Abstract P6-09-44: Tumor-infiltrating lymphocytes (TILs) is associated with improved overall survival in triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy (NAC)
Authors: Sampaio CdDAT , de Lima VCC , de Andrade VP , Neotti T , Tavares MC , Sessa VA , Calsavara VF , Zenun GR , Giongo AA , da Costa AABA 
Published: March 2017

Background: Recent studies suggest that the percentage of TILs is a predictive factor for response to NAC and a prognostic factor associated with long-term disease control in hormone receptor-negative breast cancer. The TILs working group's current recommendation is to evaluate stromal TILs as the principal parameter in future studies. The term lymphocyte-predominant breast cancer (LPBC) can be used as a descriptive term for tumors that contain more lymphocytes than carcinoma cells. Typically, the threshold of stromal lymphocytes for LPBC is around 50% of the stromal surface area. It is unclear if this cutoff will be used in the future as such an intense TIL infiltration in tumors has been reported to be infrequent (∼10%). Studies with TNBC have demonstrated increasingly better overall survival (OS) and disease-free survival (DFS) associated with continuous scores of TIL in patients treated with adjuvant chemotherapy. In patients treated with NAC, TILs predicted pathological complete response (pCR). Our goal was to evaluate the impact of TIL on OS in TNBC patients treated with NAC.

Methods: Data from patients with histologically confirmed TNBC treated with NAC from a single institution (A. C. Camargo Cancer Center - ACCCC), between July 2002 and November 2013, were retrospectively collected using electronic medical records. Patients with metastatic disease or in situ carcinoma at diagnosis were excluded. The density of TILs was evaluated in full-face hematoxylin and eosin-stained (HE) slides. Three blinded pathologists made the assessment of each slide, and a consensus on the TIL percentage was achieved. A cut-off of 10% for TIL percentage was employed for OS and DFS calculations, based on technical statistical maximizing log-rank test. We use this cut-off to test the association with pathological pCR rate as well. For pCR rate, we also used a cut-off of 50% (LPBC). We used Chi-square test to evaluate the association with pCR. A p-value&lt;0,05 was considered statistically significant for all tests.

Results: We identified 78 patients that fulfilled all inclusion and exclusion criteria. The median age was 42 years (range 17-70), and the clinical stage distribution was IIA (14%), IIB (22%), IIIA (19%), IIIB (33%) and IIIC (11%). 58 patients had archival FFPE blocks available and suitable for pathological analysis. Median follow-up was 4,1 years. Overall survival in 5 years in this subgroup was 62% (median not reached). 23 (39.7%) tumors had TIL&gt; 10%, however only 10 had TIL &gt; 50%. TIL &gt;10% was associated with improved OS (HR 0.33, 95% CI, 1.0 to 0.11; p = 0.04). The same cut-off was associated with better DFS, although not statistically significant (HR 0.46, 95% CI, 1.1 to 0.18; p = 0.1). The overall pCR rate was 39.6% (48% for patients with TIL &gt; 10% and 34% for patients with TIL &lt;or = 10%; p = 0.3). LPBC had similar pCR rate (40% for LPBC vs. 39% for non-LPBC), probably due to the small number of samples analyzed. pCR was associated with a decreased risk of death (HR 0.06, 95% CI, 0.008 to 0.47; p&lt;0.01).

Conclusion: We observed improved OS associated with TIL&gt;10% in TNBC patients treated with NAC. pCR was also associated with better OS.

Citation Format: Sampaio CdDAT, de Lima VCC, de Andrade VP, Neotti T, Tavares MC, Sessa VA, Calsavara VF, Zenun GR, Giongo AA, da Costa AABA. Tumor-infiltrating lymphocytes (TILs) is associated with improved overall survival in triple-negative breast cancer (TNBC) patients treated with neoadjuvant chemotherapy (NAC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-44.