nd01.JPG (11286 bytes)Discovery may link more genes to breast cancer susceptibility
Researchers investigating the rare childhood condition Faconi anemia believe they have discovered six more genetic errors that increase an individual’s chances of developing breast cancer, potentially quadrupling the number of identified susceptibility genes from two to eight. In a study published on June 13 on the Internet edition of the journal Science, investigators at Dana-Farber Cancer Institute and Children’s Hospital Boston report that an error in any of six genes identified can increase an individual’s chances of developing breast cancer.

     Currently, there are two known breast cancer susceptibility genes, commonly referred to as BRCA1 and BRCA2. “Just as women today can be tested for BRCA1 and BRCA2 mutations to determine if they have an inherited predisposition for breast cancer, testing for mutations in these other six genes may soon become a routine part of gauging inherited breast cancer risk,” said the study’s senior author, Alan D’Andrea, M.D., of Dana-Farber. “Women and their doctors can then use the information in deciding how to keep that risk at a minimum.” Women with mutated BRCA genes face a 59- to 85-percent breast-cancer risk, and a 15- to 65-percent ovarian-cancer risk.

     The finding of these new susceptibility genes may lead to the development of expanded screening and eventually more targeted treatments for breast cancer. According to D’Andrea, “This work is a prime example of how research into rare conditions can lead to better diagnosis and treatment for people with far more common diseases.” The discovery of the breast cancer susceptibility genes grew out of more than 10 years of research into a condition that affects only 500 families in the U.S. Children born with Fanconi anemia typically develop early bone marrow failure, but if they are able to survive into young adulthood, they are at high risk for leukemia, as well as tumors in the brain, head, neck, breast, colon and other parts of the body.

     Understanding the chain of events that activates the genetic mutation causing Fanconi anemia is what led to the discovery of the link between the six genes and breast cancer. When any of the six genes is damaged, five of the Fanconi genes organize to produce a protein complex that activates a sixth gene. The sixth gene, called D2, in turn initiates production of a protein that moves near BRCA1, which is designated to help repair damaged DNA. If there is an error in BRCA1 or its repair partner BRCA2, DNA damage can accumulate and  turn cells cancerous.

     Because of the proximity of the D2 protein to BRCA1 and BRCA2, D’Andrea and his colleagues thought there might be an association between the six genes that cause Fanconi anemia and the known breast-cancer genes. By studying a small group of children who have Fanconia anemia but don’t have mutations in the six Fanconi genes, Dr. D’Andrea and his colleagues learned that there were mutations in each of those patient’s BRCA2 genes.

     Suspecting the connection between Fanconi anemia genes and breast cancer genes, D’Andrea gave a sample of breast cancer cells to a specialist in cell genetics, who identified them as Fanconi anemia. Similarly, a sample of Fanconi anemia cells was given to a lab whose director, according to D’Andrea, said, “These samples must be mislabeled. They’re breast cancer cells.”

     Each year in the U.S. there are 180,000 cases of breast cancer, most with unknown cause. It is known, however, that up to 10 percent of breast cancers are inherited, and 75 percent of those demonstrate a mutation in one or both of the BRCA genes. The six new genetic markers may further explain a portion of the remaining 25 percent of inherited cases, as well as other unexplained cases of cancer that could be linked to defects in these genes that interfere with a cell’s ability to repair itself.

National advisory panel broadens recommendations for smallpox vaccine, but rejects proposal to offer vaccine to all Americans
A 14-member expert panel convened by the CDC has advised that the national policy on smallpox vaccination be broadened to include only the estimated ten to twenty thousand health care and law enforcement workers who would be directly responsible for investigating and treating initial suspect cases of smallpox. Currently, only scientists working with vaccinia viruses in a laboratory receive the vaccination. The idea of reinstating mass vaccinations was rejected by the panel.

     In light of the anthrax attacks of last fall and the undetermined threat of further bioterrorist attack, the Advisory Committee on Immunization Practices (ACIP) was asked whether the vaccine should be available to all Americans if they want it, or limited to certain groups such as health and emergency-response workers. The panel’s recommendations call for each state to identify the individuals on a pre-designated response team who would receive immunization. A diagnostic laboratory scientist is mentioned as a position that might be included on a response team.

     The recommendations do not call for immunization of all hospital workers, only those involved in direct care of smallpox patients.

     The smallpox vaccine is unlike other immunizations in that it can lead to serious and potentially fatal complications not only in the recipient, but also in people with whom the vaccinated person comes in contact, through the vaccinia scab. Immunocompromised people are at greatest risk of complication.

     Vaccinia immune globulin (VIG) derived from the blood of previously vaccinated individuals can modify some complications of the vaccine, but there is only enough of that treatment for approximately 600 patients, or the expected number of adverse reactions from vaccination of 4 to 6 million people. The panel weighed the low risk of bioterrorist attack against the risk of a serious adverse event from receiving the vaccine coupled with the relative scarcity of VIG. The panel’s recommendations are based on current knowledge, with the understanding that any change in risk would lead to a rapid change in policy.

