Abstract P5-06-13: Factors associated with twenty-year (y) risks of breast cancer-specific mortality (BCSM) for locally-advanced breast cancer (LABC) in the surveillance, epidemiology, and end results (SEER) registry
Authors: Leone Jose P , Leone Bernardo A , Hassett Michael J , Leone Julieta , Freedman Rachel A , Tolaney Sara M , Winer Eric P , Vallejo Carlos T , Lin Nancy U 
Published: March 2020

Abstract
Background: Patients (pts) with LABC have a high risk of early recurrence and death. The risk of late BCSM in pts with LABC is unclear. Recent studies have shown that the risk of BCSM persists beyond 5 y (Pan, NEJM 2017); however, pts with LABC as well as those with hormone receptor (HR)-negative disease have not been studied. The aims of this study were to report on population-based long-term risks of BCSM, and the risks of BCSM conditional on having survived 5 y, among pts with LABC. In addition, we aimed to identify factors associated with late deaths from breast cancer.
Methods: We evaluated women with LABC (T3 or T4 [any N] or N3 [any T], M0 disease), diagnosed between 1990 and 2005, reported to SEER. HR status was known for all pts, but HER2 was unavailable. Pts with another primary tumor either before or after breast cancer were excluded. The dependent outcome is based on the cause-of-death recode variable from SEER (which can include disease or treatment-related deaths). Patients with non-cancer cause of deaths were censored. We used Kaplan-Meier analyses to determine the effect of baseline variables on cumulative risks of BCSM, estimated the annual rate of events per 100 person-years, and performed unadjusted Fine and Gray regressions for T3/T4 pts and for N3 pts stratified by HR status.
Results: We included 24,082 pts (median follow-up = 7.16 y). Of all breast cancer deaths, the proportion that occurred after 5 y was 46% for HR+ vs 13% for HR- (p&lt;0.001), the proportion after 10 y was 13% vs 2% respectively (p&lt;0.001). The table shows risks of BCSM by HR, N and T status, and annual event rates. The cumulative risk of BCSM in y 5-20 ranged from 10.2% in HR- T3/T4,N0 to 59.4% in HR+ T3/T4,N3. Conditional on having survived 5 y, unadjusted hazards of BCSM among T3/T4 pts were the following: T3/T4 HR+ N3 vs N0 (Hazard ratio [HzR] 3.9; 95% confidence interval [CI], 3.4-4.5); T3/T4 HR- N3 vs N0 (HzR 3.6; 95% CI, 2.7-4.7). Unadjusted hazards of BCSM among N3 pts were the following: N3 HR+ T4 vs T1 (HzR 1.5; 95% CI, 1.3-1.8); N3 HR- T4 vs T1 (HzR 1.8; 95% CI, 1.3-2.7).
Conclusions: Among pts with LABC, event rates within 5 y are high, in both HR+ and HR- pts. Beyond 5 y, BCSM still depends on traditional clinicopathologic factors and more late events occur in HR+ disease than in HR- disease. The observed late events lead to an extremely high cumulative risk of BCSM by y 20 in both HR+ and HR- LABC.
BCSMAll-cause mortality% Event-FreeAnnual rate (%)Cumulative risk (%)Cumulative risk (%)at 5 yat 10 yy 5-&lt;10y 10-&lt;15y 15-20y 5-20y 0-20y 0-20HR status among N3HR+N366.345.57.85.03.554.970.179.2HR-N338.931.04.70.91.027.371.878.0Nodal status among T3/T4HR+N090.281.82.01.40.617.125.256.6N179.866.53.72.41.431.245.164.0N271.251.86.54.13.148.163.176.2N356.936.99.06.03.459.476.983.8HR-N075.571.31.20.30.710.232.251.0N156.449.32.80.80.418.554.167.1N238.831.54.41.21.428.172.180.8N328.820.86.80.91.034.681.285.1Tumor size among N3 onlyHR+T175.956.76.04.32.647.660.271.0T268.446.18.14.94.156.370.179.7T361.740.98.55.83.758.974.781.0T449.730.910.26.32.660.280.288.3HR-T151.141.54.30.81.527.062.769.4T241.934.83.81.00.722.967.775.9T333.325.75.30.70.626.275.479.0T424.616.28.81.43.060.590.393.9
Citation Format: Jose P Leone, Bernardo A Leone, Michael J Hassett, Julieta Leone, Rachel A Freedman, Sara M Tolaney, Eric P Winer, Carlos T Vallejo, Nancy U Lin. Factors associated with twenty-year (y) risks of breast cancer-specific mortality (BCSM) for locally-advanced breast cancer (LABC) in the surveillance, epidemiology, and end results (SEER) registry [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-13.