Mucin Markers May Play Role in Finding Breast Cancer Recurrences

At a symposium sponsored by Schering-Oncology/Biotech, 16 researchersinvolved in studies of the investigational antiestrogen agent toremifene(Fareston) discussed its potential role in the treatment of patients withadvanced breast cancer and as adjuvant therapy, as well as other breastcancer issues. Previous articles in this series appeared in January 1997, February 1997 , and March 1997

PALM SPRINGS, Calif--Although most of the mucin markers used to detectbreast cancer recurrence were developed by different laboratories at differenttimes, all recognize the products of the MUC 1 gene, Roy Beveridge, MD,of Fairfax Oncology/Hematology Associates, Annandale, Va, said at the symposium.

CA 15-3 is not specific for breast cancer, he said. Half of patientswith prostate, ovarian, or pancreatic cancer, for example, have an elevatedCA 15-3. Roughly half of patients with stage IV breast cancer have an elevatedCA 15-3, and between 10% and 20% of stage II patients have elevations ofthis marker.

Although newer versions of CA 15-3 are being developed, its value iscurrently limited because of assay variability and the wide range of levelsconsidered normal. "Unless the level doubles, it doesn't mean verymuch," he said.

CA 27-29 (Truquant BR RIA) is similar to CA 15-3 but may be more specific.The intra-assay variability is perceived to be less with CA 27-29 thanwith CA 15-3 tests, he said, and many labs have switched to the FDA-approvedCA 27-29 marker.

CA 27-29 was evaluated in a prospective double-blind multicenter clinicaltrial of about 200 patients with stage II or III breast cancer who wereclinically free of disease at the time of enrollment.

Of the 26 patients who had recurred at four years, 15 had an elevatedCA 27-29, yielding a specificity of 98% and sensitivity of about 60%. Thelead time (from tumor diagnosis to elevated CA 27-29) in patients who haddistant metastasis was six to seven months. In patients who had local regionaldisease, it was two months, presumably because the volume of disease issignificantly less in these patients.

Of 29 patients with bone pain who had negative repeat bone scans, everyone also had a negative CA 27-29. Of the three bone pain patients who hadan elevated CA 27-29, all three had documented cancer recurrence. "Sothis mucin marker may have a particular value in bony disease," Dr.Beveridge said, since patients with elevated marker levels are good candidatesfor further testing.

The test probably has less value in patients with local regional disease,he said. However, in these patients, two consecutive elevations suggestcontinued disease growth, and, in that situation, "re-starting treatmentor changing to a different regimen might be reasonable."

Within the medical community, Dr. Beveridge said, "many peoplesay, well, you've identified metastatic breast cancer seven months beforeyou would have found it by physical exam, but so what? You have no datato show that early treatment of metastatic disease improves survival."He answers that the information may be particularly useful in certain subpopulationssuch as patients with bone pain and younger patients who might want aggressivetherapy when they are first diagnosed with metastatic disease.

When a member of the audience asked if an elevated CA 27-29 is an indicationto treat the patient empirically, Dr. Beveridge said that in general itis not, "but there is a trial that is being organized right now toanswer that question." When patients in the study group have an elevatedCA 27-29, they will be given the choice of receiving empirical treatmentor continued monitoring.