CoChat
Sign Up
Cited by 8Breast Cancer Treatment StudiesBreast Lesions and CarcinomasMRI in cancer diagnosis

The DOI matches its Crossref record.

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

Open access
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
Open this paper in CoChat — free accountOpen PDF

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41598-023-36517-2

Cites

Statistics

Figures

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

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

No references could be resolved yet.

Research works printed but not linked: 30

  1. Fisher, E. R., Wang, J., Bryant, J., Fisher, B. & Wolmark, N. Pathobiology of preoperative chemotherapy: Findings from the national surgical adjuvant breast and bowel (NSABP) protocol B-18. Cancer 95, 681–695. https://doi.org/10.1002/cncr.10741 (2002). · DOI
  2. Hortobagyi, G. N. Comprehensive management of locally advanced breast cancer. Cancer 66, 1387. https://doi.org/10.1002/1097-0142(19900915)66:14+3.0.CO;2-I (1990). · DOI
  3. von Minckwitz, G. et al. Trastuzumab emtansine for residual invasive her2-positive breast cancer. New Engl. J. Med. 380, 617–628. https://doi.org/10.1056/NEJMoa1814017 (2018). · DOI
  4. Kuerer, H. M. et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J. Clin. Oncol. 17, 460–469. https://doi.org/10.1200/JCO.1999.17.2.460 (1999). · DOI
  5. Rosenberg, S., Spiess, P. & Lafreniere, R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233, 1318–1321. https://doi.org/10.1126/science.3489291 (1986). · DOI
  6. Tsuta, K. et al. Primary lung adenocarcinoma with massive lymphocyte infiltration. Am. J. Clin. Pathol. 123, 547–552. https://doi.org/10.1309/APKQ-4Q9D-52GN-LR8W (2005). · DOI
  7. Stanton, S. E. & Disis, M. L. Clinical significance of tumor-infiltrating lymphocytes in breast cancer. J. Immunother. Cancer 4, 59. https://doi.org/10.1186/s40425-016-0165-6 (2016). · DOI
  8. Cortazar, P. et al. Pathological complete response and long-term clinical benefit in breast cancer: The CTNeoBC pooled analysis. Lancet 384, 164–172. https://doi.org/10.1016/S0140-6736(13)62422-8 (2014). · DOI
  9. Minckwitz, G. V., Untch, M., Blohmer, J. U., Costa, S. D. & Loibl, S. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J. Clin. Oncol. 30, 1796–1804. https://doi.org/10.1200/JCO.2011.38.8595 (2012). · DOI · Paper page
  10. Ogston, K. N. et al. A new histological grading system to assess response of breast cancers to primary chemotherapy: Prognostic significance and survival. Breast 12, 320–327. https://doi.org/10.1016/S0960-9776(03)00106-1 (2003). · DOI
  11. Sataloff, D. M. et al. Pathologic response to induction chemotherapy in locally advanced carcinoma of the breast: A determinant of outcome. J. Am. Coll. Surg. 180, 297–306 (1995).
  12. Karagiannis, G. S. et al. Neoadjuvant chemotherapy induces breast cancer metastasis through a TMEM-mediated mechanism. Sci. Transl. Med. 9, eaan0026. https://doi.org/10.1126/scitranslmed.aan0026 (2017). · DOI
  13. Keklikoglou, I. et al. Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models. Nat. Cell Biol. 21, 190–202. https://doi.org/10.1038/s41556-018-0256-3 (2019). · DOI
  14. von Minckwitz, G. et al. Response-guided neoadjuvant chemotherapy for breast cancer. J. Clin. Oncol. 31, 3623–3630. https://doi.org/10.1200/JCO.2012.45.0940 (2013). · DOI
  15. Stanton, S. E., Adams, S. & Disis, M. L. Variation in the incidence and magnitude of tumor-infiltrating lymphocytes in breast cancer subtypes: A systematic review. JAMA Oncol. 2, 1354–1360. https://doi.org/10.1001/jamaoncol.2016.1061 (2016). · DOI
  16. Salgado, R. et al. Tumor-infiltrating lymphocytes and associations with pathological complete response and event-free survival in HER2-positive early-stage breast cancer treated with lapatinib and trastuzumab: a secondary analysis of the NeoALTTO trial. JAMA Oncol. 1, 448–454. https://doi.org/10.1001/jamaoncol.2015.0830 (2015). · DOI
