Abstract P2-08-57: A biologic signature to predict ipsilateral breast event risk at 10 years for early breast cancer
Authors: Bremer T , Savala J , Leesman G , Wärnberg F , Sund M , Wadsten C , Whitworth PW 
Published: May 2019

Abstract
Background
Outcomes for women with early breast cancer have continually improved. A biologic signature to identify those patients that have elevated ipsilateral breast event (IBE) risk after breast conserving surgery (BCS) treated with or without radiation therapy (RT) is needed. More aggressive systemic or surgical options may be warranted for patients with elevated risk while BCS alone may be an option for very low risk patients. We report early results for a biologic signature interrogating critical pathways.
Material and Methods
This study includes patients from Uppsala University Hospital and Västerås Hospital diagnosed with early breast cancer, 20mm or less, treated surgically between 1987 and 2004. Women with lymph node metastases or treated with mastectomy or chemotherapy were excluded. A panel of biomarkers (HER2, PR, Ki67, COX2, p16/INK4A, FOXA1 and SIAH2) were assayed and scored in PreludeDx's CLIA lab by board-certified pathologists. There were 171 eligible patients with biomarker data; 131 received RT and 9 received hormone therapy.
Risk groups were calculated using biomarkers and clinical factors age and size. Absolute 10-year IBE risk was assessed using Kaplan-Meier survival analysis. Hazard ratios (HR) were determined using Cox proportional hazards analysis.
Results
There were 49 IBEs recorded. The biologic signature classified 41% of women into a low risk group. Patients in the elevated risk group had a significantly increased risk of 10-year IBE compared to those in the low risk group (Table 1). The HR for elevated vs. low risk group was 5.0 [2.2-11], p&lt;0.001, in a multivariate analysis of risk group and RT. Patients in the elevated risk group treated with BCS and RT had an 18% apparent risk difference in 10-year IBE. Patients in the low risk group had similar low 10-year risks of IBE, when treated with BCS, with or without RT. The low risk women had somewhat increased prevalence of low grade tumors (58% vs. 41%). Women with low grade and small tumors (up to 10mm) were classified into both risk groups (54% low vs. 38% elevated risk).
Table 1:10-year Risks of Local Recurrence by Risk GroupBCS without RTBCS plus RTN10-Yr local IBE Risk, 95%CIn10-Yr local IBE Risk, 95%CIBaseline4028%, [11% – 31%]13122% [12% – 24%]Low Risk Group196% [0%-14%]516% [0%-12%]Elevated Risk Group2149% [20%-68%]8031% [21% - 41%]
Discussion
A biologic risk signature identified early breast cancer patients with low and elevated 10-year IBE risks for women treated with BCS with or without RT and no chemotherapy. Approximately 40% of women were classified into a low risk group with a 0.5% IBE risk per year. Women in the elevated risk group had 3% to 5% IBE risks per year depending on treatment. Treatment for women in this observational study was neither randomized nor strictly rules based. With further prospective validation, the biologic signature identified herein may provide a tool enabling improved management for women diagnosed with early breast cancer.
Citation Format: Bremer T, Savala J, Leesman G, Wärnberg F, Sund M, Wadsten C, Whitworth PW. A biologic signature to predict ipsilateral breast event risk at 10 years for early 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 P2-08-57.