News Release

Other highlights in the March 7 JNCI

Peer-Reviewed Publication

Journal of the National Cancer Institute

Changes in Breast Density May Impact Breast Cancer Risk

Changes in breast density within a three year period may impact breast cancer risk, according to a new study. The two measurements of breast density needed to calculate that change may better predict a woman's risk of breast cancer than a single measurement.

High breast density is a strong predictor of breast cancer risk, but researchers did not know whether changes in breast density over time would affect this risk. Karla Kerlikowske, M.D., of the University of California, San Francisco, and colleagues looked at breast density data from 301,955 women aged 30 and older who had received at least two mammograms between January 1993 and December 2003. Of those women, 2,639 were diagnosed with breast cancer within 12 months of their last screening.

An increase in breast density was associated with a greater risk of breast cancer, regardless of the woman's original breast density measurement. Women with lower breast density after their second mammogram had a reduced risk of breast cancer, except for those who were initially in the highest density group.

"It is not known why some women may have an increase in breast density over time with increasing age," the authors write. "Decreasing weight, increased alcohol intake, or changes in diet or medication may contribute to increasing breast density, and their possible effects on changes in breast density over time warrant further study."

Contact: Steve Tokar, Communications Manager, Northern California Institute for Research and Education, steve.tokar@ncire.org, (415) 221-4810 x5202


Targeting Prostate-Specific Proteins May Lead to New Treatments for Prostate Diseases

By targeting a protein unique to the prostate gland, researchers may have found a compound that is a safe and effective treatment for prostate cancer and other prostate diseases.

As they age, most men will develop some sort of prostate abnormality, such as enlargement of the prostate or prostate cancer. A drug that is activated by prostate-specific antigen (PSA) "a protein produced by both the normal and diseased prostate gland"could be effective in treating prostate diseases while leaving non-prostate cells unharmed.

Simon Williams, Ph.D., of The Johns Hopkins Oncology Center in Baltimore, and colleagues synthesized a PSA-activated protoxin, called PRX302, and tested it in prostate cancer cells and several animal models. PRX302 caused prostate cancer tumors to shrink when injected directly into mice tumors. Because PRX302 is activated only in the presence of PSA, cells that do not express PSA were unaffected. A phase I clinical trial has already begun to test the toxicity of PRX302.

"The development of novel therapies to treat prostate cancer could be of substantial benefit to large numbers of men," the authors write. "Current therapies for these local recurrences include techniques that are associated with substantial morbidity, including increased rates of incontinence and impotence."

Contact: Samuel Denmeade, Johns Hopkins University School of Medicine, denmesa@jhmi.edu, (410) 502-3941


EXT1 Gene Influences Formation of Nonhereditary Benign Bone Tumors

Mutations in a gene known as EXT1 cause Multiple Osteochondromas, a rare hereditary disorder that results in the formation of benign cartilage-covered bone tumors. Now scientists have shown that EXT1 is also involved in the development of nonhereditary osteochondromas, the more common form of the disease.

Liesbeth Hameetman of Leiden University Medical Center in The Netherlands, and colleagues examined eight nonhereditary osteochondromas to determine whether EXT1 acts as a tumor-suppressing gene in nonhereditary osteochondromas in the same way it does in hereditary ones. Mutations or deletions of tumor suppressor genes increased the likelihood of a cell becoming a tumor cell, but both copies of the gene had to be affected for this to happen.

In seven of the eight osteochondromas, both copies of EXT1 were deleted; these deletions occurred only in the cartilage cap of the one osteochondroma that was examined in detail. Previous studies demonstrated that the cartilage cap was formed of tumor tissue, but it was unknown whether other parts of the osteochondromas the bony stalk and the connective tissue were as well. The authors conclude that EXT1 acts as a tumor suppressor gene in the cartilage of nonhereditary osteochondromas.

"Our finding that the cartilage cap is the only [tumor] component of osteochondroma revives long-standing debate about the cell origin of osteochondromas," the authors write.

Contact: Pancras Hogendoorn, Leiden University Medical Center, p.c.w.hogendoorn@lumc.nl


Breast Cancer Prevention Drugs Show Additional Health Benefits

The results from the Study of Tamoxifen and Raloxifene (STAR) trial, one of the largest breast cancer prevention clinical trials ever conducted, provide a good opportunity to look back at the obstacles and successes in the development of these two drugs, according to a commentary by V. Craig Jordan, Ph.D., D.Sc., of Fox Chase Cancer Center in Philadelphia. He discusses the discovery and development of these two drugs, their benefits outside breast cancer prevention, such as treating osteoporosis, and a glimpse into future research.

Both tamoxifen and raloxifene belong to a class of drugs known as selective estrogen receptor modulators (SERMs), which have been shown in clinical trials to successfully prevent breast cancer. These drugs act by occupying estrogen receptors in breast and other tissue, and therefore block estrogen's message to the cell to divide and spread.

While the STAR trial demonstrated that development of new chemoprevention drugs is a slow, often unpredictable, process, chemoprevention must remain a priority, Jordan says. Both tamoxifen and raloxifene have been highly effective at reducing the incidence of breast cancer and in the case of tamoxifen, the death rates when used to treat breast cancer. Nevertheless, it's important that research continue in order to develop new prevention options, specifically cost-effective treatments that are intended for premenopausal women.

"For the moment, raloxifene is proving to be an important advance in chemoprevention because it is a multifunctional medicine that can target women at low risk for breast cancer with [low bone mineral density] and healthy women with a high risk of breast cancer. Nevertheless, new SERMs are necessary for clinical testing in postmenopausal women. The SERM concept clearly works, but a long-acting SERM is required to replace raloxifene, a drug that does not appear to perform optimally in a high-estrogen environment," Jordan writes.

Contact: Karen Mallet, Public Relations Director, Fox Chase Cancer Center, karen.mallet@fccc.edu, (215) 728-2700

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Also in the March 7 JNCI:

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.


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