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Research Article
Shinichiro Kashiwagi
Osaka City University Graduate School of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0460-9599
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Purpose: Lymphocytes surrounding the cancer participate in tumor-related immune responses, and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs to index the tumor-microenvironment (TME), and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TILs density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of pre-operative chemotherapy (POC) in BC patients aged less than 45 years and more than 60 years.
Methods: POC was administered to 356 patients. We confirmed and compared TILs density and therapeutic effects in patients aged < 45 years (n=75) and those aged >61 years (n=116). TIL density was evaluated using pre-treatment needle biopsy specimens. Definition and evaluation of TILs was based on the International TILs Working Group 2014.
Results: Based on subtype, younger patients showed significantly higher pathological complete response rates than older patients with hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)+ and HER2-enriched BC. In HR+HER2+BC, the objective response rate was significantly high in younger than in older patients. Further, a significant difference was observed for overall survival between these patients with triple-negative BC.
Conclusions: Our study suggests that younger BC patients possess significantly high TILs density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes.
Keywords
breast cancer, tumor-infiltrating lymphocytes, tumor immune-microenvironment, Age, preoperative chemotherapy
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryFig.S1.tif
Supplementary Fig. S1 Histopathological analysis of TILs density. The TILs density was calculated as average of infiltrating lymphocytes in the tumor stroma from five random fields, and graded as: a) 3 (>50%), b) 2 (10–50%), c) 1 (≤10%), and d) 0 (absent)
- SupplementaryFig.S2.tif
Supplementary Fig. S2 Comparison of disease-free survival (DFS) between high and low TILs density with varied BC subtypes. Kaplan-Meier DFS analysis has been indicated for patients grouped based on their BC subtype as: a) all cases, b) HR+HER2-, c) HR+HER2+, d) HER2-enriched, and e) TNBC. P-values in the figure indicate statistical significance for each comparison obtained using log-rank
- SupplementaryFig.S3.tif
Supplementary Fig. S3 Comparison of overall survival (OS) between high and low TILs density with varied BC subtypes. Kaplan-Meier OS analysis has been indicated for patients grouped based on their BC subtype as: a) all cases, b) HR+HER2-, c) HR+HER2+, d) HER2-enriched, and e) TNBC. P-values in the figure indicate statistical significance for each comparison obtained using log-rank test
- SupplementaryTableS1.docx
- SupplementaryTableS2.docx
- SupplementaryTableS3.docx
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research Article
Shinichiro Kashiwagi
Osaka City University Graduate School of Medicine
Corresponding Author
ORCiD: https://orcid.org/0000-0002-0460-9599
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
The most recent version of this article is available here.
No community comments so far
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Comments: 0
PDF Downloads: ...
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License:
This work is licensed under a CC BY 4.0 License. Read Full License
The most recent version of this article is available here.
Purpose: Lymphocytes surrounding the cancer participate in tumor-related immune responses, and are called tumor-infiltrating lymphocytes (TILs). Several recent reports suggest TILs to index the tumor-microenvironment (TME), and predict the therapeutic effect of chemotherapy. However, only few studies have studied the relationship between age and TILs. Aging reduces host immunity, and we predict that it may also affect TILs. Thus, we hypothesized that older breast cancer (BC) patients may have low TILs density than younger BC patients. Here, we retrospectively analyzed the differences in TILs by age and the therapeutic effects of pre-operative chemotherapy (POC) in BC patients aged less than 45 years and more than 60 years.
Methods: POC was administered to 356 patients. We confirmed and compared TILs density and therapeutic effects in patients aged < 45 years (n=75) and those aged >61 years (n=116). TIL density was evaluated using pre-treatment needle biopsy specimens. Definition and evaluation of TILs was based on the International TILs Working Group 2014.
Results: Based on subtype, younger patients showed significantly higher pathological complete response rates than older patients with hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)+ and HER2-enriched BC. In HR+HER2+BC, the objective response rate was significantly high in younger than in older patients. Further, a significant difference was observed for overall survival between these patients with triple-negative BC.
Conclusions: Our study suggests that younger BC patients possess significantly high TILs density than older patients. These differences may influence the therapeutic efficacy in highly immunogenic subtypes.
Figure 1
Figure 2
Figure 3
This is a list of supplementary files associated with this preprint. Click to download.
- SupplementaryFig.S1.tif
Supplementary Fig. S1 Histopathological analysis of TILs density. The TILs density was calculated as average of infiltrating lymphocytes in the tumor stroma from five random fields, and graded as: a) 3 (>50%), b) 2 (10–50%), c) 1 (≤10%), and d) 0 (absent)
- SupplementaryFig.S2.tif
Supplementary Fig. S2 Comparison of disease-free survival (DFS) between high and low TILs density with varied BC subtypes. Kaplan-Meier DFS analysis has been indicated for patients grouped based on their BC subtype as: a) all cases, b) HR+HER2-, c) HR+HER2+, d) HER2-enriched, and e) TNBC. P-values in the figure indicate statistical significance for each comparison obtained using log-rank
- SupplementaryFig.S3.tif
Supplementary Fig. S3 Comparison of overall survival (OS) between high and low TILs density with varied BC subtypes. Kaplan-Meier OS analysis has been indicated for patients grouped based on their BC subtype as: a) all cases, b) HR+HER2-, c) HR+HER2+, d) HER2-enriched, and e) TNBC. P-values in the figure indicate statistical significance for each comparison obtained using log-rank test
- SupplementaryTableS1.docx
- SupplementaryTableS2.docx
- SupplementaryTableS3.docx
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