Prognostic Role and Clinical Association of Tumor-Infiltrating Lymphocyte, Programmed Death Ligand-1 Expression with Neutrophil- Lymphocyte Ratio in Locally Advanced Triple-Negative Breast Cancer
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Purpose Tumor-infiltrating lymphocyte (TIL), programmed death-ligand 1 (PD-L1) expression and neutrophil- to-lymphocyte ratio (NLR) is associated to immunogenicity and prognosis of breast cancer. We analyzed baseline NLR, changes of NLR, TIL, and PD-L1 during neoadjuvant chemotherapy (NAC) and their clinical implication in triple-negative breast cancer (TNBC). Materials and Methods Between January 2008 to December 2015, 358 TNBC patients were analyzed. Baseline NLR, 50 paired NLR (initial diagnosis, after completion of NAC) and 34 paired tissues (initial diagnosis, surgical specimen after completion of NAC) were collected. Changes of TIL, CD4, CD8, forkhead box P3 (FOXP3), and PD-L1 expression were assessed with immunohistochemical stain. Results Low NLR ( 3.16) was associated to superior survival (overall survival: 41.83 months vs. 36.5 months, p=0.002; disease-free survival [DFS]: 37.85 months vs. 32.14 months, p=0.032). Modest NLR change after NAC (–30% < NLR change < 100%) showed prolonged DFS (38.37 months vs. 22.37 months, p=0.015). During NAC, negative or negative conversion of tumor PD-L1 expression was associated to poor DFS (34.77 months vs. 16.03 months, p=0.037), and same or increased TIL showed trends for superior DFS, but without statistical significance. Positive tumor PD-L1 expression (H-score 5) in baseline or post- NAC tissue was associated to superior DFS (57.6 months vs. 12.5 months, p=0.001 and 53.3 months vs. 18.9 months, p=0.040). Positive stromal PD-L1 expression in baseline was also associated to superior DFS (50.2 months vs. 20.4 months, p=0.002). Conclusion In locally advanced TNBC, baseline NLR, changes of NLR during NAC was associated to survival. Baseline PD-L1 expression and changes of PD-L1 expression in tumor tissue during NAC also showed association to prognosis.
Abstract
Purpose Tumor-infiltrating lymphocyte (TIL), programmed death-ligand 1 (PD-L1) expression and neutrophil- to-lymphocyte ratio (NLR) is associated to immunogenicity and prognosis of breast cancer. We analyzed baseline NLR, changes of NLR, TIL, and PD-L1 during neoadjuvant chemotherapy (NAC) and their clinical implication in triple-negative breast cancer (TNBC). Materials and Methods Between January 2008 to December 2015, 358 TNBC patients were analyzed. Baseline NLR, 50 paired NLR (initial diagnosis, after completion of NAC) and 34 paired tissues (initial diagnosis, surgical specimen after completion of NAC) were collected. Changes of TIL, CD4, CD8, forkhead box P3 (FOXP3), and PD-L1 expression were assessed with immunohistochemical stain. Results Low NLR ( 3.16) was associated to superior survival (overall survival: 41.83 months vs. 36.5 months, p=0.002; disease-free survival [DFS]: 37.85 months vs. 32.14 months, p=0.032). Modest NLR change after NAC (–30% < NLR change < 100%) showed prolonged DFS (38.37 months vs. 22.37 months, p=0.015). During NAC, negative or negative conversion of tumor PD-L1 expression was associated to poor DFS (34.77 months vs. 16.03 months, p=0.037), and same or increased TIL showed trends for superior DFS, but without statistical significance. Positive tumor PD-L1 expression (H-score 5) in baseline or post- NAC tissue was associated to superior DFS (57.6 months vs. 12.5 months, p=0.001 and 53.3 months vs. 18.9 months, p=0.040). Positive stromal PD-L1 expression in baseline was also associated to superior DFS (50.2 months vs. 20.4 months, p=0.002). Conclusion In locally advanced TNBC, baseline NLR, changes of NLR during NAC was associated to survival. Baseline PD-L1 expression and changes of PD-L1 expression in tumor tissue during NAC also showed association to prognosis.
