Diffuse distribution of tumor-infiltrating lymphocytes is a marker for better prognosis and chemotherapeutic effect in triple-negative breast cancer

Hida, Akira I.; Watanabe, Takahiro; Sagara, Yasuaki; Kashiwaba, Masahiro; Sagara, Yoshiaki; Aogi, Kenjiro; Ohi, Yasuyo; Tanimoto, Akihide

doi:10.1007/s10549-019-05390-x

Cited by 40 publications

(37 citation statements)

References 44 publications

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“…Further, there is some evidence that the spatial distribution of TILs may provide additional prognostic information 42 . One study reported improved prognosis and response to chemotherapy in TNBC with a diffuse, homogeneous lymphocyte distribution versus a heterogeneous distribution 43 . This requires further evaluation.…”

Section: Frequency Seen Recommendationmentioning

confidence: 99%

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Kos¹,

et al. 2020

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Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls.

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Section: Frequency Seen Recommendationmentioning

confidence: 99%

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Kos¹,

et al. 2020

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“…These remarks are true for all cancer types as much as for TNBCs [6,7]. High tumor infiltrating lymphocytes (TILs) density has been associated to a better prognosis also in TNBCs and to an enhanced pathological complete response [8]. Now seems clear that high TILs presence makes a more favorable tumor microenvironment, affecting tumor progression also in an adverse subset of tumors such as TNBCs [9].…”

Section: Introductionmentioning

confidence: 99%

Should Tumor Infiltrating Lymphocytes, Androgen Receptor, and FOXA1 Expression Predict the Clinical Outcome in Triple Negative Breast Cancer Patients?

Mangia

Saponaro

Vagheggini

et al. 2019

Cancers

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Tumor-infiltrating lymphocytes (TILs) are a valuable indicator of the immune microenvironment that plays the central role in new anticancer drugs. TILs have a strong prognostic role in triple negative breast cancer (TNBC). Little is known about the interaction with the androgen receptor (AR) and forkhead box A1 (FOXA1). We analyzed the relationships between TIL levels, AR, and FOXA1 expression and their clinical significance in TNBC patients. Further, we investigated their interaction with other biomarkers like programmed cell death ligand-1 (PD-L1), breast cancer type 1 susceptibility protein (BRCA1), poly (ADP-Ribose) polymerase 1 (PARP1), and Na+/H+ exchanger regulatory factor 1 (NHERF1). The expression of the proteins was evaluated by immunohistochemistry in 124 TNBC samples. TILs were performed adhering to International TILs Working Group 2014 criteria. Cox proportional hazards models were also used to identify risk factors associated with poor prognosis. Multivariate analysis identified TILs as independent prognostic factor of disease free survival (DFS; p = 0.045). A Kaplan–Meyer analysis revealed that the patients with high TILs had a better DFS compared to patients with low TILs (p = 0.037), and the phenotypes TILs−/AR+ and TILs−/FOXA1− had a worse DFS (p = 0.032, p = 0.001 respectively). AR was associated with FOXA1 expression (p = 0.007), and the tumors FOXA1+ presented low levels of TILs (p = 0.028). A poor DFS was observed for AR+/FOXA1+ tumors compared to other TNBCs (p = 0.0117). Low TILs score was associated with poor patients’ survival, and TILs level in combination with AR or FOXA1 expression affected patient’s clinical outcome. In addition, AR+/FOXA1+ phenotype identified a specific subgroup of TNBC patients with poor prognosis. These data may suggest new ways of therapeutic intervention to support current treatments.

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“…Elevated TIL scores were proven to correlate with increased pathological complete response to neoadjuvant chemotherapy. [44][45][46][47] This proves that the immune system plays a pivotal role in this subgroup of patients.…”

Section: Checkpoint Inhibition In Triple-negative Breast Cancermentioning

confidence: 72%

<p>Immunotherapy for the Treatment of Breast Cancer: Emerging New Data</p>

Mina

Lim

Bahadur

et al. 2020

BCTT

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Breast cancer is the most common type of cancer affecting women in the United States. Triple-negative breast cancer remains the most aggressive molecular subtype secondary to a lack of therapeutic targets. The search for a target has led us to investigate immunotherapeutic agents. Immunotherapy has recently demonstrated significant breakthroughs in various types of cancers that are refractory to traditional therapies including melanoma and Non-Small Cell Lung Cancer (NSCLC). Breast cancer however remains one of the tumors that was initially least investigated because of being considered to have a low immunogenic potential and a low mutational load. Over the past few years, antiPD1/PDL1 drugs have started to make progress in the triple-negative subtype with more promising outcomes. In this report, we review the treatment of triple-negative breast cancer and specifically shed light on advances in immunotherapy and newly approved drugs in this challenging disease.

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Diffuse distribution of tumor-infiltrating lymphocytes is a marker for better prognosis and chemotherapeutic effect in triple-negative breast cancer

Cited by 40 publications

References 44 publications

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

Should Tumor Infiltrating Lymphocytes, Androgen Receptor, and FOXA1 Expression Predict the Clinical Outcome in Triple Negative Breast Cancer Patients?

<p>Immunotherapy for the Treatment of Breast Cancer: Emerging New Data</p>

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