Association of pathological complete response rates and TILs in triple-negative breast cancer patients.
Authors: Kassem Mahmoud , Goldstein Daniel , Schnell Patrick , Grimm Michael , Quiroga Dionisia Marie , Miah Abdul , Vargo Craig , Shinde Namrata Vilas , Michael Berger , Pariser Ashley , Gatti-Mays Margaret Elena , VanDeusen Jeffrey Bryan , Williams Nicole Olivia , Stover Daniel G. , Sardesai Sagar D. , Wesolowski Robert , Lustberg Maryam B. , Ramaswamy Bhuvaneswari , Tozbikian Gary , Cherian Mathew Amprayil 
Published: June 2021

e12596

Background: Triple negative breast cancers (TNBC), characterized by the lack of expression of estrogen receptors and progesterone receptors as well as human epidermal growth factor receptor 2, are associated with high distant recurrence rate and death. As a result, the majority of patients with TNBC are treated with perioperative chemotherapy with the goal of eradicating micrometastases and preventing distrant relapse. The preoperative systemic therapy offers the advantages of permitting an assessment of chemo-sensitivity, increased rates of breast conserving surgery and the ability to adapt postoperative therapies depending on the response. Recently, neoadjuvant chemotherapy has been used at an increasing frequency. The response to neoadjuvant chemotherapy, as measured by the residual cancer burden index, for example, is correlated with the long-term prognosis of TNBC and HER2 expressing breast cancers. Previous studies suggest that tumor-infiltrating lymphocytes (TILs) may correlate with pathological complete response (pCR) rates in TNBC patients treated with neoadjuvant chemotherapy. The pathologic evaluation of TILs in TNBC has been recommended by the International TILs working group since 2014. In this study we sought to analyze the association of TILs with pCR in a cohort of TNBC patients treated with neoadjuvant chemotherapy. Methods: An IRB-approved single-institution retrospective analysis was performed on 127 patients diagnosed with TNBC who received neoadjuvant anthracycline and taxane based chemotherapy at the Ohio State University Comprehensive Cancer Center between January 1st, 2012 and November 31st, 2018. We analyzed TILs as a continuous variable as a part of a secondary analysis of this data. Whole tissue sections from archived H&E stained glass slides were scanned using Philips UltraFast Scanner at ×40 magnification with a single-focus layer. TIL scoring was performed according to guideline recommendations from the International TILs Working Group (2014). Results: A total of 127 female patients with TNBC were identified. The median age at diagnosis was 52.0 years (range 32.0, 74.0) and patients were predominately white (103, 81%), post-menopausal (68, 53.5%) and presented with invasive ductal cancer (113, 89%), stage II (88, 69%), and high grade (108, 85%). Of those patients, 56 had TILs measurement available. pCR was associated with statistically higher level of TILs in core biopsies taken prior to chemotherapy had (Wilcoxon rank-sum test, p = 0.04). Conclusions: The long-term prognosis of patients with TNBC is predicted by the response to neoadjuvant chemotherapy. Consistent with other studies, our study revealed that TILs are associated with a higher probability of pCR. Our future goals are to identify which TIL subsets correlate best with pCR and to identify the mechanism for the increased chemotherapy responsiveness of lymphocyte-infiltrated tumors.