Triple-negative breast cancer (TNBC) occurs more frequently in young (<50 years) non-Hispanic black and Hispanic/Latina women. It is considered the most aggressive subtype of breast cancer, although, recently, immune infiltrate has been associated with long-term survival, lower risk of death and recurrence, and response to neoadjuvant chemotherapy. The aim of this review was to evaluate the clinical impact of the immune infiltrate in TNBC by discussing whether its prognostic value varies across different populations. A comprehensive systematic search in databases such as PubMed and Web of Science was conducted to include papers focused on tumor-infiltrating lymphocytes (TILs) in TNBC in different population groups and that were published before January 2021. TNBC patients with higher levels of TILs had longer overall survival and disease-free survival times compared with TNBC patients with low TIL levels. Similar results were observed for CD4+, CD8+ TIL populations. On the other hand, patients with high TIL levels showed a higher rate of pathological complete response regardless of the population group (Asian, European, and American). These results altogether suggest that TIL subpopulations might have a prognostic role in TNBC, but the underlying mechanism needs to be elucidated. Although the prognosis value of TILs was not found different between the population groups analyzed in the revised literature, further studies including underrepresented populations with different genetic ancestries are still necessary to conclude in this regard.
Introduction: Triple negative breast cancer (TNBC), occurs in 10%-20% of all breast cancer and presents a higher frequency in Latinas compared to non-Hispanic white women. It is highly immunogenic and high levels of tumor infiltrating lymphocytes (TILs) have been associated with a better overall survival and higher probability to achieve pathological complete response (pCR). Objective: This is the first study in Colombian women aimed to explore stromal TILs (sTILs) level and composition as a prognostic and predictive biomarker in TNBC. Methods: A total of 195 TNBC tumor biospecimens from patients diagnosed between 2008-2016 in 3 Colombian health institutions were included. Stromal TILs (sTILs) was evaluated following the recommendations of the International TILs Working Group 2014 in hematoxylin & eosin slides from pre-treatment samples. The number of positive cells for CD4 and CD8 was evaluated by immunohistochemistry and digital image capture. Parametric and non-parametric tests were used to evaluate differences in clinic-pathological characteristics according to sTILs levels and composition. Differences in overall survival were analyzed using Kaplan-Meier curves and the log-rank test. Cox regression analysis was used to analyze sTILs as a prognostic marker for overall survival. A logistic regression model was applied to evaluate the association of sTILs with pCR. Results: Tumors with high sTILs levels were more likely to be early stage (64.4% stage I/II) compared to tumors with low sTILs levels (35.5%). Additionally, when compared patients with high sTILs vs. low sTILs, a higher percentage of patients with high sTILs didn’t receive neoadjuvant chemotherapy (NAC) (high:50% vs. low:32.7%, p=0.025) and received more conservative surgeries (high:60% vs. low:37.9%, p<0.05). Similar results were observed for patients with high CD4/8 infiltration. Longer overall survival times were observed in patients with high sTILs (84.9 mo vs. 41.4 mo, p<0.05), as well as in patients with high CD4+ infiltration (p<0.05) and CD8+ (p<0.015). In the multivariate analysis, low levels of sTILs was found to be independent prognostic factor associated with a higher risk of death (HR: 1.59, 95% CI 1.01-2.48). Regarding sTILs as a predictive biomarker, a higher number of patients with high sTILs and high CD4+ cells achieved clinical complete response to NAC (sTILs: 28.6% vs. 9.3%, p=0.022; CD4: 29% vs 9.4%, p=0.032) and pCR (sTILs: 42.9% vs. 15.8%, p=0.023; for CD4: 43.3% vs 16.3%, p=0.006) compared to patients with low infiltration. Likewise, a statistically significant association between sTILs and pCR was observed (OR: High sTILs 1.486, 95% CI 1.14 - 2.013). Similar results were observed for high CD4 and CD8 infiltration (OR: 1.262, 95% CI 1.061 - 1.536, OR: 1.337, 1.085 - 1.694, respectively). Conclusions: Our results suggest that sTILs levels are a prognostic marker for overall survival and a predictive marker for pCR in TNBC patients from Colombia as has been reported in previous studies including biospecimens from mostly European ancestry patients. Citation Format: Carlos A. Huertas-Caro, Mayra A. Ramirez, Diego Felipe Ballen, Juan Carlos Mejía, Luz Fernanda Sua-Villegas, Alicia Cock-Rada, Jovanny Zabaleta, Laura Fejerman, María Carolina Sanabria-Salas, Silvia J. Serrano-Gomez. Tumoral infiltrating lymphocytes as a prognostic factor in triple negative breast cancer patients from Colombia [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR007.
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