Tumor-infiltrating lymphocytes are important pathologic predictors for neoadjuvant chemotherapy in patients with breast cancer

Yamaguchi, Rin; Tanaka, Maki; Yano, Ayako; Tse, Gary M.; Miki, Yoshio; Koura, Keiko; Kanomata, Naoki; Kawaguchi, Atsushı; Akiba, Jun; Naito, Yoshiki; Ohshima, Koichi; Yano, Hirohisa

doi:10.1016/j.humpath.2011.12.013

Cited by 128 publications

(88 citation statements)

References 23 publications

(47 reference statements)

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“…Tables 1 and 2 show the abstracted data of the included studies. Eighteen studies evaluated the prognostic utility of LIs on RFS and/or OS [13,[21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37], and 5 studies examined the value of LIs in predicting pCR [21,34,[38][39][40] (two of those 5 studies also examined survival [21,34].…”

Section: Resultsmentioning

confidence: 99%

The Prognostic and Predicting Roles of Tumor-Infiltrating Lymphocytes in Breast Cancer: A Meta-Analysis

Ibrahim¹,

Al‐Foheidi²,

Al‐Μansour³

et al. 2014

TOBCANJ

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Section: Resultsmentioning

confidence: 99%

The Prognostic and Predicting Roles of Tumor-Infiltrating Lymphocytes in Breast Cancer: A Meta-Analysis

Ibrahim¹,

Al‐Foheidi²,

Al‐Μansour³

et al. 2014

TOBCANJ

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“…In addition, some investigators have reported that immunologic parameters are relevant for response to NAC in breast cancer [13][14][15][16] as well as for outcomes after adjuvant chemotherapy [17][18][19]. The predictive significance of TILs was proven by histological evaluation by hematoxylin and eosin (H&E) and immunohistochemical staining [14,16]. Furthermore, Denkert et al showed at the molecular level that the expression of T cell-related markers CD3D and CXCL9 was significantly associated with a pCR [13].…”

Section: Introductionmentioning

confidence: 99%

Prognostic and predictive value of NanoString-based immune-related gene signatures in a neoadjuvant setting of triple-negative breast cancer: relationship to tumor-infiltrating lymphocytes

Lee

Song

et al. 2015

Breast Cancer Res Treat

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The prognostic significance of tumor-infiltrating lymphocytes and immune signals has been described previously in triple-negative breast cancer (TNBC). Furthermore, recent studies have shown that immunologic parameters are relevant for the response to neoadjuvant chemotherapy (NAC) in breast cancer as well as for outcomes after adjuvant chemotherapy. However, immune signals are variable, and which signals are important is largely unknown. We, therefore, evaluated the expression of immune-related genes in TNBC treated with NAC. We retrospectively evaluated biopsy tissue from 55 patients with primary TNBC treated with NAC (anthracycline, cyclophosphamide, and docetaxel) against the NanoString nCounter GX Human Immunology Panel (579 immune-related genes). Higher expression of cytotoxic molecules, T cell receptor signaling pathway components, cytokines related to T helper cell type 1 (Th1), and B cell markers was associated with a pathologic complete response (pCR). Higher expression of NFKB1, MAPK1, TRAF1, CXCL13, GZMK, and IL7R was significantly associated with pCR, higher Miller-Payne grade, and lower residual cancer burden class. Expression of NFKB1, TRAF1, and CXCL13genes, in particular, was significantly correlated with a longer disease-free survival rate. Conversely, patients those who failed to achieve a pCR showed increased expression of genes related to neutrophils. Higher expression of cytotoxic molecules, T cell receptor signaling pathway components, Th1-related cytokines, and B cell markers is correlated with pCR and survival in TNBC patients treated with NAC. Our results suggest that the activation status of neutrophils may provide additional predictive information for TNBC patients treated with NAC.

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“…Furthermore, the presence of TILs in pretreated TNBC and HER2-positive breast cancers is associated with improved overall and disease-free survival [8]. Additionally, high amounts of TILs are associated with pathological complete response (pCR) after neoadjuvant chemotherapy (NACT), regardless of the intrinsic breast cancer subtype [9][10][11]. In order to further facilitate this immunogenic potential and to minimize the systemic burdens of chemotherapies, targeted immunotherapies have been the focus of current research programs [12].…”

Section: Introductionmentioning

confidence: 99%

TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients - First Results on the Influence of Tumor-Infiltrating Lymphocytes

et al. 2018

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Background: Despite advancements in the treatment of primary and metastatic breast cancer, many patients lack a durable response to these treatments. Patients with triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2(HER2)-positive breast cancer who do not have a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) have a very poor prognosis. Tumor-infiltrating lymphocytes (TILs) have been identified as a predictive marker for pCR after NACT in TNBC and HER2-positive breast cancer. These patient populations could also be suitable for novel treatment strategies including neoepitope-based therapies. This work analyses the effect of TILs on the pCR in neoadjuvantly treated patients in the TILGen study and presents the procedures aimed at establishing neoepitope-based therapies in this study. Methods: Neoadjuvantly treated HER2-positive and TNBC patients were eligible for the presented analysis concerning the association between TILs and pCR. A total of 146 patients could be identified within the TILGen study. TILs were evaluated as percentage of stromal tumor tissue in core biopsies at primary diagnosis. The phenotype ‘lymphocyte-predominant breast cancer' (LPBC) was associated with pCR by logistic regression adjusted for estrogen receptor status, progesterone receptor status, HER2 status, age at diagnosis, and grading. Results: LPBC was seen in 24 (16.4%) patients. In this patient group, 66.7% achieved a pCR, while the pCR rate was 32.8% in patients with a low TIL count. The adjusted odds ratio was 6.60 (95% confidence interval 2.02-21.56; p < 0.01). Conclusion: TILs are a strong predictor of pCR in TNBC and HER2-positive breast cancer patients. Implications for the use of this information including the effect on prognosis might help to identify patients most likely to benefit from a neoepitope-based therapy approach.

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Tumor-infiltrating lymphocytes are important pathologic predictors for neoadjuvant chemotherapy in patients with breast cancer

Cited by 128 publications

References 23 publications

The Prognostic and Predicting Roles of Tumor-Infiltrating Lymphocytes in Breast Cancer: A Meta-Analysis

The Prognostic and Predicting Roles of Tumor-Infiltrating Lymphocytes in Breast Cancer: A Meta-Analysis

Prognostic and predictive value of NanoString-based immune-related gene signatures in a neoadjuvant setting of triple-negative breast cancer: relationship to tumor-infiltrating lymphocytes

TILGen: A Program to Investigate Immune Targets in Breast Cancer Patients - First Results on the Influence of Tumor-Infiltrating Lymphocytes

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