LAUSR

Background: The prediction of late distant recurrence (DR) is an important clinical goal for managing women with hormone receptor positive disease who have reached the end of 5 years9 endocrine treatment without recurrence. Molecular profiles have produced conflicting results for the prediction of late DR. Here, we develop and validate a simple clinicopathological tool (Clinical Treatment Score post-5 years (CTS5)) to estimate the residual risk of DR after 5 years9 endocrine treatment, which should help in discussions with patients about the potential benefits or not of continued endocrine therapy. Patients and Methods: The ATAC dataset (N=4735) of postmenopausal women with oestrogen receptor (ER) positive breast cancer treated with 5 years9 tamoxifen or anastrozole was used as a training cohort to establish a prognostic score for post-5-year risk of DR. CTS5 was based on five categories for nodal status, linear and quadratic terms for tumour size (capped at 30mm), three categories for grade, and continuous age. The validity of the CTS5 was tested in the BIG1-98 dataset (N=6711), which included postmenopausal women with ER-positive breast cancer treated with tamoxifen or letrozole (either monotherapy or sequential). Both cohorts included women who were alive and DR-free 5 years after randomization. Time to late DR, defined beginning at 5 years after ATAC or BIG 1-98 randomization, was the primary endpoint. Cox regression models estimated the prognostic performance of the CTS5. Hazard Ratios (HRs) are for a change of one Standard Deviation. Results: The CTS5 model was a significant predictor for late DR in ATAC (HR=2.47 (95% CI, 2.24-2.73), P 10% risk), identified 43% of the validation cohort as low risk, with an observed DR rate of 3.6% (95% CI 2.7-4.9) during years 5-10. Within nodal subgroups, 63% of node-negative were low risk with 3.9% (2.9-5.3) DR rate between years 5-10, and 24% having 1-3 nodes positive were low risk with 1.5% (0.5-3.8) DR rate between years 5-10. Separation of intermediate-risk from high-risk categories was also shown in the training set but improvements in calibration seem necessary for clinical utility for that assessment. Conclusion: The CTS5 is a simple tool based on information that is readily available to all clinicians. It was more accurate in its prediction of DR risk in years 5-10 than the published CTS model. CTS5 was validated as highly prognostic for late DR in the independent BIG 1-98 study. The algorithm identified a subgroup of women with either node-negative disease or 1-3 positive nodes as having less than 1% per year risk of DR who could be advised of the limited value of extended endocrine therapy. Citation Format: Sestak I, Regan M, Dodson A, Viale G, Thurlimann B, Colleoni M, Cuzick J, Dowsett M. Integration of clinical variables for the prediction of late distant recurrence in patients with oestrogen receptor positive breast cancer treated with 5 years of endocrine therapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS6-01.