Abstract P1-10-11: Pathological complete response after carboplatin-based neoadjuvant chemotherapy in triple negative breast cancer: The importance of stromal tumor infiltrating lymphocytes as a predictive biomarker
Authors: Walsh Elaine M , O'Loughlin Mark , Shalaby Aliaa , Webber Mark , Kerin Michael J , Glynn Sharon A , Callagy Grace , Keane Maccon M 
Published: March 2020

Abstract
Background: Lymphocyte predominant breast cancers (LPBC) account for 5-30% of TNBCs; 65-80% of TNBCs have low/moderate levels of sTILs and 15-20% have no lymphocyte infiltration. TNBCs with high stromal tumor infiltrating lymphocytes (sTILs) have higher rates of pathological complete response (pCR) with anthracycline-taxane (AT) neoadjuvant chemotherapy (NACT), but the effect of carboplatin (Cb) is unclear. In GeparSixto, Cb increased pCR rates in LPBC but there was no interaction between LPBC and Cb in TNBCs. This study examines the predictive role of sTILs in TNBCs, focusing on the association between sTILs and pCR with and without Cb based NACT. Methods: Patients diagnosed with TNBC and treated with NACT in University Hospital Galway, Ireland from 2004-2016 were identified. Patients were treated with a carboplatin-anthracycline-taxane regimen (Cb-AT) (n=30) or an AT regimen (n=54). As per the International TILs Working Group, sTILs were scored on digitized slides of full-face tumor sections from diagnostic needle core biopsies. sTILs were categorized as 0-10%; 11-25%; 26-49%; ≥50% (LPBC). Odds ratio (OR) was calculated using non-pCR as the baseline. pCR was defined as ypT0/isN0. Results: Eighty-eight (n=88) cases with sufficient sTILs for analysis were identified. The median sTIL count was 12.5% (range 0-75%): 50% of cases (n=44) had sTILs 0-10%; 25% (n=22) had sTILs 11-25%; 14% (n=12) had sTILs 26-49% and 11% (n=10) had sTILs ≥50%. Cases with sTILs &gt;10% had higher rates of pCR compared to those with sTILs ≤10% (52% vs 29%; p=0.021). In cases treated with an AT regimen, tumors with sTILs &gt;10% had higher pCR rates than those with sTILs ≤10% (46% vs 12%; p=0.005). In cases treated with a Cb-AT regimen, there was no difference in pCR rates between sTILs &gt;10% tumors and sTILs ≤10% tumors (60% vs 53%; p=0.500). In this cohort, pCR rates were higher in LPBC compared to non-LPBCs (80% vs 36%; p=0.010). In cases treated with AT, pCR rates were higher in LPBC than non-LPBC (83% vs 23%; p=0.007). However, in cases treated with Cb-AT, there were no differences in pCR rates between LPBC and non-LPBC (67% vs 56%; p=0.603). In LPBC, the choice of chemotherapy did not affect pCR rates: 67% vs 83% for Cb-AT and AT regimens respectively (p=0.583). In non-LPBC, pCR rates increased with Cb: 56% vs 23% for Cb-AT and AT regimens respectively (p=0.005). By univariate analysis, there was a significant association between sTILs and pCR. The association was greatest in LPBC (OR 0.14; p=0.016) and remained significant in those treated with AT (OR 0.06; p=0.014) but not in cases treated with Cb-AT (OR 0.63; p=0.714). In a multivariable model, with tumor grade and Cb use as co-variables, LPBC was independently associated with pCR (OR0.14; p=0.030). In cases treated with AT, sTILs were associated with pCR (OR 0.18, p=0.019 for sTILs &gt;10%; OR 0.08, p=0.029 for LPBC). In cases treated with Cb-AT, sTILs were not associated with pCR (p=0.372 and p=0.622 for sTILs &gt;10% and LPBC respectively). Conclusions: In TNBC, sTILs are predictive of response to NACT: as sTILs increase, pCR rates increase. The likelihood of a pCR increased by 86% for LPBC vs non-LPBC. The effect of sTILs on pCR was most notable in LPBC treated with AT based NACT where the odds of a pCR increased by 94%. In cases treated with Cb-AT, there was no association between sTILs and pCR. This study suggests that tumors with high sTILs are more chemosensitive than tumors with low sTILs. High sTIL tumors had high pCR rates with AT based NACT but the addition of Cb did not increase pCR rates. Cb-AT NACT could be reserved for patients with low sTIL tumors, in order to increase the rates of pCR in that subgroup, who had low rates of pCR in this study. In the future, sTILs could be used as a predictive biomarker to guide chemotherapy selection.
Citation Format: Elaine M Walsh, Mark O'Loughlin, Aliaa Shalaby, Mark Webber, Michael J Kerin, Sharon A Glynn, Grace Callagy, Maccon M Keane. Pathological complete response after carboplatin-based neoadjuvant chemotherapy in triple negative breast cancer: The importance of stromal tumor infiltrating lymphocytes as a predictive biomarker [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 P1-10-11.