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Competition abounds, but an IVD for early breast cancer detection is still remote
Mammography has been the gold standard for early detection of breast cancer since the 1960s. But despite advances that have made the technique increasingly sensitive, mammography still has a false negative rate between 10% and 25%, according to the National Cancer Institute. Couple this with the expense and inconvenience of x-ray procedures, and the need for alternative and complementary screening assays is clear.
While no IVD test is yet available for primary screening for breast cancer, one test holds promise. The mammastatin serum assay (MSA) developed by Biotherapies Inc., the joint venture partner of Biolabs Inc. (Surrey, BC, Canada), is currently a dot-blot format test that measures mammastatin levels from blood samples. Mammastatin is a regulator protein that has been proven in preliminary research to be responsible for controlling abnormal cell growth in breast tissue. Mammastatin occurs naturally within healthy cells and is also secreted, which allows it to be assayed via the blood. Preliminary research indicates that 83% of healthy women have detectable mammastatin in their blood, while at least 90% of breast cancer patients lack the protein.
Although Biotherapies researchers are currently focusing their efforts on developing MSA as a screening test to detect women at high risk for breast cancer, early research into the potential of mammastatin as a treatment for breast cancer has so far been positive. If the protein proves to have therapeutic value, MSA could also be used to monitor breast cancer patients undergoing mammastatin therapy.
Although MSA has potential as a primary screening tool, the long-term question of where the test fits into breast cancer management is still being determined. Normal mammograms and physical examinations only detect lumps or masses of tissue. An advantage of MSA is that it detects the lack of a protein known to be associated with developing cancer cells. However, according to Ian Woods, vice president for operations at Biolabs, "At this point, it would be foolish to claim that the MSA test can replace mammograms as the standard of early breast cancer detection." With clinical trials still ongoing, Biolabs hopes to prove the utility of the MSA test in the next five to six months. "We'd like to see the test available by late 1999," adds Woods.
Other companies are also developing in vitro tests for breast cancer, but so far the indications point toward usage for detecting the recurrence or metastasis of cancer. John Glaspy, MD, a breast cancer specialist at UCLA's Jonsson Cancer Center, says he has seen "no reliable data on a blood test that can have any use in the primary diagnosis of breast cancer." But if an IVD for primary screening is something of a holy grail, there is still no shortage of tests to augment positive mammography diagnoses.
The Herceptest from Dako Corp. (Carpinteria, CA) is an immunohistochemical stain that detects her-2 gene expression in cells taken from suspected cancerous biopsies. Between 25% and 30% of newly detected breast cancer patients have the metastatic form which correlates with the presence of her-2 surface protein. "Our test measures overexpression of her-2 and the applicability of Herceptin (Genentech, South San Francisco, CA) as a therapeutic," says Sarah Sharif, product specialist for clinical diagnostics at Dako. Dako and Genentech received simultaneous approval for marketing both products earlier this year.
Chiron Diagnostics (East Walpole, MA) has also developed ACS: 180 BR, a breast cancer immunoassay. According to Mary Ellen Brandis, senior product manager at Chiron, "The ACS:180 BR assay is intended for use as an aid in monitoring progression or regression of breast cancer in response to therapy, and for detecting disease recurrence."
Looking to quantify the her-2 gene and the number of intracellular copies, Vysis Inc. (Downers Grove, IL) has applied its fluorescence in situ hybridization (FISH) core technology. The company claims that detecting the more-stable DNA molecule improves the reliability of its test, since cell-surface proteins can be altered or damaged during the preparation of tissue slides. The Pathyvision her-2 DNA probe kit is unique in that it distinguishes between true amplification of the her-2 gene and the presence of multiple copies of chromosome 17, on which the her-2 gene resides.
Breast cancer cells. (Phoyo Copyright 1999 Photodisc Inc.)
The core technology of Diagnocure (Sainte-Foy, PQ, Canada) is based on monoclonal antibodies. But according to Ursula Busse, project leader for in vitro tests, the company has developed protocols for the detection of tumor cells in blood or urine using a molecular technology called nucleic acid–based sequence amplification (NABSA). Busse says that the utility of the test is yet to be determined, but "I don't think it will replace mammography." While sensitive, the test aims at detecting micrometastases. "The detection of micrometastases in tissue samples and body fluids by molecular methods (most often done by reverse transcriptase PCR) is still in the research phase. Its true clinical value and applications still have to be determined," she cautions. The company's Diagnogene line of test kits is scheduled to be on the market this May, but will be available for research use only and not for clinical applications.
On the far horizon for breast cancer testing, researchers at the University of New South Wales (Sydney, Australia) have discovered that the x-ray diffraction patterns of hair from breast cancer patients differs from those of healthy subjects. They correlated differences in the intermolecular structure of hair with patients who tested positive for mutations in the BRCA1 gene, a gene associated with some types of breast cancer. Led by Veronica James, the team concluded that the test may lead to a simple and reliable screening method for breast cancer using a single hair. At this point, however, the major downside is the sophisticated and expensive radiation equipment required for the test.—Gary Woo
