Prognostic Value of Tumor-Infiltrating Lymphocyte Density Assessed Using a Standardized Method Based on Molecular Subtypes and Adjuvant Chemotherapy in Invasive Breast Cancer

Jang, Nuri; Kwon, Hee Jung; Park, Min Hui; Kang, Su Hwan; Bae, Young Kyung

doi:10.1245/s10434-017-6332-2

Cited by 46 publications

(38 citation statements)

References 27 publications

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“…Numerous studies have recently quantified immune cell infiltrations in and around tumors. Most of these have used semi-quantitative methods to describe their data such as cell counts per highpower field or per predefined tissue area, positive pixel counts per area, semi-quantitative estimation of TIL numbers or the fraction of TILs in relation to the total intra-tumoral stroma [20][21][22][23][24][25][26]. Data on lymphocytic infiltration in cancers cannot always easily be compared between studies because objective metric data are often lacking.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of CD8+ cytotoxic lymphocytes in human neoplasms

Blessin

Spriestersbach

et al. 2020

Cell Oncol.

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Purpose Immune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that the quantity of tumor infiltrating lymphocytes (TILs) influences the likelihood of response to immune checkpoint inhibitors. Here, we set out to assess the density of CD8 + lymphocytes in a wide range of different cancer types and subtypes. Methods The density of CD8 + lymphocytes was compared across different cancer types using tissue microarrays (TMAs) composed of up to 50 tumor samples each from 84 different cancer types and subtypes. In total 2652 cancers and 608 normal tissues were successfully analyzed by CD8 immunohistochemistry followed by automated image analysis of digitized slides. Results We found that the median CD8 + lymphocyte counts ranged from 6 cells/mm 2 in pleomorphic adenoma up to 1573 cells/ mm 2 in Hodgkin's lymphoma. The CD8 counts were generally lower in normal tissues compared to cancer tissues. Blood vessels of the spleen were the only non-lymphatic tissue staining positive for CD8. Tumor types approved for checkpoint inhibitor therapy, including malignant melanoma (81), muscle invasive urothelial carcinoma (119), small cell lung cancer (120), clear cell renal cell cancer (153), squamous cell carcinoma (189) and adenocarcinoma of the lung (328) as well as Hodgkin's lymphoma (1573) were all ranking among the upper half of our list. Comparably high CD8 densities (median cells/mm 2) were also found in several rare and aggressive cancer types including Merkel cell carcinoma (70), angiosarcoma (95), anaplastic thyroid cancer (156) and embryonal carcinoma of the testis (186). In 73 of the 84 analyzed cancer types, the highly variable CD8 counts occasionally exceeded the average CD8 count of tumors for which checkpoint inhibitors have been approved. Conclusion These data support the concept that among most tumor types at least some individual cancers may benefit from treatment with immune checkpoint inhibitors.

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Section: Discussionmentioning

confidence: 99%

Prevalence of CD8+ cytotoxic lymphocytes in human neoplasms

Blessin

Spriestersbach

et al. 2020

Cell Oncol.

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“…In our study, the cut off between TILs high and low groups was 30%, this value allowed for a significant correlation between TILs and different prognostic indicators. Other reports employed different cut off points for this purpose such as 35% cut off in a study by Kotoula et al, in 2016, while Jang and colleagues reported 10% cut off value to define TILs levels that were associated with better outcomes for a subset of hormone positive breast cancer patients [24] [25]. [26].…”

Section: Discussionmentioning

confidence: 99%

Prediction of Response to Neoadjuvant Chemotherapy in Egyptian Patients with Locally Advanced Breast Cancer: The Evolving Role of Tumour Infiltrating Lymphocytes (TILs)

