Abstract Background: We previously reported the correlation between tumor infiltrating lymphocytes (TIL) at baseline and pathological complete response (pCR) after neoadjuvant chemotherapy plus anti-HER2 agents for HER2-positive patients included in the prospective randomized CherLOB study (Dieci , SABCS 2014). Here we report the survival analysis results. Methods: The phase II neoadjuvant CherLOB study (Guarneri, J Clin Oncol 2012) randomized 121 HER2-positive, stage II-IIIA breast cancer patients to anthracyclines/taxane-based chemotherapy plus trastuzumab, lapatinib, or both. A part from endocrine therapy for hormone receptor-positive patients, adjuvant treatment was left to physicians' decision. This included trastuzumab for up to 1 year. Intratumoral (It) and stromal (Str) TIL were centrally evaluated on Hematoxylin and eosin-stained slides from pre-treatment biopsies and post-treatment surgical samples. For the present analysis, follow up was updated as of May 2015 (median follow up 68.3 months). Event-free survival (EFS) was calculated as the time interval from randomization to: recurrence, second primary cancer, death from any cause. Results: Among the 118 patients evaluable for pathological response, pCR (ypT0/is ypN0) was confirmed as a strong prognostic factor for EFS (HR 0.15, 95% CI 0.04-0.64, p=0.01). Both pre-treatment ItTIL and StrTIL evaluations were available for 105 patients, median values were 5% and 17% (interquartile range 0%-15% and 9%-40%, respectively). Table 1 summarizes the results of the survival analysis for the association of TIL with EFS. Table 1Continuous TILneventsHR95%CIpItTIL 10% increments105180.490.23-1.10.068StrTIL 10% increments105180.820.64-1.050.11Categorical TILneventsHR95%CILog-rank pItTIL above median; ItTIL below median51;545;130.390.14-1.090.061StrTIL above median; StrTIL below median52;538;100.750.3-1.90.61 A non-significant trend for better EFS with increasing It-TIL (per 10%) was observed. Patients with ItTIL above the median value had a more prolonged EFS compared to patients with ItTIL below median (5-yrs EFS rate 89% vs 76%), with borderline statistical significance for the comparison between the two groups. No difference according to StrTIL above vs below median value was observed (5-yrs EFS rate 83% vs 82%, respectively). A comparison between lymphocyte predominant (LP) tumors, as defined by the generally accepted cut-off of ItTIL and/or StrTIL >=60%, vs non-LP cases was not performed due to low number of patients (n=17) and events (n=1) in the LP group. Among the 63 patients with residual disease, ItTIL and StrTIL evaluated on the surgical sample were not associated to EFS. Conclusions: In this low-powered analysis, TIL did not provide significant prognostic information for HER2-positive breast cancer patients treated in the CherLOB study. However, a non-significant trend suggests a positive correlation between increased levels of It-TIL and better EFS. The evaluation of immune gene expression signatures and their correlation with survival is ongoing, results will be available for the meeting. Citation Format: Dieci MV, Bisagni G, Cagossi K, Generali DG, Sarti S, Piacentini F, Conte P, Guarneri V. Survival analysis of the prospective randomized Cher-Lob study: Correlation with tumor infiltrating lymphocytes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-08-03.