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Prognostic Impact of High Baseline Stromal Tumor-Infiltrating Lymphocytes in the Absence of Pathologic Complete Response in Early-Stage Triple-Negative Breast Cancer

SIMPLE SUMMARY: High stromal tumor-infiltrating lymphocytes (sTILs) are associated with an improved pathologic complete response (pCR) and survival in triple-negative breast cancer (TNBC). We hypothesized that high baseline sTILs would have a favorable prognostic impact in TNBC patients without a pC...

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Detalles Bibliográficos
Autores principales: Abuhadra, Nour, Sun, Ryan, Litton, Jennifer K., Rauch, Gaiane M., Yam, Clinton, Chang, Jeffrey T., Seth, Sahil, Bassett, Roland, Lim, Bora, Thompson, Alastair M., Mittendorf, Elizabeth, Adrada, Beatriz E., Damodaran, Senthil, White, Jason, Ravenberg, Elizabeth, Candelaria, Rosalind, Arun, Banu, Ueno, Naoto T., Santiago, Lumarie, Saleem, Sadia, Abouharb, Sausan, Murthy, Rashmi K., Ibrahim, Nuhad, Sahin, Aysegul A., Valero, Vicente, Symmans, William Fraser, Tripathy, Debu, Moulder, Stacy, Huo, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909018/
https://www.ncbi.nlm.nih.gov/pubmed/35267631
http://dx.doi.org/10.3390/cancers14051323
Descripción
Sumario:SIMPLE SUMMARY: High stromal tumor-infiltrating lymphocytes (sTILs) are associated with an improved pathologic complete response (pCR) and survival in triple-negative breast cancer (TNBC). We hypothesized that high baseline sTILs would have a favorable prognostic impact in TNBC patients without a pCR. In this study of 318 early-stage TNBC patients in a prospective clinical trial, event-free survival (EFS) in patients without a pCR was not significantly different between those with high sTILs and those with low sTILs (p = 0.7). Therefore, high baseline sTILs do not confer a benefit in EFS in the absence of a pCR. RNA-seq analysis predicted more CD8+ T cells in the high-sTIL group with favorable EFS compared with the high-sTIL group with unfavorable EFS, suggesting the type of lymphocytes within the TIL fraction may be an important parameter to consider for de-escalation strategies. The implications of our findings in the setting of immune checkpoint inhibitor therapy remain to be investigated. ABSTRACT: High stromal tumor-infiltrating lymphocytes (sTILs) are associated with an improved pathologic complete response (pCR) and survival in triple-negative breast cancer (TNBC). We hypothesized that high baseline sTILs would have a favorable prognostic impact in TNBC patients without a pCR after neoadjuvant chemotherapy (NACT). In this prospective NACT study, pretreatment biopsies from 318 patients with early-stage TNBC were evaluated for sTILs. Recursive partitioning analysis (RPA) was applied to search for the sTIL cutoff best associated with a pCR. With ≥20% sTILs identified as the optimal cutoff, 33% patients had high sTILs (pCR rate 64%) and 67% had low sTILs (pCR rate 29%). Patients were stratified according to the sTIL cutoff (low vs. high) and response to NACT (pCR vs. residual disease (RD)). The primary endpoint was event-free survival (EFS), with hazard ratios calculated using the Cox proportional hazards regression model and the 3-year restricted mean survival time (RMST) as primary measures. Within the high-sTIL group, EFS was better in patients with a pCR compared with those with RD (HR 0.05; 95% CI 0.01–0.39; p = 0.004). The difference in the 3-year RMST for EFS between the two groups was 5.6 months (95% CI 2.3–8.8; p = 0.001). However, among patients with RD, EFS was not significantly different between those with high sTILs and those with low sTILs (p = 0.7). RNA-seq analysis predicted more CD8+ T cells in the high-sTIL group with favorable EFS compared with the high-sTIL group with unfavorable EFS. This study did not demonstrate that high baseline sTILs confer a benefit in EFS in the absence of a pCR.