Behind the numbers.

There are several molecular panels used to predict the risk of distant failure after treatment of early stage breast cancer: OncotypeDX Recurrence Score (RS), PAM50, EndoPredict, and Breast Cancer Index. They do this by characterizing tumor biology, but how does tumor biology influence each test’s results? It’s commonly thought that the OncotypeDX Recurrence Score (RS) is driven by genes affecting proliferation because these genes have the highest weighting in the score. This study used an independent cohort of nearly 800 patients to compare which genes drive each of the 4 above-mentioned tests. In contrast to the other tests, RS results were most often driven by estrogen-related genes as opposed to proliferation genes. Why? In the RS, proliferation gene expression must surpass a threshold to influence the overall score, which was infrequent in the tumors typically tested. So, for many tumors, the RS appears to predict the benefit of endocrine therapy more so than the benefit of chemotherapy. TBL: Understanding the biology of prognostic molecular tests for breast cancer is key to interpreting their results. | Buus, J Clin Oncol 2020

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