Comparisons of tumor-infiltrating lymphocyte levels and the 21-gene recurrence score in ER-positive/HER2-negative breast cancer

Ahn, Sung Gwe; Jin, Yoon; Bae, Soong June; Yoon, Choon Sik; Lee, Hak Woo; Lee, Jeong Eon

doi:10.1186/s12885-018-4228-6

Cited by 25 publications

(22 citation statements)

References 34 publications

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“…The TIL score was evaluated as previously described [ 20 , 21 ]. A pathologist (YJC) blinded to the clinical information reviewed the histologic features using hematoxylin and eosin (H&E) staining.…”

Section: Methodsmentioning

confidence: 99%

Associations between absolute neutrophil count and lymphocyte-predominant breast cancer

et al. 2020

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Introduction Tumor-infiltrating lymphocytes (TILs) might be associated with host-cell mediated immunity, which could be partly reflected by peripheral blood cell counts. In addition, lymphocyte-predominant breast cancer (LPBC), which was defined as tumors having high TIL levels, showed a favorable prognosis among triple-negative breast cancer or HER2-positive breast cancer. We aimed to investigate whether peripheral blood cell counts are associated with LPBC. Methods We evaluated the percentage of stromal TILs in breast cancer patients who underwent primary surgery, using the standardized methodology proposed by the international TIL Working Group. Lymphocyte-predominant breast cancer (LPBC) was defined as tumors having high TIL levels (≥50%). Peripheral blood cell counts including absolute neutrophil counts (ANC), absolute lymphocyte counts (ALC) and neutrophil-to-lymphocyte ratio (NLR) was obtained from pretreatment laboratory data. Result Of the 810 patients, 132 (16.3%) had LPBC, and 678 (83.7%) had non-LBPC. In a comparison of 3 markers of peripheral blood counts, LPBC had a significantly lower mean ANC than non-LPBC (3,304 vs. 3,564; P = 0.023), but the other means were not different. In multivariable analysis, each 1K increment in ANC corresponded to an odds ratio of 0.790 (95% CI, 0.642 to 0.971) for LPBC. In the ER-negative and high-Ki67 subgroups identified by interaction tests, significant inverse correlations between continuous ANC and TILs were noted. Conclusion Low peripheral ANC could be linked with LPBC, supporting the hypothesis that systemic immune cell counts might be associated with the tumor-immune microenvironment.

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Section: Methodsmentioning

confidence: 99%

Associations between absolute neutrophil count and lymphocyte-predominant breast cancer

et al. 2020

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“…TNBC was defined by the lack of ER, PR and HER2 based on immunohistochemical (IHC) stain. For routine IHC studies, ER (1:100 clone 6F11; Novocastra, Newcastle upon Tyne, UK), PR (clone 16; Novocastra), HER2 (4B5 rabbit monoclonal antibody; Ventana Medical Systems, Tucson, AZ, USA), and Ki-67 (MIB-1; Dako, Glostrup, Denmark) were stained using formalin-fixed paraffin-embedded tissue sections as previously described [13,14]. ER positivity and PR expression on immunohistochemistry were defined according to the modified Allred system.…”

Section: Patients and Tumor Samplesmentioning

confidence: 99%

Clinical and genomic assessment of PD-L1 SP142 expression in triple-negative breast cancer

