Abstract P5-08-13: Tumor infiltrating lymphocytes and pathological response are prognostic biomarkers in inflammatory and non-inflammatory breast cancer
Authors: Kaufman PA , Arias-Pulido H , Colpaert C , Chaher N , Qualls C , Marotti JD , Vermeulen P , Dirix L , van Laere S , Kuppusamy P 
Published: May 2016

Background: Tumor-infiltrating lymphocytes (TILs) have been associated with pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) as well as disease-free (DFS) and overall survival (OS) in certain breast cancer subtypes. pCR has been shown to be predictive of long-term outcome in several neoadjuvant studies and is therefore a potential surrogate marker for patient outcome. The aim of this study was to determine whether TILs and pCR can be used as a prognostic biomarker in inflammatory and non-inflammatory breast cancer.

Materials and Methods: Stromal lymphocytic infiltration (strTILs), defined as the percentage of tumor stroma containing infiltrating lymphocytes (lymphocyte predominant breast cancers (LPBC) cut-off: ≥50%), and pCR, defined as the absence of any residual invasive cancer on the resected breast specimen and all sampled ipsilateral lymph nodes following completion of NACT, were evaluated in 383 (221 Inflammatory (IBC) and 162 non-IBC Locally-advanced (LABC)) breast cancer patients. Tumors were categorised into molecular subtypes and Ki-67 status based on immunohistochemistry. Correlations with clinico-pathological variables, breast cancer-specific (BCSS) and disease-free survival (DFS) were made.

Results: strTILs were present in all patients (median: 15%, IQR: 5% to 30%). There was no difference in the frequency of strTILs between IBC and LABC cases. Thirty three (15%) IBC and 18 (11%) LABC tumors were LPBC. strTILs were significantly more frequent in triple negative (TNBC) (median, 25%) than in HER2+, Ki-67-high (15% for both) and ER/PR+ (10%)(p&lt;0.001; Kruskal-Wallis One Way Analysis of Variance on Ranks). There was a significant association of strTILs with pCR (p&lt;0.001). strTILs median was 27.5%, 15% and 10% for pCR, partial response and no response, respectively (p&lt;0.001). pCR was obtained in 4 (9.1%) of patients with strTILs &lt;10%, in 25 (56.8%) of patients with strTILs between 10 and 40% and in 15 (34.1%) of patients with strTILs &gt;40% (p=1.09E5). strTILs did not predict either DFS or BCSS in the overall breast cancer population. pCR was negatively associated with ER+ (p=0.002), positively with TN (p=0.02) and strongly associated with both DFS & BCSS (p&lt;0.0001, for both). Multivariate analysis showed that, in IBC patients, pCR (p&lt;0.0001) and lymph node rate (p=0.034) were independent predictors for DFS and pCR (p&lt;0.0001), lymph node rate (p=0.034) and LPBC (p=0.024) were independent predictors for BCSS. In LABC, DFS was independently predicted by pCR (p&lt;0.0001) and LPBC (p=0.042) and BCSS by pCR (p&lt;0.0001), LPBC (p=0.005) and ER (p=0.029). LPBC was associated with negative outcome in both IBC and LABC cases.

Conclusion: strTILs showed a strong association with TNBC tumors and with pCR. pCR is a strong prognostic factor for both IBC and LABC. The negative association of LPBC with outcome is unexpected and warrants additional studies.

Citation Format: Kaufman PA, Arias-Pulido H, Colpaert C, Chaher N, Qualls C, Marotti JD, Vermeulen P, Dirix L, van Laere S, Kuppusamy P. Tumor infiltrating lymphocytes and pathological response are prognostic biomarkers in inflammatory and non-inflammatory breast cancer. [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 P5-08-13.