     The experience of the anthrax attacks showed that stockpiles (in this case of vaccine) could be deployed anywhere in the United States within 12 to 24 hours. The CDC’s recommendations rely on its strategy of surveillance and ring vaccination, in which individuals identified with smallpox would be quarantined, and their close contacts would receive smallpox vaccine after exposure to reduce the spread of illness. There is no known effective treatment for the disease.

FDA clears two glucose test meters for use with personal digital assistants
     The FDA has cleared for marketing two glucose test meters used with personal digital assistants (PDAs). The devices will allow people with diabetes to more easily track and manage their blood sugar levels through use of computer technology. The products are the FreeStyle Tracker Diabetes Management System, made by TheraSense, Inc., of Alameda, Calif., and the Accu-Check Advantage Module, made by Roche Diagnostics Corp., of Indianapolis, Ind. The products, which have two components with associated software, integrate parts of each company’s currently marketed glucose meters and test strips with a Handspring Visor PDA.

     To use, the patient inserts a glucose meter module into the hand-held computer. The user then inserts a test strip into the meter, collects a blood sample, and places it onto the test strip. The hand-held computer reads the glucose levels from the measurement module, displays the results, and stores the information in an electronic database. The test results can also be uploaded onto a personal computer.

     In addition to measuring and tracking glucose levels, the new systems allow users to track a variety of other data that may affect their health, such as insulin usage, food intake, exercise, and medicine.

     The products were cleared under the FDA’s “Special” 510k review process. This alternative approach is used for faster review of modified versions of already cleared medical devices.

nd01.JPG (11286 bytes)New testing method provides faster detection of congenital syphilis in newborns
     In a June 5, 2002 article in The New England Journal of Medicine, two researchers from UT Southwestern Medical Center in Dallas, Tex., report on the development of two blood tests to diagnose congenital syphilis in newborns. The IgM immunoblotting test detects neonatal antibodies to syphilis, while the PCR test detects the DNA of the syphilis organism. According to Dr. Pablo Sanchez, professor and senior author of the study, “This is the first study to document the presence of the syphilis spirochete (bacteria) in the cerebrospinal fluid of infected infants. Thus we are the first to accurately assess diagnostic evaluations of infants for the possibility of central nervous system invasion.”

     The combination of tests will allow for faster, more accurate diagnosis and aid in the selection of appropriate treatment regimens. The chance of a mother with syphilis infecting her fetus is between 60 and 80 percent. Until now, the most accurate lab test required a three-month incubation period. As a universal precaution, infants born to infected mothers were hospitalized for a 10-day regimen of two to three penicillin doses each day. In the study, the combination of tests on newborns detected 100 percent of the cases of CNS infection, most at 1 day of age. The accuracy of this testing method would allow one dose of long acting penicillin to be used for infants showing no sign of CNS invasion.

New processing technique increases smear sensitivity for TB identification
New data released by the CDC suggest that processing sputum samples with the detergent C18-Carboxypropylbetaine 24 hours prior to performing the traditional acid-fast bacilli (AFB) smear staining could identify more cases of TB. In a study conducted among 344 prospective Vietnamese immigrants, the combined method identified 30 percent more cases of infectious TB. Researchers stressed the need for further evaluation and refinement of the test prior to widespread use; the test also increased false positives. Noted, however, were the implications for reducing TB in the U.S., where two-thirds of cases are among immigrants from Mexico, the Philippines, Vietnam, China, India, Haiti or South Korea. A key strategy for reducing infection here is to improve diagnosis of active TB disease in the immigrant’s country of origin, where the vast majority of infections are acquired.

     Each specimen in the CB-18 study was initially analyzed using the direct AFB staining method, and then split in half – one half was cultured, while the other half was treated with CB-18 for 24 hours before being processed with the traditional staining method. While the process increased sensitivity by 30 percent, there was a 10 percent reduction in specificity. A follow-up study is in progress to investigate the nature of the loss in specificity as a result of the CB-18 method.

Roche acquires broad HPV patent portfolio from Institut Pasteur
Roche Diagnostics, of Basel, Switzerland, and the Institut Pasteur, of Paris, France, have announced that Pasteur has assigned a broad portfolio of patents pertaining to the Human Papillomavirus (HPV) to Roche for an undisclosed sum. With these assignments, Roche now has access to one of the most extensive range of HPV subtypes in the diagnostics industry, from which it can develop and commercialize molecular diagnostic products for the early detection of HPV, the leading cause of cervical cancer.

     Scientists have identified more than 100 subtypes of HPV. Approximately one-third of HPV subtypes are spread through sexual contact, making it one of the most common sexually transmitted infections (STDs). In 2001, worldwide HPV molecular diagnostic sales were approximately US $21 million. The total market potential for HPV molecular tests, if adopted as a primary screening test for cervical cancer, is estimated to exceed US $600 million annually by year 2010.

     “HPV represents the next significant molecular target for us after our involvement in the blood screening market,” said Heino von Prondzynski, head of Roche Diagnostics Division. “The unique association of HPV with cervical cancer, combined with the benefits of screening, early intervention and available treatments, make this an ideal product for the diagnostics market.”

