ATLANTAAn immunogenic marker, TA-90, can detect breast cancers
missed by mammograms and other known markers, Rishab K. Gupta, PhD,
said at the Era of Hope: U.S. Department of Defense Breast Cancer
Research Program Meeting.
TA-90, the 90kD glycoprotein tumor-associated antigen, also has shown
promising results in tests with melanoma, lung, prostate, ovarian,
and colon cancers, Dr. Gupta said in an interview with ONI.
He estimates that 75% to 80% of breast and melanoma tumors would test
positive with a TA-90-specific immune complex (IC) detection assay,
based on studies conducted at the John Wayne Cancer Institute at the
St. Johns Health Center, Santa Monica, California.
Dr. Gupta is director of immunodi-agnosis and vice president for
education at the John Wayne Cancer Institute. Donald L. Morton, MD,
medical director and surgeon-in-chief, also was one of the authors.
The presence of this antigen in the blood can identify patients
who have early-stage cancer or residual cancer after all visible
cancer cells are gone, Dr. Gupta commented. If preliminary
results are validated in clinical trials, he predicted that a routine
blood test for the marker might become a useful adjunct to mammography.
As described by Dr. Gupta, the search for an antigen-based tumor
marker began with the hypothesis that the body would release the same
amount of antigen whether the tumor cells were together in a nodule
In theory, Dr. Gupta said, testing for the marker would detect cancer
cells that were not in a mass large enough to be picked up by
mammography or other scanning methods.
Monoclonal Antibody Developed
After documenting the presence of TA-90 in blood samples from cancer
patients, the researchers developed a murine mo-noclonal antibody to
TA-90, and then used the antibody to develop the TA-90-IC assay used
in the studies.
In one study, Dr. Guptas group matched serum samples from 106
breast cancer patients with samples from 107 healthy controls.
Significantly more of the breast cancer patients63% compared to
2.8% of the control groupscored above a 0.410 ELISA value that
the researchers set as a cut-off level for presence of the marker.
A retrospective study focused on 128 patients from a database of
breast cancer patients who were positive for TA-90 before surgery.
Serum samples were obtained 2 to 12 weeks after surgical resection
and tested for TA-90.
Fifty-two patients (41%) remained positive for TA-90 after surgery
(two consecutive serum samples above the 0.410 cut-off). Among 43
patients who later had a recurrence, 34 (79%) tested positive for the
marker when they were clinically disease free after the initial
surgery. Tests were negative for the marker in 67 (79%) of 85
patients who remained disease free.
While TA-90-IC did not catch all cases, Dr. Gupta predicted that the
marker would be useful in identifying patients who need further
If I know the tumor is expressing this marker, and the tumor is
taken out by surgery, and the blood is still positive, then I can say
the patient still has the cancer in the body somewhere, he
explained. Whatever was done by surgery was not enough.
Adjunct to Mammography
testing brought the detection rate to 96% of breast cancers (54 of
56) when it was combined with mammography in a prospective study of
138 patients (see table at right). Mammograms were positive for 50
of 56 patients found to have breast cancer at biopsy. TA-90-IC
identified four of those who escaped detection by mammography. Only
two patients (5%) slipped through both screens.
Dr. Guptas group also compared TA-90 screening with tests for
two other tumor markers, CEA and CA15-3, in 68 patients known to have
breast cancer. Results showed 81% to be positive for TA-90, 24% for
CEA, and 34% for CA15-3. When all three tests were used in
concordance, they showed abnormalities in 91% of the patients.
I dont know a single marker good enough to tell
everything, but this is certainly a step in the right direction,
Dr. Gupta said, adding that he hoped to continue working toward
clinical trials. To validate these kinds of findings, we need
to have thousands of patients.