Abstract P1-17-05: The impact of clinical risk assessment versus PAM-50 ROR score on prognosis and therapeutic decision making in patients with hormone-receptor positive early stage breast cancer
Authors: Y Devyatko, M Filipits, R Greil, M Balic, Z Bago-Horvath, C Singer, F Fitzal, G Steger, B Gray, S Ferree, C Fesl, L Soelkner, G von Minckwitz, M Gnant
Journal: Cancer Research (2019)

Abstract Background: Therapeutic recommendations for adjuvant treatment of hormone-receptor positive breast cancer patients depend on the individual recurrence risk. A number of genomic assays introduced to achieve this goal, but it's still questioned if they actually offer superior risk assessment compared to traditional risk evaluation by experienced clinicians. This study was designed to compare the prognostic accuracy of PAM-50 to clinical judgment. Methods: Based on the real data of a large adjuvant trial cohort (ABCSG-8, postmenopausal HR positive breast cancer patients), we created online-questionnaires including demographic, histological, and local-therapy details, with and without results of PAM50 ROR score. Out of 14 international breast cancer experts asked for individual patient's risk evaluation (low, intermediate, high) and therapy recommendations, 9 completed the questionnaire. Patient data were described by Kaplan-Meier estimates of distant disease free survival (DDFS) stratified by risk group. Cox regression models were compared using the Akaike Information Criterion (AIC). Results: 10 years DDFS and hazard ratios for distant recurrences stratified by risk-group as estimated giving in Table 1: 10 years DDFS and hazard ratios for distant recurrences stratified by risk-group as estimated Low riskIntermediate riskHigh risk n (%)10y DDFS,%(95%CI)n (%)10y DDFS,%(95%CI)n (%)10y DDFS, %(95%CI) HR(95% CI) HR(95% CI) HR(95% CI)Clinical only: AIC 817.6269 (43)93.0(89.8-96.2)289 (46)89.7(85.9-93.5)73 (11)76.6(66.1-87.1) 0.68(0.39,1.20) 1 2.57(1.41,4.65)PAM50 ROR: AIC 804.8241 (34)96.5(93.1-99.1)210 (33)89.2(84.7-93.7)207 (33)82.5(76.9-88.2) 0.27(0.11,0.62) 1 1.66(0.99,2.78)Combined: AIC 813.4232 (37)95.7(93.0-98.5)282 (45)87.8(83.7-92.0)117 (18)81.7(74.2-89.2) 0.42(0.22,0.84) 1 1.90(1.11,3.24) Adding genomic information to clinical risk factors leads to escalation of therapeutic recommendations (i.e. additional chemotherapy, extended adjuvant endocrine) in 20% of patients, and de-escalation in 13% of patients. Conclusions: Clinical judgment accurately identified the patients at high risk of relapse, but was clearly inferior to multi-genomic testing using the PAM-50 ROR score in differentiating low from intermediate risk. Particularly when avoiding unnecessary escalated therapy is the strategic goal, the addition of PAM-50 testing to clinical judgment offers improved accuracy in predicting low vs. intermediate risk of breast cancer recurrence. Citation Format: Devyatko Y, Filipits M, Greil R, Balic M, Bago-Horvath Z, Singer C, Fitzal F, Steger G, Gray B, Ferree S, Fesl C, Soelkner L, von Minckwitz G, Gnant M. The impact of clinical risk assessment versus PAM-50 ROR score on prognosis and therapeutic decision making in patients with hormone-receptor positive early stage breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-17-05.