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Prediction of lymph node metastasis by tumor-infiltrating lymphocytes in T1 breast cancer
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
View the published version at BMC Cancer.
Background: Lymph node metastasis is more likely in early-stage breast cancer with lower tumor-infiltrating lymphocyte (TIL) density. Therefore, we investigated the correlation between TILs and lymph node metastasis in cT1 breast cancer patients undergoing surgery and the usefulness of TILs in predicting sentinel lymph node metastasis (SLNM) in cT1N0M0 breast cancer.
Methods: We investigated 332 breast cancer patients who underwent surgery as the first-line treatment after preoperative diagnosis of cT1. A positive diagnosis of SLNM as an indication for axillary clearance was defined as macrometastasis in the sentinel lymph node (SLN) (macrometastasis: tumor diameter >2 mm). Semi-quantitative evaluation of lymphocytes infiltrating the peritumoral stroma as TILs in primary tumor biopsy specimens prior to treatment was conducted.
Results: For SLN biopsy (SLNB), a median of 2 (range, 1-8) SLNs were pathologically evaluated. Sixty cases (19.4%) of SLNM (macrometastasis: 46, micrometastasis: 16) were observed. Metastasis was significantly greater in breast cancers with tumor diameter >10 mm than in those with diameter 10 mm (p = 0.016). Metastasis was significantly associated with lymphatic invasion (p <0.001). These two clinicopathological factors correlated with SLNM even in patients diagnosed with cN0 (tumor size; p=0.017, lymphatic invasion; p=0.002). Multivariate analysis for SLNM predictors revealed lymphatic invasion (p=0.008, odds ratio [OR]=2.522) and TILs (p<0.001, OR=0.137) as independent factors.
Conclusions: Our results suggest a correlation between lymph node metastasis and tumor immune-microenvironment in cT1 breast cancer. TIL density may be a predictor of SLNM in breast cancer without lymph node metastasis on preoperative imaging.
Keywords
breast cancer, tumor-infiltrating lymphocytes, tumor immune-microenvironment, lymph node metastasis, sentinel lymph node.
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Reviewer #6 agreed
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This preprint is under consideration at BMC Cancer. A preprint is 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.
Learn more about In Review
Research article
Prediction of lymph node metastasis by tumor-infiltrating lymphocytes in T1 breast cancer
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
Peer Review Timeline
CURRENT STATUS: Published
Version 3
Posted 23 Jun, 2020
No comments provided
Editorial decision: Minor revision
On 18 Jun, 2020
Review #2 received
Received 16 Jun, 2020
Review #1 received
Received 15 Jun, 2020
Review #3 received
Received 28 May, 2020
Reviewer #3 agreed
On 26 May, 2020
Reviewer #4 agreed
On 26 May, 2020
Editor assigned
On 25 May, 2020
Reviewers invited
Invitations sent on 25 May, 2020
Reviewer #1 agreed
On 25 May, 2020
Reviewer #2 agreed
On 25 May, 2020
Submission checks complete
On 24 May, 2020
Editor invited
On 24 May, 2020
No comments provided
Editorial decision: Major revision
On 17 May, 2020
Review #4 received
Received 05 May, 2020
Review #3 received
Received 05 May, 2020
Review #2 received
Received 04 May, 2020
Review #1 received
Received 30 Apr, 2020
Reviewer #7 agreed
On 27 Apr, 2020
Reviewer #6 agreed
On 25 Apr, 2020
Reviewers invited
Invitations sent on 24 Apr, 2020
Reviewer #1 agreed
On 24 Apr, 2020
Reviewer #2 agreed
On 24 Apr, 2020
Reviewer #3 agreed
On 24 Apr, 2020
Reviewer #4 agreed
On 24 Apr, 2020
Reviewer #5 agreed
On 24 Apr, 2020
Editor assigned
On 21 Apr, 2020
First submitted
On 20 Apr, 2020
Submission checks complete
On 20 Apr, 2020
Editor invited
On 20 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at BMC Cancer.
Background: Lymph node metastasis is more likely in early-stage breast cancer with lower tumor-infiltrating lymphocyte (TIL) density. Therefore, we investigated the correlation between TILs and lymph node metastasis in cT1 breast cancer patients undergoing surgery and the usefulness of TILs in predicting sentinel lymph node metastasis (SLNM) in cT1N0M0 breast cancer.
Methods: We investigated 332 breast cancer patients who underwent surgery as the first-line treatment after preoperative diagnosis of cT1. A positive diagnosis of SLNM as an indication for axillary clearance was defined as macrometastasis in the sentinel lymph node (SLN) (macrometastasis: tumor diameter >2 mm). Semi-quantitative evaluation of lymphocytes infiltrating the peritumoral stroma as TILs in primary tumor biopsy specimens prior to treatment was conducted.
Results: For SLN biopsy (SLNB), a median of 2 (range, 1-8) SLNs were pathologically evaluated. Sixty cases (19.4%) of SLNM (macrometastasis: 46, micrometastasis: 16) were observed. Metastasis was significantly greater in breast cancers with tumor diameter >10 mm than in those with diameter 10 mm (p = 0.016). Metastasis was significantly associated with lymphatic invasion (p <0.001). These two clinicopathological factors correlated with SLNM even in patients diagnosed with cN0 (tumor size; p=0.017, lymphatic invasion; p=0.002). Multivariate analysis for SLNM predictors revealed lymphatic invasion (p=0.008, odds ratio [OR]=2.522) and TILs (p<0.001, OR=0.137) as independent factors.
Conclusions: Our results suggest a correlation between lymph node metastasis and tumor immune-microenvironment in cT1 breast cancer. TIL density may be a predictor of SLNM in breast cancer without lymph node metastasis on preoperative imaging.
Figure 1
Figure 2
Figure 3