Abstract S6-04: Prediction of late distant recurrence after 5 years of endocrine treatment: A combined analysis of 2485 patients from the ABCSG-8 and transATAC studies using the PAM50 risk of recurrence (ROR) score
Authors: Sestak I , Cuzick J , Dowsett M , Filipits M , Dubsky P , Cowens W , Ferree S , Schaper C , Fesl C , Gnant M 
Published: August 2014

Background: Extended adjuvant endocrine therapy beyond 5 years is known to be of benefit to some oestrogen receptor (ER+) patients. Given the significant burden extended endocrine therapy presents, individual prediction of late recurrence risk would be highly valuable. We have previously shown that the PAM50 based Risk of Recurrence (ROR) score is significantly correlated with late recurrence in both the transATAC and ABCSG8 cohorts. Here, we assess the value of the ROR score for predicting distant recurrence beyond 5 years in a combined analysis of these two cohorts.

Methods: Long-term follow-up data and tissue samples were obtained from 2,485 postmenopausal women with hormone receptor positive (HR+) early breast cancer from the ABCSG-8 and transATAC trials. We used univariate and multivariate models to determine the prognostic value of ROR (with tumour size) for distant recurrence in years 5-10 in the combined dataset. Changes in likelihood ratio tests (DLR-χ2) are presented.

Results: A total of 2137 women who did not have a recurrence in years 0-5 were included in the combined analyses of late recurrence risk. In the univariate and multivariate analyses, CTS was the strongest prognostic score in the late follow-up period (ΔLR-χ2 = 95.17, ΔLR-χ2 = 61.65, respectively) in all patients. The ROR score also added significant prognostic information in years 5-10 in the univariate and multivariate analyses, but somewhat less than the CTS (ΔLR-χ2 = 66.09, ΔLR-χ2 = 32.57, respectively) (Table 1). The risk of distant recurrence at 10 years for the low risk group was 5.7% (95% CI 4.5% to 7.2%), for intermediate risk 14.6% (12.0% to 17.6%), and for high risk 29.3% (25.5% to 33.6%). Patients with a luminal A subtype had a 70% lower risk of late distant recurrence than those with a luminal B subtype (HR = 0.30 (0.21-0.43), P&lt;0.0001).

Conclusions: The results of this combined analyses showed that the ROR score added prognostic information to CTS in all patients and in all patient subgroups in the late follow-up period. The risk of distant recurrence in years 5-10 was statistically significantly different for the low, intermediate risk and high risk groups. These results suggest that the ROR score may be used to separate patients into risk groups who could be spared or could benefit from extended hormonal therapy beyond 5 years of treatment.

Hazard Ratio (HR) and changes in likelihood ratio test (DLR-χ2) for univariate and multivariate analyses according to all groups.  Univariate Multivariate* HR (95% CI)ΔLR-χ2 (P-value)HR (95% CI)ΔLR-χ2 (P-value)All patients (N = 2137)    CTS2.05 (1.80-2.34)95.17 (&lt;0.0001)1.88 (1.63-2.17)61.65 (&lt;0.0001)ROR2.88 (2.22-3.72)66.09 (&lt;0.0001)2.14 (1.65-2.79)32.57 (&lt;0.0001)Node-negative (N = 1580)    CTS2.10 (1.57-2.81)22.17 (&lt;0.0001)1.65 (1.19-2.30)8.28 (0.004)ROR2.67 (1.86-3.85)28.50 (&lt;0.0001)2.13 (1.44-3.15)14.61 (0.0001)Node-positive (N = 557)    CTS1.94 (1.58-2.37)37.48 (&lt;0.0001)1.82 (1.47-2.25)26.90 (&lt;0.0001)ROR2.72 (1.89-3.92)29.72 (&lt;0.0001)2.28 (1.57-3.30)19.14 (&lt;0.0001)HER2-negative (N = 1974)    CTS2.02 (1.76-2.32)79.67 (&lt;0.0001)1.84 (1.58-2.15)51.09 (&lt;0.0001)ROR3.02 (2.29-4.00)62.06 (&lt;0.0001)2.31 (1.73-3.07)33.48 (&lt;0.0001)*Addition of either score to each other

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S6-04.