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.

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Ovarian cancer (OC) is associated with the highest cancer-related mortality among gynecological cancers, since nearly 2/3 of patients are diagnosed with advanced stage disease which is caused by an unspecific clinical appearance and the lack of effective early detection methods. So far only histopathological and clinical prognostic factors have clinical relevance from which FIGO-stage and the postoperative residual disease have predominant importance. Early stage OC (FIGO Ia-II) has a good prognosis with survival rates of approximately 90%, provided that the tumor is macroscopically resected and an adequate surgical staging has been performed. Additionally early stage OC patients should receive an adjuvant platinum-based chemotherapy. In advanced stage OC (FIGO IIb-IV) the aim of primary surgery is a maximum cytoreduction. Additionally, postoperative treatment is performed with carboplatin/paclitaxel for six cycles. So far there are no data to support the introduction of non-cross-resistant agents, dose escalation or prolongation of therapy. The majority of advanced stage patients relapse despite optimal primary therapy. Treatment of recurrent disease follows palliative considerations and should serve symptom control and tumor regression and especially quality of life. The prognosis of recurrent disease differs extensively according to the length of the progression-free survival and response to primary platinum-based chemotherapy and is differentiated into platinum-refractory and platinum-sensitive disease. Platinum-refractory OC generally have an extensive chemoresistance against all available cytostatic agents. Various mono-chemotherapies do not exceed response rates of 20%. In contrast, platinum-sensitive recurrent OC have a much more favourable prognosis due to response rates of 30-50% with platinum-based combination therapies. Another operation seems to be only reasonable in case of platinum-sensitive recurrent disease and if the tumor can be macroscopically resected with no residual tumor The aftercare in OC should focus on the detection of recurrent disease and the detection and therapy of maintained treatment related toxicities as well as psycho-oncological aspects.

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