Facts and Hopes in Immunotherapy for Early-Stage Triple-Negative Breast Cancer

Abstract

A substantial fraction of early-stage triple-negative breast cancer (eTNBC) is characterized by high levels of stromal tumor-infiltrating lymphocytes (sTILs) and has a good prognosis even without systemic treatment, highlighting the importance of an endogenous anti-cancer immune response. Still, a considerable proportion of patients with eTNBC needs some ‘therapeutical push’ to kick-start this immune response. Exploiting this immune response with immune checkpoint inhibition (ICI), in combination with chemotherapy, has made its way into standard-of-care in eTNBC. Major challenges in the near future include finding those patients with eTNBC that can be treated with ICI alone or with a reduced chemotherapy backbone. Exploring the optimal duration of ICI and finding biomarkers to predict response will be key to enable personalized implementation of ICI in patients with eTNBC. For patients that currently do not respond effectively to ICI plus chemotherapy, challenges lie in finding new immunomodulatory therapies and develop response-guided neoadjuvant approaches.

Knowledge mapping of immunotherapy for breast cancer: A bibliometric analysis from 2013 to 2022

“…Sherene Loi was identified as the author with the highest citation count (4007), total link strength (686), and H-index, 29 while Giuseppe Curigliano had the highest number of publications 30 and G-index. 31 Table 4 presents the top 10 publishing institutions, with The University of Texas MD Anderson Cancer Center having the highest number of publications (219), Harvard Medical School receiving the highest number of citations (14490), and Dana-Farber Cancer Institute having the highest average citation count per publication (112.86). The collaboration relationships among institutions are divided into eight clusters, as shown in Figure 4(d) .…”

“… 52 In studies such as IMpassion-031 and KEYNOTE-522, PD-L1-positive tumor patients were associated with higher pCR rates. 31 Further analysis of the GeparNuevo study revealed TMB and immune infiltration as independent predictors of response to neoadjuvant immune checkpoint inhibition in early triple-negative breast cancer. 53 Continued development of rational and precise immunotherapy biomarkers is crucial for accurately selecting breast cancer patients who will benefit from immunotherapy.…”

KLF2 is a clinical diagnostic and treatment biomarker of breast cancer

“…Previous reports have highlighted the important role of KLF2 in regulating the tumor immune microenvironment ( Rabacal et al, 2016 ; Tang et al, 2017 ; Osman et al, 2021 ; Qu et al, 2022 ), while immunotherapy represents a significant hope for breast cancer treatment ( Emens, 2018 ; Nederlof et al, 2023 ). Therefore, we analyzed the relationship between KLF2 and tumor immune infiltration in the TIMER database, and found that it was highly correlated with the expression of most immune marker proteins, and the most significant is correlated with dendritic cell immune marker genes, including CD1C, THBD and NRP1.…”

Cancer cell‐derived exosomal miR‐20a‐5p inhibits CD8+ T‐cell function and confers anti‐programmed cell death 1 therapy resistance in triple‐negative breast cancer

“…Chemotherapy has been considered as the only viable systemic treatment option for TNBC. However, recent studies showed that TNBC is more likely to benefit from immunotherapy due to its rich infiltration of lymphocytes and higher immunogenicity 6–9 . Thus far, treatment of anti‐programmed cell death 1 (PD‐1) monoclonal antibody combined with chemotherapy has shown an impressive pathological complete rate in patients with TNBC 10–12 .…”

“…However, recent studies showed that TNBC is more likely to benefit from immunotherapy due to its rich infiltration of lymphocytes and higher immunogenicity. 6 , 7 , 8 , 9 Thus far, treatment of anti‐programmed cell death 1 (PD‐1) monoclonal antibody combined with chemotherapy has shown an impressive pathological complete rate in patients with TNBC. 10 , 11 , 12 Unfortunately, based on the clinical experience of PD‐1 therapy in other cancers, a major of patients inevitably acquire therapy resistance after a period of treatment.…”