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Effects of tumor-infiltrating lymphocytes on nonresponse rate of neoadjuvant chemotherapy in patients with invasive breast cancer

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Qian, Xiao-Long, Xia, Xiao-Qing, Li, Ya-Qing, Jia, Yu-Mian, Sun, Yuan-Yuan, Song, Yuan-Ming, Xue, Hui-Qin, Hao, Yan-Fei, Wang, Jin, Wang, Xiao-Zi, Liu, Chen-Ying, Zhang, Xin-Min, Zhang, Li-Na, Guo, Xiao-Jing·2023·Scientific Reports
DOI 10.1038/s41598-023-36517-2PMC PMC10247751
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Abstract

High level of tumor-infiltrating lymphocytes (TILs) can predict the rate of total pathological complete remission (tpCR) of breast cancer patients who receive neoadjuvant chemotherapy (NACT). This study focused on evaluating the data of patients whose primary tumor and/or lymph node metastasis show nonresponse (NR) to NACT, trying to provide a basis for the clinical decision which patients will develop NACT resistance. The study included breast cancers from 991 patients who received NACT. ROC curve analysis confirmed that TILs showed significant predictive value for NR of hormone receptor (HR)+HER2− and triple-negative breast cancer (TNBC). Among HR+HER2− breast cancer, TILs ≥ 10% was an independent predictor for low NR rate. Furthermore, positive correlation of TILs with Ki67 index and Miller-Payne grade, and negative correlation with ER and PR H-scores were only identified in this subgroup. In TNBC, TILs ≥ 17.5% was an independent predictor for low NR rate. The predictive value of low TILs on NR may facilitate to screen patients with HR+HER2− or TNBC who may not benefit from NACT. HR+HER2− breast cancer with low levels of TILs should be carefully treated with neoadjuvant chemotherapy, and other alternatives such as neoadjuvant endocrine therapy can be considered.

