Abstract P1-10-04: Impact of body mass index (BMI) on the predictive and prognostic value of stromal tumor-infiltrating lymphocytes (sTIL) in triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy (NACT)
Authors: Desmedt Christine , Richard François , Jongen Lynn , Hamy-Petit Anne-Sophie , Wildiers Hans , Ardui Jan , Punie Kevin , Smeets Ann , Berteloot Patrick , Vergote Ignace , Lae Maricl , Decroze Diane , Meseure Didier , Reyal Fabien , Biganzoli Elia , Neven Patrick , Floris Giuseppe 
Published: March 2020

Abstract
Background. High levels of sTIL have been associated with an increased pCR rate after NACT. Recent experimental and human data have demonstrated that obesity is associated with T-cell dysfunction (mediated by increased expression of checkpoints PD-1, LAG3 and TIM3), herewith reducing antitumor immune response. Here, we evaluated the value of sTIL in predicting pCR and prognosis in TNBC treated with NACT according to patient’s BMI.
Patients and methods. We considered two institutional retrospective series of 452 TNBC patients treated with NACT (Leuven: n= 174, and, Curie: n= 278). Underweight patients (&lt;18.5 kg/m2) were excluded (n=6). TNBC was defined by ER (&lt;1%), PR&lt;1% and HER2 negativity. sTIL were scored centrally by an experienced pathologist (GF) on pre-treatment biopsies according to standard guidelines (Salgado Annals of Oncol 2015). In agreement with recent TNBC literature, highly infiltrated tumors were defined as ≥ 30% TIL (Loi J Clin Oncol 2019). BMI was binarized for the main analyses (lean (18.5-25 kg/m2) versus overweight & obese (≥25 kg/m2)). Associations between BMI and clinico-pathological variables were assessed using the Fisher exact test, associations with pCR (ypT0/is N0) using conditional logistic regression, and associations with disease-free (DFS) and overall survival (OS) using Cox proportional hazard regressions. Menopausal status, grade and stage were considered as adjustment variables, and center as stratification factor. An interaction term was considered between TIL and BMI. P-values were considered as significant when &lt;.05.
Results. 236 (53%), 132 (30%) and 77 (17%) patients were lean, overweight and obese, respectively. pCR was achieved in 181/445 (41%) of the patients. Median sTIL was 11% and 99/445 (22%) tumors had high sTIL. Median follow-up time was 7.63 years. BMI was associated with menopausal status (33.8% lean and 50.4% overweight & obese patients were postmenopausal, p&lt;.001), stage (30.5% lean and 41.1% overweight & obese patients were stage 2/3, p=.022), and histological grade (85.8% lean and 91.8% overweight & obese patients had grade 2/3 tumors, p=.051). BMI was not associated with sTIL (p=.910). Regression analyses revealed a statistically significant interaction between sTIL and BMI for predicting pCR both in the unadjusted (p=.024) and adjusted analysis (p=.033) (see alsoTable 1). sTIL were significantly associated with pCR in lean (ORadj: 4.24, 2.10-8.56, p&lt;.001), but not in overweight and obese patients (ORadj: 1.48, 0.75-2.91, p=.257). Exploratory analyses using the 3 BMI categories were consistent with previous results (lean ORadj: 4.24, 2.10-8.57, p&lt;.001, overweight ORadj: 1.45, 0.64-3.24, p=.372, obese ORadj: 1.51, 0.42-5.40, p=.523). Survival analyses revealed a statistically significant association of sTIL with DFS with higher sTIL being associated with better DFS in lean patients (hazard ratio, HRadj: 0.29, 0.12-0.67, p&lt;.001), but not in overweight & obese patients (HRadj: 1.72, 0.90-3.31, p=.101). The interaction term did however not reach statistical significance. Similar results were obtained for OS.
Conclusion. In this study, we demonstrated that in TNBC patients treated with NACT, high sTIL predict pCR and favorable prognosis only in lean patients.
Table 1. Unadjusted and adjusted associations with pCR in TNBC.Unadjusted OR, 95% CIAdjusted OR (95% CI)sTIL (≥30 vs &lt;30%)2.71 (1.71-4.28), p&lt;.0014.24 (2.10-8.56), p&lt;.001BMI (≥25 vs &lt;25 kg/m2)0.71 (0.48-1.04], p=.0750.87 (0.55-1.39), p=.572Menopausal status (post vs pre)0.73 (0.49-1.07), p=.1070.83 (0.54-1.26), p=.373Stage (2+3 vs 1)0.63 (0.41-0.98), p=.0390.59 (0.37-0.94), p=.026Grade (2+3 vs 1)2.42 (1.23-4.78), p=.0112.20 (1.09-4.47), p=.029
Citation Format: Christine Desmedt, François Richard, Lynn Jongen, Anne-Sophie Hamy-Petit, Hans Wildiers, Jan Ardui, Kevin Punie, Ann Smeets, Patrick Berteloot, Ignace Vergote, Maricl Lae, Diane Decroze, Didier Meseure, Fabien Reyal, Elia Biganzoli, Patrick Neven, Giuseppe Floris. Impact of body mass index (BMI) on the predictive and prognostic value of stromal tumor-infiltrating lymphocytes (sTIL) in triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy (NACT) [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 P1-10-04.