Cancer Research Highlights
Breast Cancer Risk in Survivors of Childhood Cancer Quantified
In the largest study of its kind, researchers led by Dr. Peter Inskip of NCI's Division of Cancer Epidemiology and Genetics estimated the relationship between exposure to radiation during childhood cancer treatment and adult breast cancer risk in 6,647 women from the Childhood Cancer Survivor Study (CCSS). The results were published July 20 in the Journal of Clinical Oncology.
Overall, women who received any radiation therapy for their initial cancer were 2.7 times as likely to develop breast cancer. The risk increased linearly with increasing radiation dose to the area where the tumor developed in the breast, reaching 11-fold for doses in the highest category of exposure (40 Gray), relative to no radiation.
The women had been diagnosed with their primary cancer as children, between 1970 and 1986. One hundred twenty developed breast cancer by the end of 2001 and gave consent to have their medical records reviewed. The researchers matched each of the 120 women with 4 women in a control group from the CCSS who had not developed breast cancer. Medical physicists estimated radiation doses to the breast and ovaries.
Interestingly, women who had received radiation to the breast as well as a sterilizing radiation dose to the ovaries (which stops ovarian hormone production) had a sharply reduced risk of radiation-related breast cancer. "A radiation dose to the breast can cause damage that may potentially develop into cancer, but whether that damage does develop into cancer can be influenced by hormonal stimulation from the ovaries," explained Dr. Inskip.
The authors noted that modern radiation therapy for most types of childhood cancer uses substantially lower radiation doses than protocols used between 1970 and 1986. In addition, said Dr. Inskip, "we're highlighting the complications of treatment here, but we should remember that there has been remarkable progress in treating childhood cancer. Many children who might have died from their cancer are living due to advances in treatments."
Thalidomide Does Not Help in Small Cell Lung Cancer
Adding the drug thalidomide to chemotherapy did not help patients with small cell lung cancer (SCLC) live longer, but it did increase the risk of developing blood clots in veins deep within the body, British researchers reported in the Journal of the National Cancer Institute on July 16. Thalidomide was evaluated in this disease because of its ability to inhibit angiogenesis, or the growth of blood vessels, in tumors. Angiogenesis is thought to play an important role in SCLC, which accounts for about 20 percent of lung cancers.
The drug has improved survival for people with other cancers, but it provided no benefit in the first phase III, randomized trial of an antiangiogenic agent in SCLC. In the 724-person study, Dr. Siow Ming Lee of University College Hospital in London and his colleagues found that survival was essentially the same (about 10 months) in both the thalidomide group and the chemotherapy-alone group. Patients in the thalidomide group, however, faced a higher risk of clotting events such as deep vein thrombosis and pulmonary embolus.
In addition, patients with extensive disease in the thalidomide group fared worse than those in the chemotherapy-alone group. Targeting angiogenesis may not work as well in SCLC as in multiple myeloma and colorectal cancer, perhaps because of differences in the angiogenic pathways involved, the researchers concluded.
The notion that thalidomide has antiangiogenic effects in patients should be revisited, noted an accompanying editorial. But the biology of SCLC is still poorly understood, and the authors suggested that it may make sense to focus now on laboratory research that could lead to new insights and identify promising therapeutic targets.
New Role Found for Tumor-suppressor Protein
Japanese researchers have identified a previously unknown function for the protein p53, which helps the body suppress tumors. A team from the University of Tokyo found that p53 also plays a role in the processing of microRNAs, snippets of genetic material that regulate genes. The loss of p53 may affect the processing of several microRNAs with anticancer properties, the team reported in the July 23 Nature.
The gene for p53 is mutated in half of all cancers, and in a majority of tumors the p53 pathway is inactivated. The protein is thought to protect against cancer in cells with DNA damage by activating genes that cause the cells to either commit suicide or stop growing rather than progress to a tumor. Together with previous research, the new results suggest that p53 mutations can disrupt several tumor-suppressive functions at once, including the induction of cell suicide and the processing of microRNAs that help suppress abnormal cell growth.
These results may have implications beyond the cell's response to DNA damage and cancer, according to an accompanying editorial, because mutations in p53 could alter other aspects of RNA metabolism besides microRNA processing. Future studies will need to determine precisely which microRNAs are regulated by p53 and describe the underlying mechanisms involved.
Some researchers have been exploring ways to re-activate p53 in cells where the protein has been disabled, but this has so far proved to be a challenge. The current study suggests that doing so would restore anticancer functions that were previously unappreciated.
Clinical Trial Caution: Meeting Abstract May Differ from Final Publication
Randomized clinical trials of cancer therapies are often reported as preliminary results in the form of abstracts at major scientific meetings. But, as a new study documents, the conclusions of these abstracts may not agree with the subsequent final analyses published by the trial investigators in peer-reviewed journals. In about 10 percent of the trials analyzed, there was a reversal in the researchers' conclusions about the efficacy of treatment when the abstracts were compared with the final report.
Given the potential for non-final results to mislead and even affect how the trial continues, clinicians, investigators, and the organizers of conferences should be cautious when interpreting results from randomized clinical trials, Canadian researchers from the NCIC Clinical Trials Group reported online last week in the Journal of Clinical Oncology.
The researchers assessed 138 randomized clinical trials, published between 2000 and 2004, in four major cancers (lymphoma, breast, colorectal, and non-small cell lung cancer). For each trial, the researchers identified and analyzed corresponding abstracts that had been presented at seven major cancer meetings between 1990 and 2004. All of the abstracts presented efficacy results.
"A substantial percentage of trials will see an important change in their conclusions from the time of abstract presentation to the final publication," said lead investigator Dr. Christopher Booth of Queen's University Cancer Research Institute. "This means that clinicians need to be cautious before changing their practice based on preliminary results of randomized trials."
Just as important, the authors of abstracts have a responsibility to clearly identify non-final results, commented Dr. Benjamin Djulbegovic of the University of South Florida and H. Lee Moffitt Cancer Center & Research Institute, who studies clinical trials. "The bottom line is that people who use the information in these abstracts need to know when results are preliminary."