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Figure 1 TILs of needle biopsy specimens in different molecular subtypes of breast cancer. TILs tumor-infiltrating lymphocytes.
Figure 1 TILs of needle biopsy specimens in different molecular subtypes of breast cancer. TILs tumor-infiltrating lymphocytes.CC BY · PubMed Central
Figure 2 Analysis of factors on tpCR (a) and NR (b) rates in all breast cancer cases after NACT. tpCR total pathological complete remission, NR nonresponse to neoadjuvant chemotherapy, NACT neoadjuvant chemotherapy.
Figure 2 Analysis of factors on tpCR (a) and NR (b) rates in all breast cancer cases after NACT. tpCR total pathological complete remission, NR nonresponse to neoadjuvant chemotherapy, NACT neoadjuvant chemotherapy.CC BY · PubMed Central
Figure 3 Analysis of factors including TILs on tpCR rate, NR rate, and Miller–Payne (MP) grading of HR+HER2− breast cancer cases after NACT. (a) ROC curve analysis of TILs on tpCR rate (AUC = 0.578, SE = 0.104, 95% CI = 0.375–0.782, P = 0.377). (b) ROC curve analysis of TILs on NR rate (AUC = 0.589, SE = 0.038, 95% CI = 0.516–0.663, P = 0.023). (c) Univariate and multivariate analyses of factors on tpCR rate. (d) Univariate and multivariate analyses of factors on NR rate. (e) The difference of MP grade between the high and low TILs groups was analyzed by nonparametric Mann–Whitney U test and P < 0.05 means statistically significant.
Figure 3 Analysis of factors including TILs on tpCR rate, NR rate, and Miller–Payne (MP) grading of HR+HER2− breast cancer cases after NACT. (a) ROC curve analysis of TILs on tpCR rate (AUC = 0.578, SE = 0.104, 95% CI = 0.375–0.782, P = 0.377). (b) ROC curve analysis of TILs on NR rate (AUC = 0.589, SE = 0.038, 95% CI = 0.516–0.663, P = 0.023). (c) Univariate and multivariate analyses of factors on tpCR rate. (d) Univariate and multivariate analyses of factors on NR rate. (e) The difference of MP grade between the high and low TILs groups was analyzed by nonparametric Mann–Whitney U test and P < 0.05 means statistically significant.CC BY · PubMed Central
Figure 4 Analysis of TILs on tpCR rate and NR rate of HER2+ breast cancer after NACT combined with anti HER2 therapy or after NACT alone. (a) ROC curve analysis of TILs on tpCR rate (AUC = 0.592, SE = 0.048, 95% CI = 0.498–0.687, P = 0.053) of cases with anti HER2 therapy. (b) ROC curve analysis of TILs on NR rate (AUC = 0.674, SE = 0.069, 95% CI = 0.540–0.809, P = 0.052) with NACT alone. (c) Univariate and multivariate analyses of TILs on tpCR rate. (d) Univariate and multivariate analyses of TILs on NR rate.
Figure 4 Analysis of TILs on tpCR rate and NR rate of HER2+ breast cancer after NACT combined with anti HER2 therapy or after NACT alone. (a) ROC curve analysis of TILs on tpCR rate (AUC = 0.592, SE = 0.048, 95% CI = 0.498–0.687, P = 0.053) of cases with anti HER2 therapy. (b) ROC curve analysis of TILs on NR rate (AUC = 0.674, SE = 0.069, 95% CI = 0.540–0.809, P = 0.052) with NACT alone. (c) Univariate and multivariate analyses of TILs on tpCR rate. (d) Univariate and multivariate analyses of TILs on NR rate.CC BY · PubMed Central
Figure 5 Analysis of factors including TILs on tpCR rate and NR rate of TNBC cases after NACT. (a) ROC curve analysis of TILs on tpCR rate (AUC = 0.558, SE = 0.065, 95% CI = 0.430–0.686, P = 0.398). (b) ROC curve analysis of TILs on NR rate (AUC = 0.649, SE = 0.063, 95% CI = 0.525–0.773, P = 0.046). (c) Univariate and multivariate analyses of factors on tpCR rate. (d) Univariate and multivariate analyses of factors on NR rate.
Figure 5 Analysis of factors including TILs on tpCR rate and NR rate of TNBC cases after NACT. (a) ROC curve analysis of TILs on tpCR rate (AUC = 0.558, SE = 0.065, 95% CI = 0.430–0.686, P = 0.398). (b) ROC curve analysis of TILs on NR rate (AUC = 0.649, SE = 0.063, 95% CI = 0.525–0.773, P = 0.046). (c) Univariate and multivariate analyses of factors on tpCR rate. (d) Univariate and multivariate analyses of factors on NR rate.CC BY · PubMed Central
Figure 6 Study cohort. Needle biopsy specimens of 991 random cases that received NACT before breast conserving or radical mastectomy were included in this analysis. HR hormone receptor, including estrogen receptor α (ER), and progesterone receptor (PR), TNBC triple-negative breast cancer, NACT neoadjuvant chemotherapy.
Figure 6 Study cohort. Needle biopsy specimens of 991 random cases that received NACT before breast conserving or radical mastectomy were included in this analysis. HR hormone receptor, including estrogen receptor α (ER), and progesterone receptor (PR), TNBC triple-negative breast cancer, NACT neoadjuvant chemotherapy.CC BY · PubMed Central

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Authors
Qian, X.-L., Xia, X.-Q., Li, Y.-Q., Jia, Y.-M., Sun, Y.-Y., Song, Y.-M., Xue, H.-Q., Hao, Y.-F., Wang, J., Wang, X.-Z., Liu, C.-Y., Zhang, X.-M., Zhang, L.-N., & Guo, X.-J.
Affiliations
Tianjin Medical University Cancer Institute and Hospital (CN)
ORCID
Liu, Chen-Ying
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2023-06-07
Volume
13
Issue
1
Pages
9256-9256
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-023-36517-2
PMC
PMC10247751
OpenAlex
W4379767997
Cited by
8
References
0
Citations by year
2026: 1 · 2025: 4 · 2024: 2 · 2023: 1
FWCI
1.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81772840)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › MRI in cancer diagnosis
Keywords
tumor-infiltrating lymphocytes, neoadjuvant chemotherapy, breast cancer, treatment non-response, predictive biomarkers, triple-negative breast cancer, hormone receptor-positive HER2-negative breast cancer, Ki-67, endocrine therapy, lymph node metastasis
MeSH terms
Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Female, Humans, Prognosis, Lymphocytes, Tumor-Infiltrating, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, Neoadjuvant Therapy, Triple Negative Breast Neoplasms

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