NCI Cancer Bulletin: A Trusted Source for Cancer Research NewsNCI Cancer Bulletin: A Trusted Source for Cancer Research News
January 18, 2005 • Volume 2 / Number 3 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Cancer Research HighlightsCancer Research Highlights

FDA Approves Abraxane for Breast Cancer

On January 7 the US Food and Drug Administration (FDA) approved Abraxane for treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.

Abraxane is the first in a new class of "protein-bound particle" drugs and consists only of albumin-bound paclitaxel nanoparticles. This new formulation of paclitaxel does not have to be dissolved in a toxic solvent or require steroids or special equipment for administration. The solvent needed to dissolve the original paclitaxel often causes severe allergic side effects requiring treatment with steroids, which can cause additional side effects.

Androgen Deprivation Therapy Increases Fracture Risk

Elderly prostate cancer patients taking androgen deprivation therapy have a greater risk of bone fractures compared with prostate cancer patients who don't use the increasingly popular treatment, according to a study published in the January 13 New England Journal of Medicine.

The potential for fracture risk from androgen deprivation therapy - whether through use of gonadotropin-releasing hormone (GnRH) agonists or orchiectomy - has long been suspected. However, "our study is the first to provide an estimate of the risk of fracture attributable to androgen deprivation therapy by including prostate cancer patients not treated with androgen deprivation, and adjusting for known confounding variables," noted Dr. Vahakn B. Shahinian and colleagues from the University of Texas Medical Branch at Galveston.

The study is based on data from NCI's Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. It used a sample of 51,218 prostate cancer patients aged 65 and older who were first diagnosed between 1993 and 1997. After a follow-up period of 60 months, the researchers found that 19.4 percent of the androgen deprivation group had a fracture, versus 12.6 percent in the control group.

Authors cautioned that the "relatively modest hazard ratios found in our study could have a major adverse impact." The researchers estimated "there would be approximately 2,800 excess fractures per year attributable to GnRH agonist therapy." They noted a dramatic rise in use of GnRH agonists for treatment of early stages of the disease although "there has been no evidence from clinical trials of survival benefit."

Deficient DNA Repair Capacity Increases Breast Cancer Risk

By comparing female breast cancer patients with their healthy biological sisters, researchers at Columbia University found that the body's deficient ability to repair DNA damage may be "a valuable in vitro biomarker to identify high-risk subjects, especially in familial breast cancer families."

The study, in the January 19 issue of the Journal of the National Cancer Institute, compared blood tissue samples from sisters who participated in the Metropolitan New York Registry of Breast Cancer Families. This is one of six major sites funded by NCI as part of the Breast Cancer Family Registry.

Researchers exposed the sisters' lymphoblastoid cells in vitro to the chemical carcinogen benzo[a]pyrene diolepoxide (BPDE), which is known to cause DNA damage. They initially found that the number of BPDE-DNA adducts - bonds between the chemical and DNA - created were comparable between and across all subject groups. However, after allowing 4 hours for DNA repair to occur, they found that significantly more of the adducts had been removed in the healthy sisters' cells than in the cells of the breast cancer patients.

The cancer patients' cells were 8.6 percent less effective than their sisters' cells in responding to the mutagenic assault. Also, women who had the lowest levels of DNA repair capability had double the risk for breast cancer compared with women who had the highest capability. The largest differences were found between patients and controls younger than age 40. The relative risk of breast cancer was nearly 3 times greater between the groups with the most and the least DNA repair capabilities.

Findings from the new study echo results from previous studies on DNA repair capacity for lung cancer patients and their family members.

Diabetes and Cancer Risk Link Not Tied to Obesity

A prospective cohort study of almost 1.3 million Korean men and women confirmed previous research showing a link between increased levels of fasting serum glucose and an increased risk of various types of cancer. The NCI-funded study, published in the January 11 Journal of the American Medical Association, noted the additional finding that the risk wasn't related to the subjects' body weights because the Korean study population was "far leaner than the Western populations in other studies."

Overall, only about one-fourth of the men and women in the Korean Cancer Prevention Study (KCPS) had body mass index rankings greater than 25. As a consequence, the researchers explained, the study's findings "do not reflect confounding by obesity, suggesting that the mechanism of cancer risk reflects the consequences of hyperinsulinemia."

KCPS assessed the association between high levels of fasting serum glucose, or diabetes, with cancer risk. During the 10 years of follow-up since 1993, researchers found "linear trends in mortality with increasing serum glucose levels for all cancers combined and for cancers of several sites."

The strongest link was found with pancreatic cancer - an estimated two-fold increase in risk compared with nondiabetic men. KCPS also found significant associations with increased risk in men for cancers of the esophagus, liver, and colorectal system and increased risks for liver and cervix cancers in women.

The researchers reported that being overweight does increase the likelihood of developing glucose intolerance and that "may be one pathway by which obesity increases cancer risk."

Study Demonstrates Gene Expression Microarrays are Comparable and Reproducible

An NCI-funded study shows for the first time that independently prepared gene expression microarrays can produce highly comparable results. Four separate laboratories prepared microarrays on portions of the same set of samples; their comparisons, appearing in the January 15 Clinical Cancer Research, showed that overall correlation of similar samples was extremely high, and expression correlation between separate labs was only slightly lower than correlation within the same labs.

The potential clinical use of microarrays may require large-scale studies and necessitate that data be produced in different laboratories and subsequently combined for analysis. However, even if all procedures and equipment were standardized, small differences between labs could produce different profiles.

Twelve different tumor tissues, five cancer cell lines, and five purified RNA samples were blinded and randomized to one of four testing laboratories that followed a common protocol for all steps of sample preparation and microarray analysis. All within-lab profiles were highly reproducible and, while between-lab correlation values decreased slightly, expression profiles of all similar samples could be accurately grouped together. The researchers also found that laboratory practices comprised the smallest source of variation in the expression profiles; biological differences in the tissue samples were the largest source of variation.

"This evaluation is a key step in moving gene expression data from small-scale bench science into large-scale clinical practice," said Dr. James Jacobson, chief of NCI's Diagnostic Biomarkers and Technology Branch.