printable versionQuick study: One on breast cancer and MRIs, another on cholesterol and tumors
THE QUESTION: Is MRI screening, which is much more expensive than mammography, warranted for women at great risk of developing breast cancer?
THE BACKGROUND: Screening with magnetic resonance imaging can detect breast cancer earlier than mammography in some women who are at high risk of contracting the disease. Although breast MRI screening is highly sensitive, it increases the rate of false-positive test results and it has not been shown to reduce the death rate from breast cancer. Additionally, breast MRI screening is at least 10 times more expensive than screening by mammography.
WHO MAY BE AFFECTED: Women who test positive for inherited mutations in the genes BRCA1 or BRCA2 are at higher risk of breast cancer than women without these genetic mutations. Some women with these genes choose to have a prophylactic mastectomy, while others opt for rigorous screening. A woman is typically tested for the mutations only if she has risk factors, such as a family history of early breast cancer.
THE STUDY: Researchers used a computer model to simulate the life histories of women who have BRCA1 or BRCA2 mutations, incorporating effectiveness and cost estimates of screening by mammography or MRI. They then used statistical procedures to determine whether the benefits were worth the added expense.
THE FINDINGS: It is cost-effective to add annual MRI screenings for women between the ages of 35 and 54 who carry BRCA1 mutations. For BRCA2 carriers in the same age range, annual breast MRI screens are cost-effective for the subset of women whose breasts are too dense to discern details by mammography. MRI has a larger role in screening women with BRCA1 mutations because they are at greater risk for developing breast cancer and having more aggressive cancers than BRCA2 mutation carriers.
CAVEATS: As with any computer simulation, this study is only as good as the information going into the estimates. One challenge in assessing cost-effectiveness is quantifying how a woman's quality of life may be affected by aspects of screening, diagnosis and treatment. For example, the value researchers place on deferring or avoiding a prophylactic mastectomy factors significantly in determining the cost-effectiveness of MRI screenings.
STANFORD CONNECTION: All seven authors are from the School of Medicine (one is also from the Veterans Affairs Palo Alto Health Care System). Associate professor of radiology Sylvia Plevritis, PhD, is the lead author of the paper.
FIND THIS STUDY: Published in the May 24/31 issue of the Journal of the American Medical Association.
Linking cholesterol to tumorsTHE QUESTION: What makes some pediatric brain tumor cells grow?
THE DISEASE: Medulloblastoma is one of the most common brain tumors in children. About 20 to 40 percent of kids with this type of tumor die, and others may suffer permanent health problems both from the tumor and from the surgery, radiation and chemotherapy commonly used as treatment.
BACKGROUND: A signaling molecule known as "Sonic hedgehog" is important in the development of many different cell types. It induces the expression of certain genes by binding to and activating a receptor on the cell surface called Patched 1. Researchers had previously shown that about 15 percent of mice missing one of the two copies of the gene for Patched 1 develop medulloblastoma. Although these and other findings suggest that the Sonic hedgehog signaling pathway is involved in the development of medulloblastoma, they don't identify which part of the signaling pathway is out of whack in tumors.
THE STUDY: It compared levels of gene expression between mouse medulloblastoma cells and non-cancerous mouse brain cells, seeking to better define the workings of the Sonic hedgehog pathway.
FINDINGS: The study determined that many genes involved in the synthesis and uptake of sterols—a subgroup of steroids important in the formation of cell membranes and in developmental signaling—are expressed more highly in the cancer cells. The discovery was particularly interesting because sterol synthesis is required for Sonic hedgehog signaling. Researchers found that compounds that block the synthesis of cholesterol, a well-known member of the sterol family, slowed the growth of the cancer cells. The compounds also reduced the expression of a Sonic hedgehog-sensitive gene.
HOW THEY CONFIRMED IT: Adding cholesterol or a choleterol derivative back into the experiment restored proliferation of the cancer cells and the expression of the gene. Artificially inducing the expression of Sonic hedgehog-sensitive genes also restored proliferation. These findings suggest that the sterol inhibitors are exerting their effects primarily through the Sonic-hedgehog-signaling pathway.
WHY IT MATTERS: The results suggest that it may be possible to curtail the growth of medulloblastoma and other Sonic hedgehog-sensitive tumors by administering inhibitors of sterol synthesis. Statins, commonly used to lower cholesterol levels, may be one possible therapy. If so, it may be possible to treat these deadly childhood tumors with something other than surgery, chemotherapy and radiation.
THE STANFORD CONNECTION: The study was conducted by graduate student Ryan Corcoran, working in the laboratory of Mathew Scott, PhD, professor of developmental biology, of genetics and of bioengineering.
WHERE TO FIND IT: The work was published in the May 30 issue of the Proceedings of the National Academy of Sciences.
