SAN ANTONIO — A simple urine test for selected matrix metalloproteinases may provide a novel noninvasive means of assessing a woman's risk of developing breast cancer, Dr. Susan E. Pories reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.
Urinary levels of two biomarkers—matrix metalloproteinase-9 (MMP-9) and a disintegrin and metalloprotease 12 (ADAM12)—appear to be independent predictors of the presence of breast atypical hyperplasia or lobular carcinoma in situ (LCIS), both of which are well established predictors of increased risk of breast cancer, explained Dr. Pories of Beth Israel Deaconess Medical Center, Boston.
Dr. Pories and her coworkers had previously found that levels of MMP-9 and ADAM12 increase with more advanced disease status in patients who have breast cancer.
In the current study, she reported on urine samples obtained from 44 women with atypical ductal or atypical lobular hyperplasia, 24 with lobular carcinoma in situ, and 80 healthy controls.
For a 30-mL urine sample testing positive for both MMP-9 and ADAM12, the probability that the sample belonged to a woman with LCIS or atypical hyperplasia was 100%.
A urine sample that was MMP-9 negative but ADAM12 positive, had a 67% probability of being associated with atypical hyperplasia and a 50% likelihood that the patient had LCIS.
An MMP-9-positive/ADAM12-negative urine sample conferred a 40% chance that the patient had LCIS and a 25% chance that she had atypical ductal hyperplasia or atypical lobular hyperplasia.
And finally, a sample that proved negative for both biomarkers was associated with a zero probability of atypical hyperplasia.
The urine test has the advantages of being less invasive, less costly, and less uncomfortable than mammography. Asked how she envisions the urine test being used, Dr. Pories said in an interview that although it will never replace mammography, it could end up as a useful adjunct, serving, for example, as a tie breaker in helping to decide whether to biopsy a woman with a Breast Imaging Reporting and Data System (BI-RADS) stage 3 or 4 mammogram.
In high-risk women, the test could also be performed between scheduled mammograms in order to provide early warning of a change in status even before a mass appears.
She added that further studies with larger numbers of patients are needed to be sure the test is valid. The investigators are looking for a commercial partner to develop their assay.