El-Mahdy¹,

Ibrahim²,

Hamed³

et al. 2020

JCT

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Background & objectives: Presence of TILs in breast cancer indicates better therapeutic responses to neoadjuvant chemotherapy (NAC), increased pCR and improved outcome. We aim at evaluation of TILs in breast cancer biopsies in correlation with pathological response after NAC in locally advanced breast cancer Methods. This study was conducted at Ain Shams university hospital and Maadi Military hospital in Egypt. 45 Female patients with locally advanced breast cancer were treated with NAC; pathological response was assessed. Tumours were categorized into: luminal A, luminal B, Her2 enriched and TNBC. Assessment of TILs (CD4 and CD8 lymphocytes) was based on Immuno-Oncology Biomarker Working Group guidelines. Results: Tumours were classified into high and low TIL groups using the interquartile range cutoff (29%). High CD4 group showed increased pCR (p = 0.003) and smaller residual tumours (p = 0.04). High CD8 group showed a significant association with smaller residual tumours (p = 0.003). At follow-up of 24-months, CD4 and CD8 high groups showed significantly higher 2-years DFS. The difference between CD4 high and low groups was significant in regards to estrogen receptor status, showing higher levels in hormone-negative tumors (p = 0.029). Patients with Her2 subtype showed higher CD4 (p = 0.007) and CD8 expression (p = 0.018). In CD4 & CD8 low groups, more patients developed local recurrence and distant metastasis (p = 0.025). Conclusion: We concluded that TILs may predict response to NAC and overall prognosis of breast cancer. The evaluation of TILs in correlation with mor-How to cite this paper: El-Mahdy, M.M., Ibrahim, R.A., Hamed, R.M., Elkady, M.S., Bayoumy, W.A., Elsayed, Z.M. and Ezz-El-Din, M.M. (2020)

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“…In addition to the tumor subtype, younger age, black race, unmarried status, uninsured status, and higher pathological grade are relevant factors for the developing of BCSHM in this study and were described earlier as relevant factors for advanced disease 17 - 21 . Some studies also describe possible genetic changes as relevant factors for distant metastasis of BCs 22 . Unfortunately, data on genetics and Ki-67% are not yet available in our study 18 .…”

Section: Discussionmentioning

confidence: 99%

Incidence and Survival Outcomes of Breast Cancer with Synchronous Hepatic Metastases: A Population-Based Study

Xiao¹,

Zheng²,

Yang³

et al. 2018

J. Cancer

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Background: Little is known about the clinical features of breast cancer with synchronous hepatic metastases (BCSHM). In this retrospective study, we aimed to feature the incidence and survival outcome of BCSHM.Methods: Data from the 2016 SEER*Stat database (version 8.3.2) was used. The effect of patient and tumor characteristics on the odds of developing of BCSHM was analyzed. Survival was investigated using Kaplan-Meier and Cox regression analyses. A competing risk model was also applied to further investigate cancer-specific survival.Results: Of 240911 patients with breast cancer, we identified 3468 patients (1.44%) with BCSHM. Tumor subtypes distribution of BCSHM were 45.3% HR+/HER2-, 12.2% HR+/HER2+, 7.83% HR-/HER2+ and 15.0% triple-negative subtype. The median OS of the entire cohort was 14 months, and only about 13.5% of patients survived at 3 years. Median survival was significantly shorter in triple-negative cohort (8 months) and gradually increased in HR+/HER2- (19 months), HR-/HER2+ (22 months) and HR+/HER2+ (33 months) cohorts (P<0.05). Patients BCSHM were more likely to be young age (odds ratio [OR] 1.4, 95% CI 1.0-2.0), black race (OR 1.13, 95%CI 1.11-1.37), higher tumor grade (OR 3.58, 95%CI 2.29-5.59), unmarried status (OR 3.5, 95%CI 2.1-5.7), HR-/HER2+ (OR 4.07, 95%CI 3.56-4.67), HR+/HER2+ (OR 2.5, 95%CI 2.24-2.80) and triple-negative subtypes (OR 1.64, 95%CI 1.44-1.86). Poor prognostic factors were the aged (hazard ratio 3.75, 95%CI 3.56-4.67), black race (hazard ratio 1.17, 95%CI 1.03-1.31), triple-negative subtype (hazard ratio 2.23, 95%CI 1.95-2.56) and higher grade (hazard ratio 1.32, 95%CI 1.03-1.68).Conclusion: In conclusion, patients with BCSHM had a poor survival, and only 13.5% of them were alive more than 3 years. Young patients with HER2+ tumors had higher risk for developing BCSHM, but with better prognosis.

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Prognostic Value of Tumor-Infiltrating Lymphocyte Density Assessed Using a Standardized Method Based on Molecular Subtypes and Adjuvant Chemotherapy in Invasive Breast Cancer

Abstract: Measurements of TIL density in routine clinical practice could give useful prognostic information for the triple-negative, HER2-positive, and luminal B (HER2-negative) IBC subtypes, especially for patients administered adjuvant anthracycline.

Cited by 46 publications

References 27 publications

Prevalence of CD8+ cytotoxic lymphocytes in human neoplasms

Prevalence of CD8+ cytotoxic lymphocytes in human neoplasms

Prediction of Response to Neoadjuvant Chemotherapy in Egyptian Patients with Locally Advanced Breast Cancer: The Evolving Role of Tumour Infiltrating Lymphocytes (TILs)

Incidence and Survival Outcomes of Breast Cancer with Synchronous Hepatic Metastases: A Population-Based Study

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