Abstract P1-08-26: Morphologic characterization of tumor-infiltrating lymphocytes and its relation with pathological response in a series of breast cancer patients treated with primary chemotherapy
Authors: Falo Catalina , Azcarate Juan , Petit Ana , Vethencourt Andrea , Gonzalez Sergi Fernandez , Garcia-Tejedor Amparo , Vazquez Silvia , Perez Hector , Laplana Maria , Taco Charo , Guerra Esther , Guma Anna , Ortega Raul , Stradella Agostina , Recalde Sabela , Fernandez-Ortega Adela , Villanueva Rafael , Perez F Javier , Pla M Jesus , Campos Miriam , Perez Diana , Fernandez-Montoliu Eulalia , Obadia Veronica , Cejuela Monica , Gil-Gil Miguel , Pernas Sonia , Varela Mar , Soler-Monzo Teresa 
Published: March 2022

Introduction: Tumor-Infiltrating Lymphocytes (TILS) is a well-known predictor of response to primary chemotherapy1,2 and a prognostic factor for improved survival in different breast cancer subtypes3. We present data on the association of the level of TILs and morphologic characteristics of such infiltrate with pCR. Material and methods: A series of 477 breast cancer patients (479 tumors) treated with primary chemotherapy at Catalan Institut of Oncolgy - H.U. Bellvitge between January 2009 and December 2016. Chemotherapy consisted on anthracyclines and taxanes (plus trastuzumab if Her-2 positive disease). Levels of percentage of TILs using hematoxylin-eosin-stained sections of diagnostic core-needle biopsy were evaluated according to international guidelines in a prospectively defined retrospective analysis. Characterization of TILS consisted on identification of plasma cells, intraepithelial infiltrate vs stromal infiltrate and homogeneous vs heterogeneous infiltrate. A sub-classification using levels of TILS and heterogeneity was done for statistical purposes. Levels of TILS and their morphological characteristics were examined for their associations with pCR adjusted for predictive clinic-pathological factors, by univariate and multivariate logistic regression, statistical significance set at 0.05. A ROC curve was performed to look for a cut-point of TILs to predict PCR. Results: The mean value of TILs was 23.79% (SD, 24%). TILs were significantly higher in ductal carcinomas (39.1% vs 0%, p=0.007), grade 3 (55.2 vs 17.7%p&lt;0.001), ki 67 &gt;30 (48.8% vs 24.5%, p&lt;0.001), HER2 (56.6%) and triple negative tumors (TNBC)(56.6%) vs luminal (20%), p&lt;0.001). The level of TILS was set in 20% to predict pCR by a ROC curve (S=62.3% E=71%). Characterization of TILs found plasma cells in 41.1% of the samples, intraepithelial infiltrate in 11.2% and homogeneous infiltrate in 60.1%. Homogeneously high infiltrate was found in 20% of the samples. In the univariate analysis pCR was higher in samples with TILs &gt; 20% (15.2% vs 41.5%, OR: 3.96 [95%CI, 2.57-6.10]; P &lt; 0.001); plasma cells (OR 6.61 [95%CI, 1.51-28.8]; P=0.01), intraepithelial TILS (OR: 10.34 [95%CI, 2.22-48.01]; P =0.003), homogeneous high infiltrate (OR: 13.6 [95%CI, 3.04-60.77]; P =0.001). In luminal tumors, TILs over 20% predicted pCR (OR 12.3 [95%CI, 4.0-37.7]; P &lt; 0.001) as well as in TNBC (OR 4.32 [95%CI, 1.77-10.53]; P=0 .001) but not in those cases with HER2 positive tumors (luminalB HER2 + HER2) (OR 1.65 [95%CI, 0.88-3.07]; P=0.118). In the multivariate analyses, levels of TILs &gt; 20% were associated with higher pCR rates (adjusted odds ratio, 2.44 [95%CI, 1.48-4.01]; P &lt; .001). Conclusions: The presence of TILs over 20% at diagnosis is an independent, positive, predictive marker of pCR in early breast cancer treated with neoadjuvant chemotherapy. Interestingly, the predictive information added by TILs &gt;20% was higher in luminal and triple negative tumors compared to HER2 positive cases. Careful morphological characterization of TILS may add valuable predictive information and can be done in current pathologic laboratories with a well-trained breast cancer pathologist. References: 1.J Clin Oncol 2009; 28:105-113. doi: 10.1200/JCO.2009.23.73702.JAMA Oncol. 2015;1(4):448-454. doi:10.1001/jamaoncol.2015.08303.Lancet Oncol 2018: 19: 40-50 http://dx.doi.org/10.1016/S1470-2045(17)30904-X.

N%Age years (mean, sd)Grade*I326.7II19540.7III15152.6Ki 67≤3020442.6&gt;3027557.4Molecular subtype*Luminal A469.6Luminal B HER2 -14329.9Luminal B HER2+9219.2HER+ enriched7615.9Triple negative12225.5Pathologic responseNon-pCR35874.7pCR12125.3

Citation Format: Catalina Falo, Juan Azcarate, Ana Petit, Andrea Vethencourt, Sergi Fernandez Gonzalez, Amparo Garcia-Tejedor, Silvia Vazquez, Hector Perez, Maria Laplana, Charo Taco, Esther Guerra, Anna Guma, Raul Ortega, Agostina Stradella, Sabela Recalde, Adela Fernandez-Ortega, Rafael Villanueva, F Javier Perez, M Jesus Pla, Miriam Campos, Diana Perez, Eulalia Fernandez-Montoliu, Veronica Obadia, Monica Cejuela, Miguel Gil-Gil, Sonia Pernas, Mar Varela, Teresa Soler-Monzo. Morphologic characterization of tumor-infiltrating lymphocytes and its relation with pathological response in a series of breast cancer patients treated with primary chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-26.