Abstract P1-10-10: Tumor infiltrating lymphocytes (TILS) among high risk for recurrence breast cancer patients treated with tetrathimolybdate (TM)
Authors: MD Rybstein, E Nackos, N Kornhauser, T Cigler, E Andreopoulou, A Moore, M Cobham, V Fitzpatrick, S Demaria, LT Vahdat
Journal: Cancer Research (2018)

Abstract Background: Tumor infiltrating lymphocytes (TILs) evaluated in the primary tumor biopsy or surgical resection have been well established as having prognostic significance in patients with triple negative breast cancer (TNBC) and HER2+ breast cancer treated with adjuvant chemotherapy (Savas et. al, Nat Rev Clin Oncol 2016). In TNBC, stromal TILs behave as a continuous variable with every 10% increase in TIL resulting in a decrease in risk of recurrence and death. The definition of lymphocyte-predominant breast cancer (LPBC) has been used for tumors that contain 50%–60% TILs and usually have a particularly good outcome (Salgado et al, Ann Oncol 2015). Our group recently demonstrated in a phase II single arm study that tetrathimolybdate (TM), a copper-depleting agent, resulted in improved event free survival (EFS) for TNBC patients compared to historical controls. The 2-year event-free survival (EFS) for stage 2-3 and stage 4 NED was 91% and 67%, respectively. In this analysis, our goal was to explore whether the encouraging results we observed were influenced by enrolling TNBC patients with better prognostic factors at initial diagnosis, namely higher stromal TIL score, in our copper depletion trial. Methods: Archived primary breast tissue was available from 67 of the 75 patients enrolled in the phase II TM trial. The phase II study included patients with stage II TNBC or stage III or IV NED breast cancer patients, who were treated with TM for 2 years or until relapse. Here we focused on the 30 patients with TNBC. The demographic data for the patients is included in the following table. Patient DemographicsAge at diagnosisStage at study entryPrior Adjuvant or Neoadjuvant therapyNumber of prior chemotherapy regimens in metastatic setting%Tumor Infiltrating Lymphocytes504Adjuvant110543AAdjuvantn/a30563AAdjuvantn/a20513CNeoadjuvantn/a&amp;lt;5454Adjuvant230514Neoadjuvant210363CAdjuvantn/a20592BAdjuvantn/a60453CAdjuvantn/a&amp;lt;5544Adjuvant130443CNeoadjuvantn/a20474Adjuvant020563CNeoadjuvantn/a10512AAdjuvantn/a10583AAdjuvantn/a20654None25513CNeoadjuvantn/a50503CNeoadjuvantn/a30543CNeoadjuvantn/a10542AAdjuvantn/a20403CNeoadjuvantn/a40604Adjuvant160564None160554Adjuvant010633CNeoadjuvantn/a5424Adjuvant050454Adjuvant110463AAduvantn/a10523CNeoadjuvantn/a10514Adjuvant1&amp;lt;5 The number of TILs in each sample was calculated by an experienced pathologist using published criteria (Salgado et al, Ann Oncol 2015). We used TILs &amp;gt;50% to define LPBC. Results: Overall, we found that only 3/30 (10%) of TNBC patients had TILs &amp;gt;50%. In addition, 14/30 (46.7%) of TNBC patients had tumors with &amp;lt;10% TILs. The 2-year EFS for the patients with TILs &amp;gt;10% v. &amp;lt;10% was 76.9% v. 69.8%, respectively. (P=0.65) Conclusions: Only 10% of TNBC patients enrolled in the study had LPBC at diagnosis thus indicating that this cohort was not enriched for patients with immunogenic tumors. When stratified by TILs &amp;gt;10% or &amp;lt;10%, there was no statistically significant difference in EFS. Although the analysis is limited due to the small sample size, it does suggest that the amount of TILs present at initial diagnosis did not influence the overall outcome for patients treated with TM. Citation Format: Rybstein MD, Nackos E, Kornhauser N, Cigler T, Andreopoulou E, Moore A, Cobham M, Fitzpatrick V, Demaria S, Vahdat LT. Tumor infiltrating lymphocytes (TILS) among high risk for recurrence breast cancer patients treated with tetrathimolybdate (TM) [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 P1-10-10.