Late recurrence risk in breast cancer differentiated by gene expression test

Patients at higher or lower risk for having their cancer recur elsewhere in the body more than 5 years after diagnosis can be differentiated by a gene expression test. The test measures the expression levels of 58 genes in estrogen receptor-positive breast cancers. These research results were presented at the 5th IMPAKT Breast Cancer Conference in Brussels, Belgium.

These findings show that individual risk prediction for women with these cancers is getting better, stated study author Michael Gnant, MD, of the Medical University of Vienna, Austria. He explained that metastasis after five years of follow-up is an important research issue, particularly in hormone receptor-positive breast cancer.

"Despite all great progress we have made in the treatment of this most frequent subtype of breast cancer, some patients develop metastasis many years after their initial diagnosis. Extending adjuvant endocrine therapy to prevent this is an option, but comes with substantial side effects and cost for society, and should therefore be reserved for those patients who really need it. Thus, better defining individual risk for late metastasis is an important medical and scientific need," said Gnant.

The PAM50 Risk of Recurrence (ROR) score used by the researchers in this study directly measures the expression levels of 58 different genes (50 discriminator genes and 8 controls). The research team performed the PAM50 analysis on 1,478 patients who had taken part in the ABCSG-8 trial, which ran from 1996 to 2009. They found that the PAM50 ROR score provided significant prognostic information in addition to clinical factors with respect to late distant-relapse-free survival.

After 11 years of median follow-up, of patients who were classified by the test as having low risk, 98.7% had not had a late metastasis between 5 and 10 years of follow-up, compared to 91.5% of those with a high PAM50 ROR score. This was true both for node-positive and node-negative disease.

"It makes a huge difference whether a patient looks at an individual risk of 1.3% or 8.5% between years 5 and 10. This is more than six times as much risk. Such important information may well be implemented into individual treatment decisions," said Gnant.

The researchers conclude that the PAM50 ROR score can successfully be used to differentiate patients with respect to their risk for late metastasis, in addition to established clinical and pathological risk factors. This ability to predict late metastasis may be used in the future to identify patients with endocrine-responsive breast cancer who need or alternatively who can be spared extended adjuvant therapy.
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