Ahn

Kim

Shepherd

et al. 2021

Breast Cancer Res Treat

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Purpose The SP142 PD-L1 assay is a companion diagnostic for atezolizumab in metastatic triple-negative breast cancer (TNBC). We strove to understand the biological, genomic, and clinical characteristics associated with SP142 PD-L1 positivity in TNBC patients. Methods Using 149 TNBC formalin-fixed paraffin-embedded tumor samples, tissue microarray (TMA) and gene expression microarrays were performed in parallel. The VENTANA SP142 assay was used to identify PD-L1 expression from TMA slides. We next generated a gene signature reflective of SP142 status and evaluated signature distribution according to TNBCtype and PAM50 subtypes. A SP142 gene expression signature was identified and was biologically and clinically evaluated on the TNBCs of TCGA, other cohorts, and on other malignancies treated with immune checkpoint inhibitors (ICI). Results Using SP142, 28.9% of samples were PD-L1 protein positive. The SP142 PD-L1-positive TNBC had higher CD8+ T cell percentage, stromal tumor-infiltrating lymphocyte levels, and higher rate of the immunomodulatory TNBCtype compared to PD-L1-negative samples. The recurrence-free survival was prolonged in PD-L1-positive TNBC. The SP142-guided gene expression signature consisted of 94 immune-related genes. The SP142 signature was associated with a higher pathologic complete response rate and better survival in multiple TNBC cohorts. In the TNBC of TCGA, this signature was correlated with lymphocyte-infiltrating signature scores, but not with tumor mutational burden or total neoantigen count. In other malignancies treated with ICIs, the SP142 genomic signature was associated with improved response and survival. Conclusions We provide multi-faceted evidence that SP142 PDL1-positive TNBC have immuno-genomic features characterized as highly lymphocyte-infiltrated and a relatively favorable survival.

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“…Although the RT-PCR results have been shown to be highly concordant with the results of IHC/fluorescent in situ hybridization (FISH) assays [ 26 , 27 ], the potential variability in RS values between CNBs and resection specimens is multifactorial and can be affected by single-gene expression, tumour heterogeneity and pre-analytic differences such as the delay to fixation, duration of fixation, or differences in fixatives. Furthermore, it has been reported that the presence of increased stromal cellularity and/or associated inflammatory cells and tumour-infiltrating lymphocytes (TILs) may contribute to an apparently increased recurrence risk according to the 21-gene assay [ 28 , 29 ]. Consequently, in this study, we assessed the ER, PR, HER-2 and Ki-67 status and RS value in paired CNBs and resection specimens from 50 BC patients.…”

Section: Introductionmentioning

confidence: 99%

Concordance of the 21-gene assay between core needle biopsy and resection specimens in early breast cancer patients

Pan

Bai

et al. 2021

Breast Cancer Res Treat

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Background Adjuvant therapy decisions may be partly based on the results of a multigene quantitative reverse transcription-polymerase chain reaction (RT-PCR)-based assay: the 21-gene recurrence score (RS) test of resection specimens. When necessary, core needle biopsy (CNB) may be considered as a surrogate. Here, we evaluated the concordance in gene expression according to results from RT-PCR-based RS testing between paired CNBs and resection specimens. Methods CNBs and resection specimens from 50 breast cancer (BC) patients were tested to calculate RSs. First, we examined the concordance of the ER, PR and HER-2 status of tissue samples indicated by immunohistochemical (IHC) and RT-PCR analyses. Then, we compared the IHC findings of ER, PR, HER-2 and Ki-67 staining across paired samples. Ultimately, the RS and single-gene results for ER, PR, HER-2 and Ki-67 were explored between paired samples. Results The concordance between IHC and RT-PCR was 100%, 80.0% and 100% for ER, PR and HER-2, respectively, in both resection specimens and CNBs. The concordance for IHC ER, PR, HER-2 and Ki-67 status was 100%, 94.0%, 52.0% and 82.0%, respectively, between paired samples. RS results from paired samples showed a strong correlation. The overall concordance in RS group classification between samples was 74%, 72% and 78% based on traditional cutoffs, TAILORx cutoffs and ASCO guidelines, respectively. ER, PR, HER-2 and Ki-67 were modestly- to- strongly correlated between paired samples according to the RT-PCR results. Conclusion A modest- to- strong correlation of ER, PR, HER-2 and Ki-67 gene expression and RS between CNBs and resection specimens was observed in the present study. The 21-gene RS test could be reliably performed on CNBs. ER, PR and HER-2 status showed remarkable concordance between the IHC and RT-PCR analyses. The concordance between paired samples was high for the IHC ER, PR and Ki-67 results and low for HER-2.

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Comparisons of tumor-infiltrating lymphocyte levels and the 21-gene recurrence score in ER-positive/HER2-negative breast cancer

Cited by 25 publications

References 34 publications

Associations between absolute neutrophil count and lymphocyte-predominant breast cancer

Associations between absolute neutrophil count and lymphocyte-predominant breast cancer

Clinical and genomic assessment of PD-L1 SP142 expression in triple-negative breast cancer

Concordance of the 21-gene assay between core needle biopsy and resection specimens in early breast cancer patients

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