The Lynx Group

A New Multigene Score Identifies Women with ER-Positive Breast Cancer at Risk for Late Metastases

February 2013, Vol 4, No 2

San Antonio, TX—A multigene score called EndoPredict can help to identify women with estrogen receptor (ER)-positive/HER2-negative breast cancer who are likely to develop metastatic disease in the long-term. EndoPredict is different from other multigene assays in its ability to predict late, rather than earlier, metastases, noted lead investigator Peter C. Dubsky, MD, Associate Professor, Department of Surgery, Medical University of Vienna, Austria, who presented results of a recent study at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium.

Oncotype DX and other predictive tests that rely on genetic signatures are used to predict earlier recurrence within the first 5 years,” Dr Dubsky said. “It is important to be able to predict risk of late recurrence for ER-positive breast cancer, because after 5 to 10 years of follow-up, mortality rates are higher for ER-positive than for ER-negative breast cancer,” Dr Dubsky noted.

The test is not yet approved in the United States. If these results are validated, then a low EndoPredict score could indicate the women who are able to forgo extended antihormonal therapy.

Unlike other multigene tests that are based solely on the molecular fingerprint of a tumor, the EndoPredict score factors in tumor biology data that are derived from tumor size and nodal status along with gene expression for 8 genes (3 proliferation genes and 5 ER-dependent genes) and 3 reference genes, similar to the techniques used in the Oncotype DX assay.

Study Results
The study was conducted on paraffin-embedded tumor tissue from 1702 postmenopausal women with ER-positive/HER2-negative breast cancer who participated in 2 randomized trials, the Austrian Breast Cancer Study Group (ABCSG)-6 and ABCSG-8. Of the total women, 33% had node-positive disease. None of the women received adjuvant chemotherapy, but all of them were treated with some form of hormonal therapy for 5 years, including tamoxifen (Nolvadex) alone or a sequence of tamoxifen and an aromatase inhibitor. The median age was 64 years.

“The entire cohort was low-to-intermediate [clinical] risk,” Dr Dubsky stated.

Using a predefined EndoPredict clinical score that combined the EndoPredict with nodal status and tumor size, 64% of the patients were determined to be at low risk for distant metastases according to a low EndoPredict score; 98.2% of these women were free of distant metastases at 10 years and were 5 times less likely to remain free of distant metastases at 10 years than the 33% of women with a high EndoPredict score.

Further analysis showed that the proliferation genes added independent negative prognostic information for early recurrence, whereas the genes associated with ER signaling added independent prognostic information for late recurrence.

Clinical Implications    
Discussing the importance of the findings, Dr Dubsky noted, “We currently have around 20,000 women in ongoing extended/late endocrine therapy clinical trials….We see very low rates, and the efficacy data of these trials is unlikely to make individual decisions for women very simple.” He believes that “gene expression data may help establish patient subgroups with a very excellent prognosis and thus facilitate the therapeutic choice.”

EndoPredict is currently available for diagnostic use in Austria and Switzerland. Expanded studies are ongoing.

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