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Breast Cancer Risk Can be Gauged by Immunohistochemical Test of Osteopontin Variants, Study Finds

NEW YORK (360Dx) – Researchers have developed an immunohistochemical test to gauge which breast lesion patients are more likely to develop breast cancer.

Imaging has allowed clinicians to spot breast lesions early, but not all lesions develop into disease. An international team of researchers, however, has developed a test to determine patients' progression risk, which they said could help stratify patients into different treatment groups. That way, those at high risk of progression could receive therapy, while those at low risk could avoid unneeded treatment.

As they reported in the British Journal of Cancer today, the University of Cincinnati's Georg Weber and his colleagues found that the expression of osteopontin variants in breast tissue correlated with risk and were prognostic for disease progression. They detected the variants with an immunohistochemistry test, which they said "has the potential to aid decision-making in the treatment of early breast lesions and improve outcome."

Osteopontin, a cytokine secreted in breast cancer as well as in other cancers, is a biomarker for both breast cancer aggressiveness and prognosis. But, as the researchers noted, the osteopontin gene product undergoes alternative splicing. Either exon 4 or exon 5 can be removed, generating osteopontin-c or osteopontin-a, respectively. These two versions of osteopontin (OPN), they said, have different functions in cancer progression.

For their immunohistochemistry test, the researchers used antibodies that recognize exon 4 — detecting OPN-a and the unspliced OPN-b form — and that recognize the splice junction within OPN-c. After staining biopsy specimens, the researchers scored the samples based on their intensity and percent positivity.

They applied this test to a cohort of 434 patients that included women with healthy breast tissue as well as women with lesions with varying risk of disease progression. Patients with ductal carcinoma in situ have a high chance, between a 30 percent and 50 percent, of disease progression, while others have a more intermediate or low risk of developing disease.

Overall, the researchers noted that OPN marker staining occurred only in breast lesions, not healthy samples, and that the intensity of staining, especially OPN-c staining, increased in samples with higher pathology-based risk of progression.

High OPN-c intensity scores, the researchers reported, were stronger predictors of progression than the other markers or scores — more than 90 percent of the women in the cohort who went on to develop breast cancer had high OPN-c intensity scores at diagnosis. While OPN exon 4 scores were less informative, the researchers noted that it and OPN-c were prognostic for later invasive disease, including among lesions typically thought to be low risk.

When combined, OPN-c and OPN exon 4 scores could also yield prognostic information. All the women in the cohort who were alive after five years had low combined OPN-c and OPN exon 4 scores, while women with high scores had a 30 percent chance of death in five years.

According to the researchers, folding in OPN-c and OPN exon 4 measurements to current diagnostic workups could help assess patients' disease. They suggested that this approach could work better than relying on the inspection of tumor margins to determine invasiveness — an approach they said is unreliable and not always possible.

"Adding measurements of OPN-c and OPN exon 4 to existing diagnostic workups of precancerous lesions holds promise for assessing invasive potential and for prognosticating cancer risk, which existing markers cannot do," Weber and his colleagues wrote.