  17. Loi, S. et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the finher trial. Eur. Phys. J. D. 41, 485–492. https://doi.org/10.1140/epjd/e2007-00013-1 (2014). · DOI
  18. Luen, S. J. et al. Tumour-infiltrating lymphocytes in advanced HER2-positive breast cancer treated with pertuzumab or placebo in addition to trastuzumab and docetaxel: A retrospective analysis of the cleopatra study. Lancet Oncol. 18, 52–62. https://doi.org/10.1016/S1470-2045(16)30631-3 (2017). · DOI
  19. Hwang, H. W. et al. A nomogram to predict pathologic complete response (pCR) and the value of tumor-infiltrating lymphocytes (TILs) for prediction of response to neoadjuvant chemotherapy (NAC) in breast cancer patients. Breast Cancer Res. Treat. 173, 255–256. https://doi.org/10.1007/s10549-018-4981-x (2019). · DOI
  20. Luen, S. J., Salgado, R., Dieci, M. V., Vingiani, A. & Loi, S. Prognostic implications of residual disease tumor-infiltrating lymphocytes and residual cancer burden in triple-negative breast cancer patients after neoadjuvant chemotherapy. Ann. Oncol. 30, 236–242. https://doi.org/10.1093/annonc/mdy547 (2019). · DOI
  21. Criscitiello, C., Vingiani, A., Maisonneuve, P., Viale, G. & Curigliano, G. Tumor-infiltrating lymphocytes (tils) in ER+/HER2 breast cancer. Breast Cancer Res. Treat. 183, 347–354. https://doi.org/10.1007/s10549-020-05771-7 (2020). · DOI
  22. Denkert, C. et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: A pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 19, 40–50. https://doi.org/10.1016/S1470-2045(17)30904-X (2018). · DOI · Paper page
  23. Rugo, H. et al. Performance of PD-L1 immunohistochemistry assays in unresectable locally advanced or metastatic triple-negative breast cancer: Post hoc analysis of IMpassion130. Ann. Oncol. 30, v858–v859. https://doi.org/10.1093/annonc/mdz394.009 (2019). · DOI · Paper page
  24. Dieci, M. V., Miglietta, F. & Guarneri, V. Immune infiltrates in breast cancer: Recent updates and clinical implications. Cells 10, 223. https://doi.org/10.3390/cells10020223 (2021). · DOI
  25. Prat, A. et al. HER2-enriched subtype and ERBB2 expression in HER2-positive breast cancer treated with dual HER2 blockade. J. Natl. Cancer I(112), 46–54. https://doi.org/10.1093/jnci/djz042 (2020). · DOI
  26. Salgado, R. et al. International TILs Working Group 2014 The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: Recommendations by an International TILs Working Group 2014. Ann. Oncol. 26, 259–271. https://doi.org/10.1093/annonc/mdu450 (2015). · DOI
  27. Qian, X. L. et al. Syndecan binding protein (SDCBP) is over expressed in estrogen recaptor negative breast cancers, and is a potential promoter for tumor proliferation. PLoS ONE 8, e60046. https://doi.org/10.1371/journal.pone.0060046 (2013). · DOI
  28. Hammond, M. E. et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J. Clin. Oncol. 28, 2784–2795. https://doi.org/10.1200/JCO.2009.25.6529 (2010). · DOI
  29. Mccarty, K. S., Szabo, E., Flowers, J. L., Cox, E. B. & Creasman, W. T. Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors. Cancer Res. 46, 4244s–4248s. https://doi.org/10.1016/0304-3835(86)90123-0 (1986). · DOI
  30. Wolff, A. C. et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J. Clin. Oncol. 36, 2105–2122. https://doi.org/10.1200/JCO.2018.77.8738 (2018). · DOI

Cited by

Sorted by citations

See all 8

Metadata

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Effects of tumor-infiltrating lymphocytes on nonresponse rate of neoadjuvant chemotherapy in patients with invasive breast cancer. https://app.cochat.ai/papers/10.1038/s41598-023-36517-2
The paper
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. (2023). Effects of tumor-infiltrating lymphocytes on nonresponse rate of neoadjuvant chemotherapy in patients with invasive breast cancer. Scientific Reports. https://doi.org/10.1038/s41598-023-36517-2