Association of immune, proliferation gene signatures and stromal tumor infiltrating lymphocytes (sTILs) with outcomes in patients with stage I triple-negative breast cancer (TNBC).

Abstract

553 Background: Approximately one third of all TNBC diagnoses are stage 1. No validated biomarker is routinely utilized to guide treatment at this early stage. Methods: Samples from patients with stage I TNBC or ER-low (1-10%) breast cancer undergoing surgery at Dana-Farber/Brigham Cancer Center between 2016 and 2021 were identified. The 10-gene Core Immune Gene (CIG) signature and the 4-gene proliferation signature (both part of the TNBC-DX tool) were derived from extracted RNA. Central evaluation of sTILs was conducted at Dana-Farber, with 5% and 20% used as thresholds. All markers were tested for prediction of recurrence free survival (RFS) using the Kaplan-Meier method. Results: We identified 253 patients with stage I TNBC (n=218) or ER-low tumors (n=35) treated at Dana-Farber. Median age was 61 (31 – 85), most tumors were ductal (89%), high-grade (73%), 48% were >1 cm and 65% received chemotherapy. 5-year RFS in the overall cohort was 86.8%, with numerical variation by tumor size (T1a 100%, T1b 93.8%, T1c 81.7%, p=0.26). Gene signatures and sTILs were obtained for 117 and 123 patients, respectively (both for 110 patients), with their association with outcomes described in Table 1. Median follow-up was 3 years. A total of 20/117 patients (17.1%) had medium-high CIG score, with none experiencing RFS events prior to year 5. Similarly, no recurrence was observed prior to year 5 in 29 patients (24.8%) at the upper CIG quartile (vs 83-88% 5-year RFS in other quartiles). Worse outcomes were seen among patients in the upper quartile of proliferation (5-year RFS 83%, vs 88-100% in other quartiles). Overall, 33/123 patients (26.8%) had high sTILs (>20%) and experienced the highest 5-year RFS (97%, vs 78% if low sTILs). OS data will be presented. Conclusions: High expression of the 10-gene CIG immune signature or high sTILs are associated with numerically improved outcomes in patients with stage I TNBC that did not reach statistical significance, warranting further study as prognostic tools. 3- and 5-year recurrence free survival (RFS) according to gene signatures and sTILs. P values were obtained via Cox proportional hazard models. N 3-year RFS 5-year RFS CIG score - Low- Med-High 9720 91% (85%, 98%)100% (100%, 100%) 89% (80%, 98%)100% (100%, 100%) CIG score (quartiles)- ≤25%- 25-50%- 50-76%- >75% 49102929 94% (87%, 100%)83% (58%, 100%)87% (74%, 100%)100% (100%, 100%) 88% (74%, 100%)83% (58%, 100%)87% (74%, 100%)100% (100%, 100%) Proliferation score - Low- Med-High 5859 96% (89%, 100%)90% (82%, 99%) 90% (78%, 100%)90% (82%, 99%) Proliferation score (quartiles)- ≤25%- 25-50%- 50-76%- >75% 30292929 100% (100%, 100%)90% (77%, 100%)100% (100%, 100%)83% (68%, 100%) 88% (67%, 100%)90% (77%, 100%)100% (100%, 100%)83% (68%, 100%) sTILs- 1-5%- >5-20%- >20% 622833 94% (87%, 100%)91% (81%, 100%)97% (90%, 100%) 78% (63%, 98%)91% (81%, 100%)97% (90%, 100%)