are from the Women's Health Study, a randomized trial that evaluated the protective effects of aspirin and vitamin E on cancer and cardiovascular disease among 40,000 women aged 45 and over. Participants were free of cancer and cardiovascular disease at the start of the study.
No benefit was detected for the cancers examined, including breast and colon, but the researchers cannot rule out the possibility that aspirin may protect against lung cancer. Two studies in men have reported similar findings, but "the evidence for such an effect remains uncertain," the researchers write.
A companion report in JAMA from the Women's Health Study found no evidence that taking 600 IU of vitamin E every other day for 10 years protects women against cancer. "The best recommendation for the prevention of cancer and cardiovascular disease is to follow a healthy lifestyle," notes Dr. Cook.
A new study reports that certain variants of a gene involved in regulating pigmentation are associated with an increased risk of melanoma in an Italian population, as they are among lighter-skinned populations in Northern Europe. The variants were strongly associated with melanoma risk in both the familial and noninherited, or sporadic, forms of the disease in the Italian population.
The melanocortin-1 receptor (MC1R) gene, also known as the "freckling" gene, comes in dozens of forms. Some variants, like those typically found in people with red hair, have been linked to the risk of melanoma, but this was the first study to test associations between the variants and melanoma in a Mediterranean population.
After the researchers took into account known risk factors, such as hair color, tanning ability, and the presence of moles, some unexplained risk remained. In fact, the risk of melanoma tended to be higher among individuals with fewer known risk factors, according to findings in the July 6 Journal of the National Cancer Institute.
"MC1R is a very interesting gene," says Dr. Maria Teresa Landi, of NCI's Division of Cancer Epidemiology and Genetics, who led the research. "We believe it is important for pigmentation, but its effects on the risk of melanoma extend beyond pigmentation. We and others are trying to understand these effects."
The MC1R variants were also associated with the thickness of melanoma, which is an indicator of disease progression. In contrast, the researchers found no association in this population between melanoma risk and a variant of the Agouti Signaling Protein gene, which is also involved in pigmentation. The study included 276 melanoma patients and 382 people without the disease in northeastern Italy.
During the second and third trimesters of pregnancy, chemotherapy can be given to women who have breast cancer with minimal risk of peripartum complications or serious adverse effects on the fetus. These are the results of a retrospective study published in the June 20 Journal of Clinical Oncology.
The study included 28 women who had been treated for breast cancer with chemotherapy during pregnancy at any of five London hospitals between 1986 and 2003. Sixteen of the women received anthracycline-based chemotherapy during treatment, while the remaining 12 received cyclophosphamide, methotrexate, and fluorouracil.
One woman who was treated during the first trimester of her pregnancy miscarried. Among the remaining women, 22 were in their second trimester and 5 were in their third trimester. Analysis showed a median gestational age at delivery of 37 weeks; the infants were within normal birthweights and had no significant fetal abnormalities.
Based on similar studies - one of which included long-term follow-up data showing no malignancies in the children of women who underwent chemotherapy during pregnancy - the authors suggest that chemotherapy during the second and third trimesters of pregnancy could also be safe for babies in the long term. But they note that large prospective studies are needed to confirm this trend. "Nonetheless," they write, "on the basis of the current evidence, women should not be denied the potential benefits of chemotherapy because they are pregnant at the time of diagnosis of breast cancer."
The standard adjuvant treatment for metastatic colon cancer is a combination of the drugs fluorouracil plus leucovorin. But depending on how the drugs are administered, side effects can include diarrhea, a weakened immune system, and inflammation of the mucous tissue in the mouth. To see whether capecitabine (Xeloda), an established first-line treatment for metastatic disease, could be used as an alternative adjuvant treatment with fewer negative side effects, an international coalition of researchers recruited 1,987 patients with resected stage III colon cancer to the X-ACT clinical trial. Their results are published in the June 30 New England Journal of Medicine.
After 24 weeks of treatment and a median follow-up period of 3.8 years, patients in the capecitabine group showed disease-free survival that was at least equivalent to those in the fluorouracil-plus-leucovorin group. They also showed longer relapse-free survival, with 65.5 percent of the patients remaining relapse free after 3 years, compared with 61.9 percent of those in the fluorouracil-plus-leucovorin group.
In addition, patients in the capecitabine group had fewer treatment-related side effects, including nausea, diarrhea, vomiting, hair loss, and a weakened immune system. There was one exception: incidence of grade 3 hand-and-foot syndrome - a condition where the skin on patients' palms and soles of their feet becomes red and tender, and may peel - was significantly higher in the capecitabine group.
"Our results support capecitabine as an alternative to fluorouracil plus leucovorin in the adjuvant treatment of colon cancer," the authors write. "Capecitabine or oxaliplatin-based therapy should be considered for all patients requiring adjuvant therapy for colon cancer."
A relatively rare and aggressive form of breast cancer called inflammatory breast cancer (IBC) may be slightly more common among women in the United States today than it was 15 years ago, according to an analysis of more than 180,000 breast cancer cases diagnosed between 1988 and 2000. This form of breast cancer is characterized by redness, warmth, and swelling, often without an underlying palpable mass.
The incidence of IBC increased from 2 cases per 100,000 to 2.5 cases per 100,000 between 1988 and 1999, according to findings in the July 6 Journal of the National Cancer Institute. (By comparison, during the same period, the incidence of more common forms of breast cancer decreased from 108 cases per 100,000 to 101 cases per 100,000.)
The reasons for the apparent increase are unclear, but it will be important to determine whether the incidence is actually rising, or whether IBC is simply better recognized today than in the past, comments Dr. Paul Levine, of the George Washington University Cancer Institute, who led the study with Dr. Kenneth Hance of NCI's Division of Cancer Prevention.
The true incidence of IBC has long been unclear. In this study, the researchers developed a "case definition" of the distinct clinical and pathological characteristics of IBC. They then surveyed the Surveillance, Epidemiology, and End Results (SEER) Program database and determined that 2 percent of breast cancer cases appeared to be IBC. Despite modest improvements in IBC survival throughout the 1990s, the authors observed significant racial disparities in which the incidence was higher and survival was worse among African American compared with Caucasian IBC patients.
Improved methods of recognizing IBC will help researchers classify patients, identify subtypes of disease, and discover molecular "signatures" for diagnostic and prognostic purposes. "Getting a molecular handle on the tumor is very important," notes Dr. Levine, who has developed an IBC registry and tissue repository.