     “We are delighted to be entering into this arrangement with Roche,” commented Philippe Kourilsky, Executive President, Institut Pasteur. “It is clear to us that Roche has made a long-term commitment to advancing the state of testing not only for this highly prevalent sexually transmitted disease, but overall in the field of molecular infectious disease diagnostics. This is of great importance for Institut Pasteur since we are committed to contributing to the improvement of public health worldwide.”

nd03.JPG (12745 bytes)FTC seeks to block Cytyc’s acquisition of Digene
In a unanimous decision, the Federal Trade Commission (FTC) voted on June 24 to seek an injunction to stop Cytyc Corporation of Boxboro, Mass., from acquiring Digene Corporation of Gaithersburg, Md. Cytyc manufactures the ThinPrep liquid Pap test, controlling 93 percent of the liquid Pap market in the U.S., and nearly two-thirds of the U.S. Pap test market overall. The only other company currently producing and selling an FDA-approved liquid Pap test in the United States is TriPath Imaging of Burlington, N.C. Other companies have developed products, but have not yet proceeded through clinical trials.

     Digene is the only company in the U.S. selling a DNA-based test for the human papillomavirus (HPV), which is believed to be the cause of nearly all cases of cervical cancer. Currently, Digene’s test is used as a follow-up to inconclusive Pap tests, but the role of its HPV testing is set to expand.

     Digene’s HPV test uses a residual sample from a liquid Pap test, a method that requires the liquid Pap manufacturer to get FDA approval for running the HPV test from its media. This requires Digene to cooperate with a manufacturer in the FDA approval process, and to provide a manufacturer access to the Digene product once approved. The FDA contends that by purchasing Digene, Cytyc would be in a position to eliminate competition by limiting cooperation and access to Digene’s HPV test.

     The proposed acquisition would also eliminate future competition to Cytyc from Digene itself. In the next four to five years, the FDA is expected to approve HPV testing as a stand-alone primary cervical cancer screening tool that could be used in lieu of Pap testing, particularly for women over the age of 30.

     "This merger as proposed raises serious competitive concerns within the highly concentrated market for this important diagnostic tool," said Joe Simons, director of the FTC’s Bureau of Competition. "As a result of the proposed acquisition, it is likely that prices would increase, product innovation would suffer, and ultimately, patient care would be compromised."

IMPAC Medical Systems acquires Intellidata LIS company
IMPAC Medical Systems, Inc., a provider of integrated clinical and administrative management systems for cancer specialists, announced the acquisition of Intellidata, Inc., a clinical Laboratory Information System (LIS) supplier for medium-to-large multi-site clinics, small-to-midsize hospitals, and independent reference laboratories.

     The acquisition of Intellidata will extend IMPAC’s Multi-Access oncology management system to include IntelliLab, Intellidata’s LIS that’s capable of interfacing to laboratory devices. The result will be seamless reporting of laboratory results in IMPAC’s electronic medical record (EMR), and an LIS solution that addresses both the clinical and business needs of the cancer specialist. IMPAC will continue to support the import of lab data from any LIS via the HL7 format; however IntelliLab provides IMPAC customers with an integrated LIS solution and immediate access to critical lab values at the point-of-care.

     “IMPAC chose Intellidata as its LIS solution because the system provides sophisticated clinical analysis, connects to virtually any lab device, and supports the business requirements of the cancer center,” said Joe Jachinowski, president and CEO of IMPAC.

     Will Campbell, president of Intellidata added, “Intellidata features, such as Medicare Medical Necessity checking and ‘Keyword’ ordering, facilitate the laboratory ordering and billing process; while integration with IMPAC’s EMR expedites results reporting and review.”

nd04.JPG (17844 bytes)New test distinguishes aggressive from less aggressive prostate cancers
According to research at the University of Minnesota, published in the July 15, 2002 issue of Cancer, a simple test can be used to identify patients with the most aggressive prostate cancers, even among patients whose tumors are at the same stage. The new test was developed by cancer researcher Akhouri Sinha, a professor of genetics, cell biology, and development, faculty member of the University of Minnesota Cancer Center and research scientist at the Minneapolis Veterans Affairs Medical Center, and his colleagues.

     Cancer cells produce a high level of an enzyme called cathepsin B (CB). This enzyme destroys proteins in the connective tissue that holds cells in place, allowing the cancer cells to invade surrounding tissues and escape to blood vessels. Cells also produce natural inhibitors of CB called stefins. The researchers believed that a balance in favor of CB would produce more aggressive cancer, while higher stefin levels would make cancer less aggressive.

     Working with samples from 97 prostate cancer patients and eight patients with a benign enlargement of the prostate, researchers found that patients whose cancer had spread to one or more pelvic lymph nodes had a significantly higher ratio of CB to stefin A. According to Sinha, “The ratio of CB to stefin A reveals differences in tumors that are not visible under the microscope. If this test were done on tumors of newly diagnosed patients, we would have an indication of which cancers were most aggressive, and we could give those patients aggressive treatment. Those patients whose tumors show ratios of one, or less than one, may require less aggressive treatment. This approach could also be used for breast and colon cancer.”