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Blood test for breast cancer closer to reality. (More Accurate than Mammography).

SAN ANTONIO -- A simple blood test for breast cancer detection that's substantially more accurate than mammography is drawing closer to clinical reality.

And that's not all. The same proteomics technology being harnessed to detect breast cancer using a single drop of blood is yielding tantalizingly high-sensitivity and high-specificity tests for the diagnosis of ovarian, lung, and prostate cancers in early clinical testing, investigators reported at a breast cancer symposium sponsored by the San Antonio Cancer Institute.

Proteomics use protein-based chips and high-throughput mass spectromerry to analyze millions of combinations of cellular protein expression to identify protein pattern "fingerprints" associated with solid tumors. Patterns of protein expression reflect the deranged cellular circuitry that defines particular types of malignancy.

Unlike DNA microarray analysis, another novel molecular diagnostic technology, proteomics provides direct data on tumor and/or host interactions, explained Emanuel F. Petricoin III, Ph.D., codirector of the Food and Drug Administration and National Cancer Institute clinical proteomics program, Rockville, Md. The program is a joint translational medicine project aimed at moving proteomics from the research laboratory into clinical practice.

Working with collaborators at universities and biotech companies around the country, Dr. Perricoin and his associates have developed a protein pattern "fingerprint" for breast cancer. They tested it in a single drop of blood obtained from 117 breast cancer patients and 99 with biopsy-proved benign breast disease, all of whom had abnormal breast-imaging findings. The blood test had 90% sensitivity and 71% specificity for detecting breast cancer. 'In theory, we were able to miss breast cancer only 10% of the time while avoiding an unnecessary biopsy 71% of the rime," he observed.

Despite these encouraging data, his group's top research priority is ovarian cancer rather than breast cancer. Currently there is no good diagnostic test for early ovarian cancer. Patients are diagnosed late, and mortality is high. "If only ovarian cancer could be detected at stage I instead of much later, we could have a dramatic impact with surgery alone," Dr. Petricoin noted.

He and his coworkers have developed an ovarian cancer proteomics "fingerprint." In its latest version, the blood test has been applied to 133 ovarian cancer patients and 95 women without the malignancy. The test displayed 100% sensitivity and 100% specificity for detecting ovarian cancer.

In the setting of possible lung cancer, the goal of a peoteomics-based blood test is the same as in breast cancer: initially to use it to eliminate unneeded biopsies in patients with a false-positive or equivocal imaging study. In the more distant future, the blood test might be used instead of screening mammography or--in the case of suspected lung cancer--spiral CT.

So far the lung cancer test developed by Dr. Petricoin and his associates has been studied in 59 patients with a positive spiral CT; 19 of them had adenocarcinoma, and 40 had benign lung rumors. The blood test had 100% sensitivity and 95% specificity for detecting lung cancer.

Other groups involved in proteomics research also report progress. In a separate presentation at the breast cancer symposium, Dr. Lori L. Wilson said she and her colleagnes at Eastern Virginia Medical School, Norfolk, have developed a rest that uses four distinctive protein peaks in a drop of blood to differentiate patients with breast cancer from those with nonmalignant lesions or normal breast tissue.

In an early trial run with blood samples from 30 early-stage breast cancer patients and 30 patients with benign breast disease, the blood test had 93.3% sensitivity and 93.3% specificity for detecting breast cancer. That's better than mammography can do. The next step will be a large multicenter validation study Additional diagnostic algorithms are under evaluation, she added.

Dr. Petricoin said a national clinical trial of the diagnostic utility of his group's serum protein pattern profiling method is scheduled to begin this spring. Initially the trial will focus on using the ovarian cancer blood test in women who present with an adnexal mass; later testing may include an asymptomatic high-risk screening population. If the results holdup, the study will expand to include patients with suspected breast, lung, and prostate tumors.

He hopes to see proreomics move into clinical practice in coming years as an early diagnostic test for various cancers at a stage when they are more treatable.

Proteomics also offers potential for tailoring therapy to render it more effective. For example, profiling the status of signaling pathways in a patient's tumor might identify the most susceptible therapeutic targets.

It's also likely that knowing a patient's tumor molecular profile would enable oncologists to effectively use much lower doses of anticancer drugs in certain individuals than are now standard. And by monitoring how signaling pathways change when relapse occurs, it might become possible to combine treatments to better maintain patients in long-term remission, Dr. Petricoin observed.
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Author:Jancin, Bruce
Publication:Internal Medicine News
Date:Mar 1, 2003
Words:794
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