Real World Evaluation of the Prosigna/PAM50 Test in a Node-Negative Postmenopausal Swedish Population: A Multicenter Study

SIMPLE SUMMARY: Gene expression signatures can provide important information on the risk of recurrence in patients with hormone receptor positive early breast cancer, and they can guide postoperative treatment. We have investigated how the implementation of gene-expression-based risk signatures with the Prosigna(®) test impacted patient management in Sweden. The two major conclusions of this study are that prognostic factors derived from routine pathology were poor predictors of the intrinsic subtype and the risk of recurrence score, and that gene-expression-based risk combined with clinicopathological biomarkers (tumor size, Ki67, tumor grade) spared patients from adjuvant chemotherapy, but also identified patients who would potentially benefit from this treatment. ABSTRACT: Molecular signatures to guide decisions for adjuvant chemotherapy are recommended in early ER-positive, HER2-negative breast cancer. The objective of this study was to assess what impact gene-expression-based risk testing has had following its recommendation by Swedish national guidelines. Postmenopausal women with ER-positive, HER2-negative and node negative breast cancer at intermediate clinical risk and eligible for chemotherapy were identified retrospectively from five Swedish hospitals. Tumor characteristics, results from Prosigna(®) test and final treatment decision were available for all patients. Treatment recommendations were compared with the last version of regional guidelines before the introduction of routine risk signature testing. Among the 360 included patients, 41% (n = 148) had a change in decision for adjuvant treatment based on Prosigna(®) test result. Out of the patients with clinical indication for adjuvant chemotherapy, 52% (n = 118) could avoid treatment based on results from Prosigna(®) test. On the contrary, 23% (n = 30) of the patients with no indication were escalated to receive adjuvant chemotherapy after testing. Ki67 could not distinguish between the Prosigna(®) risk groups or intrinsic subtypes and did not significantly differ between patients in which decision for adjuvant therapy was changed based on the test results. In conclusion, we report the first real-world data from implementation of gene-expression-based risk assessment in a Swedish context, which may facilitate the optimization of future versions of the national guidelines.