참고문헌 (32)
- Malorni L, "Clinical and biologic features of triple-negative breast cancers in a large cohort of patients with long-term follow-up", Breast Cancer Res Treat, 136, pp.795~804 (2012)
- Lehmann BD, "Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies", J Clin Invest, 121, pp.2750~2767 (2011)
- Pistelli M, "Pre-treatment neutrophil to lymphocyte ratio may be a useful tool in predicting survival in early triple negative breast cancer patients", BMC Cancer, 15, pp.195~ (2015)
- Diakos CI, "Cancer-related inflammation and treatment effectiveness", Lancet Oncol, 15, pp.e493~e450 (2014)
- Orditura M, "Neutrophil to lymphocyte ratio (NLR) for prediction of distant metastasis-free survival (DMFS) in early breast cancer: a propensity score-matched analysis", ESMO Open, 1, pp.e000038~ (2016)
- Azab B, "Usefulness of the neutrophil-to-lymphocyte ratio in predicting short-and long-term mortality in breast cancer patients", Ann Surg Oncol, 19, pp.217~224 (2012)
- Chen Y, "Pretreatment neutrophil-to-lymphocyte ratio is correlated with response to neoadjuvant chemotherapy as an independent prognostic indicator in breast cancer patients : a retrospective study", BMC Cancer, 16, pp.320~ (2016)
- Loi S, "Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy : BIG 02-98", J Clin Oncol, 31, pp.860~867 (2013)
- Zhang L, "Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer", N Engl J Med, 348, pp.203~213 (2003)
- Galon J, "Type, density, and location of immune cells within human colorectal tumors predict clinical outcome", Science, 313, pp.1960~1964 (2006)
- Miyashita M, "Prognostic significance of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in residual tumors and alterations in these parameters after neoadjuvant chemotherapy in triple-negative breast cancer: a retrospective multicenter study", Breast Cancer Res, 17, pp.124~ (2015)
- Chen DS, "Molecular pathways : next-generation immunotherapy : inhibiting programmed death-ligand 1 and programmed death-1", Clin Cancer Res, 18, pp.6580~6587 (2012)
- Patel SP, "PD-L1 expression as a predictive biomarker in cancer immunotherapy", Mol Cancer Ther, 14, pp.847~856 (2015)
- Wimberly H, "PD-L1 expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer", Cancer Immunol Res, 3, pp.326~332 (2015)
- Muenst S, "Expression of programmed death ligand 1(PD-L1)is associated with poor prognosis in human breast cancer", Breast Cancer Res Treat, 146, pp.15~24 (2014)
- Sabatier R, "Prognostic and predictive value of PDL1 expression in breast cancer", Oncotarget, 6, pp.5449~5464 (2015)
- Park IH, "Prognostic implications of tumor-infiltrating lymphocytes in association with programmed death ligand 1 expression in earlystage breast cancer", Clin Breast Cancer, 16, pp.51~58 (2016)
- Pruneri G, "Clinical validity of tumor-infiltrating lymphocytes analysis in patients with triple-negative breast cancer", Ann Oncol, 27, pp.249~256 (2016)
- Pelekanou V, "Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1expression in breast cancer and its clinical significance", Breast Cancer Res, 19, pp.91~ (2017)
- Li X, "Stromal PD-L1 expression is associated with better disease-free survival in triple-negative breast cancer", Am J Clin Pathol, 146, pp.496~502 (2016)
- Muenst S, "The presence of programmed death 1(PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer", Breast Cancer Res Treat, 139, pp.667~676 (2013)
- Hammond ME, "American Society of Clinical Oncology", College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version), 2010, pp.134, e48~e72
- Wolff AC, "Recommendations for human epidermal growth factor receptor 2 testing in breast cancer : American Society of Clinical Oncology", College of American Pathologists clinical practice guideline update, 2014, pp.138, 241~256
- Guthrie GJ, "The systemic inflammation-based neutrophillymphocyte ratio : experience in patients with cancer", Crit Rev Oncol Hematol, 88, pp.218~230 (2013)
- Pelekanou V, "Effects of neoadjuvant chemotherapy(NAC)on tumor infiltrating lymphocytes(TIL)and PD-L1expression in the SWOG S0800 clinical trial", J Clin Oncol, 35(15 Suppl), pp.519~ (2017)[DOI]
- Seo AN, "Tumour-infiltrating CD8+ lymphocytes as an independent predictive factor for pathological complete response to primary systemic therapy in breast cancer", Br J Cancer, 109, pp.2705~2713 (2013)
- Cimino-Mathews A, "PD-L1(B7-H1)expression and the immune tumor microenvironment in primary and metastatic breast carcinomas", Hum Pathol, 47, pp.52~63 (2016)
- Ghebeh H, "FOXP3+ Tregs and B7-H1+", PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy, 2008, pp.8, 57~
- Ohaegbulam KC, "Human cancer immunotherapy with antibodies to the PD-1and PD-L1 pathway", Trends Mol Med, 21, pp.24~33 (2015)
- Hamanishi J, "Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer", Proc Natl Acad Sci U S A, 104, pp.3360~3365 (2007)
- Spranger S, "Up-regulation of PD-L1, IDO, and T(regs)in the melanoma tumor microenvironment is driven by CD8(+)T cells", Sci Transl Med, 5, pp.200~ (2013)[DOI]
- Badoual C, "PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer", Cancer Res, 73, pp.128~138 (2013)