Abstract P6-09-10: Results of multigene assay (MammaPrint®) and molecular subtyping (BluePrint®) substantially impact treatment decision making in early breast cancer: Final analysis of the WSG PRIME decision impact study

Background: In luminal early breast cancer (EBC) with limited nodal involvement, current guidelines recommend to use multigene assays in addition to conventional clinicopathological factors for decision making regarding adjuvant chemotherapy (CT). The WSG PRIME Study prospectively evaluated the impact of the 70-gene signature (MammaPrint®) and the corresponding molecular subtype (BluePrint®) on clinical therapy decisions in EBC. Methods: WSG PRIME recruited 452 consecutive patients (pts) in 34 centers with ER+ and/or PR+ HER- pN0-1 EBC (04/15-03/16). Of the 430 evaluable pts, 309 had pN0 and 121 pN1 disease; median age was 58 years (68% post-menopausal). MammaPrint®, TargetPrint®, and BluePrint® results were provided prospectively, after therapy decisions based on clinicopathological factors and/or local IHC (ER/PR/Ki67) had been ascertained. Results: The WSG PRIME study observed a switch in CT decisions based on the multigene test results of 28.4 % (95% CI 23.3-33.4%). In 57 pts (13.3%), the decision switched from CT to no-CT, in 65 (15.1%) from no-CT to CT; in 107 (24.9%) pts a CT decision and in 201 (46.7%) a no-CT decision was maintained. Physicians strongly adhered to test results, most notably when initial CT recommendation was discordant with the test: 62/72 (86.1%) switched from no-CT to CT following MammaPrint® high risk, with 84.7% in N0 and 92.3% in N1. For MammaPrint® low risk, 56/80 (70%) switched from CT to no-CT; this percentage was similar in pN0 and pN1. Overall adherence (all pts) was 92.9% (CT) for high risk and 90.1% (no-CT) for low risk. Regarding subtype, 1/430 tumors was classified as HER2-enriched by BluePrint®; of the 6 basal-like tumors by IHC, 2 were molecularly re-classified as luminal A and 4 as luminal B. Of the 424 luminal-A/-B-like tumors by IHC, only 283 (66.7%) were subtyped concordantly by BluePrint®; 40% (61/152) of the luminal-B-like tumors were re-classified as luminal A and 29% (79/272) of the luminal-A-like tumors were re-classified as luminal B. Switches in CT decisions were strongly impacted by molecular subtype, with 142/152 (93.4%) of molecular luminal B pts eventually scheduled for CT and 247/272 (90.8%) of molecular luminal A pts for no-CT. After the test results, physicians' confidence in their therapy decision increased in 141 (32.9%) of the cases. Conclusions: In a decision impact study, the true percentage of CT saved by a prognostic test depends on cohort characteristics. Yet, the WSG PRIME study showed that the70-gene signature (MammaPrint®) and the corresponding molecular subtype (BluePrint®) strongly impacted clinical therapy decisions in EBC with up to 3 involved lymph nodes. There was a substantial discordance between clinical and molecular luminal subtypes. After receiving the test results, physicians focused their indications for adjuvant CT on MammaPrint high-risk luminal-B-like tumors. Where test results were discordant with clinical assessment, physicians mostly omitted CT in MammaPrint low risk patients. Recently, the prospective MINDACT trial had shown that this did not compromise outcome.Background: In luminal early breast cancer (EBC) with limited nodal involvement, current guidelines recommend to use multigene assays in addition to conventional clinicopathological factors for decision making regarding adjuvant chemotherapy (CT). The WSG PRIME Study prospectively evaluated the impact of the 70-gene signature (MammaPrint®) and the corresponding molecular subtype (BluePrint®) on clinical therapy decisions in EBC. Methods: WSG PRIME recruited 452 consecutive patients (pts) in 34 centers with ER+ and/or PR+ HER- pN0-1 EBC (04/15-03/16). Of the 430 evaluable pts, 309 had pN0 and 121 pN1 disease; median age was 58 years (68% post-menopausal). MammaPrint®, TargetPrint®, and BluePrint® results were provided prospectively, after therapy decisions based on clinicopathological factors and/or local IHC (ER/PR/Ki67) had been ascertained. Results: The WSG PRIME study observed a switch in CT decisions based on the multigene test results of 28.4 % (95% CI 23.3-33.4%). In 57 pts (13.3%), the decision switched from CT to no-CT, in 65 (15.1%) from no-CT to CT; in 107 (24.9%) pts a CT decision and in 201 (46.7%) a no-CT decision was maintained. Physicians strongly adhered to test results, most notably when initial CT recommendation was discordant with the test: 62/72 (86.1%) switched from no-CT to CT following MammaPrint® high risk, with 84.7% in N0 and 92.3% in N1. For MammaPrint® low risk, 56/80 (70%) switched from CT to no-CT; this percentage was similar in pN0 and pN1. Overall adherence (all pts) was 92.9% (CT) for high risk and 90.1% (no-CT) for low risk. Regarding subtype, 1/430 tumors was classified as HER2-enriched by BluePrint®; of the 6 basal-like tumors by IHC, 2 were molecularly re-classified as luminal A and 4 as luminal B. Of the 424 luminal-A/-B-like tumors by IHC, only 283 (66.7%) were subtyped concordantly by BluePrint®; 40% (61/152) of the luminal-B-like tumors were re-classified as luminal A and 29% (79/272) of the luminal-A-like tumors were re-classified as luminal B. Switches in CT decisions were strongly impacted by molecular subtype, with 142/152 (93.4%) of molecular luminal B pts eventually scheduled for CT and 247/272 (90.8%) of molecular luminal A pts for no-CT. After the test results, physicians' confidence in their therapy decision increased in 141 (32.9%) of the cases. Conclusions: In a decision impact study, the true percentage of CT saved by a prognostic test depends on cohort characteristics. Yet, the WSG PRIME study showed that the70-gene signature (MammaPrint®) and the corresponding molecular subtype (BluePrint®) strongly impacted clinical therapy decisions in EBC with up to 3 involved lymph nodes. There was a substantial discordance between clinical and molecular luminal subtypes. After receiving the test results, physicians focused their indications for adjuvant CT on MammaPrint high-risk luminal-B-like tumors. Where test results were discordant with clinical assessment, physicians mostly omitted CT in MammaPrint low risk patients. Recently, the prospective MINDACT trial had shown that this did not compromise outcome. Citation Format: Wuerstlein R, Gluz O, Kates R, Persoon M, Wasmayr M, Knauer M, Koplmüller R, Grischke E-M, Schem C, Thill M, Hasmueller S, Griesinger F, Koehler A, Otremba B, Schindlbeck C, Reimer T, Krauter J, Tome O, Otto F, Friedrichs K, Albert U-S, Gebauer G, Nitz U, Harbeck N. Results of multigene assay (MammaPrint®) and molecular subtyping (BluePrint®) substantially impact treatment decision making in early breast cancer: Final analysis of the WSG PRIME decision impact study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-10.