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Prognostic and clinicopathological value of PD-L1 expression in primary breast cancer: a meta-analysis

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Abstract

Purpose

To evaluate the association between PD-L1 expression (PD-L1+) and clinicopathological characteristics and effect on prognosis in primary breast cancer (PBC).

Methods

A systematic search of the PubMed, Web of Science, and Embase databases was conducted in November 2018. Studies detecting PD-L1 using immunohistochemistry, and concerning its prognostic or clinicopathological significance in PBC were included. The HR with 95% CI for survival, and the events for clinicopathological features were pooled.

Results

Forty-seven studies were included, with a total of 14,367 PBC patients. PD-L1+ tumor cells (TCs) were associated with ductal carcinomas, large tumor size, histological Grade 3 tumors, high Ki-67, ER and PR negative, and triple-negative breast cancer; and also, related to high tumor-infiltrating lymphocytes (TILs) and PD-1 expression. PD-L1+ TCs were significantly associated with shorter disease-free survival (DFS, HR = 1.43, 95% CI 1.21–1.70, P < 0.0001) and overall survival (OS, HR = 1.58, 95% CI 1.14–2.20, P = 0.006). And the HRs of PD-L1+ TCs on DFS and OS were higher (1.48 and 1.70, respectively) and homogeneous when using whole tissue section, compared with tumor microarrays. However, PD-L1+ TILs related to better DFS (HR = 0.45, 95% CI 0.28–0.73, P = 0.001) and OS (HR = 0.41, 95% CI 0.27–0.63, P < 0.0001).

Conclusion

PD-L1 expression on TCs associates with high-risk clinicopathological parameters and poor prognosis in PBC patients, while PD-L1+ TILs may relate to a better survival. Comprehensive assessment of TCs and TILs is required when evaluating the clinical relevance of PD-L1 expression in future studies.

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References

  1. Gibney GT, Weiner LM, Atkins MB (2016) Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol 17:e542–e551. https://doi.org/10.1016/s1470-2045(16)30406-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hansen JD, Du Pasquier L, Lefranc MP, Lopez V, Benmansour A, Boudinot P (2009) The B7 family of immunoregulatory receptors: a comparative and evolutionary perspective. Mol Immunol 46:457–472. https://doi.org/10.1016/j.molimm.2008.10.007

    Article  CAS  PubMed  Google Scholar 

  3. Okazaki T, Honjo T (2007) PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol 19:813–824. https://doi.org/10.1093/intimm/dxm057

    Article  CAS  PubMed  Google Scholar 

  4. Ma G, Deng Y, Jiang H, Li W, Wu Q, Zhou Q (2018) The prognostic role of programmed cell death-ligand 1 expression in non-small cell lung cancer patients: an updated meta-analysis. Clin Chim Acta 482:101–107. https://doi.org/10.1016/j.cca.2018.03.038

    Article  CAS  PubMed  Google Scholar 

  5. Gandini S, Massi D, Mandala M (2016) PD-L1 expression in cancer patients receiving anti PD-1/PD-L1 antibodies: a systematic review and meta-analysis. Crit Rev Oncol Hematol 100:88–98. https://doi.org/10.1016/j.critrevonc.2016.02.001

    Article  PubMed  Google Scholar 

  6. Wang Q, Liu F, Liu L (2017) Prognostic significance of PD-L1 in solid tumor: an updated meta-analysis. Medicine (Baltimore) 96:e6369. https://doi.org/10.1097/md.0000000000006369

    Article  CAS  Google Scholar 

  7. Buzdar AU, Blumenschein GR, Smith TL, Powell KC, Hortobagyi GN, Yap HY, Schell FC, Barnes BC, Ames FC, Martin RG et al (1984) Adjuvant chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide, with or without Bacillus Calmette-Guerin and with or without irradiation in operable breast cancer. A prospective randomized trial. Cancer 53:384–389

    Article  CAS  Google Scholar 

  8. Stovgaard ES, Dyhl-Polk A, Roslind A, Balslev E, Nielsen D (2019) PD-L1 expression in breast cancer: expression in subtypes and prognostic significance: a systematic review. Breast Cancer Res Treat 174:571–584. https://doi.org/10.1007/s10549-019-05130-1

    Article  CAS  PubMed  Google Scholar 

  9. Stovgaard ES, Nielsen D, Hogdall E, Balslev E (2018) Triple negative breast cancer—prognostic role of immune-related factors: a systematic review. Acta Oncol 57:74–82. https://doi.org/10.1080/0284186x.2017.1400180

    Article  CAS  PubMed  Google Scholar 

  10. Esteva FJ, Hubbard-Lucey VM, Tang J, Pusztai L (2019) Immunotherapy and targeted therapy combinations in metastatic breast cancer. Lancet Oncol 20:e175–e186. https://doi.org/10.1016/s1470-2045(19)30026-9

    Article  CAS  PubMed  Google Scholar 

  11. Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, Dieras V, Hegg R, Im SA, Shaw Wright G, Henschel V, Molinero L, Chui SY, Funke R, Husain A, Winer EP, Loi S, Emens LA (2018) Atezolizumab and Nab-Paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379:2108–2121. https://doi.org/10.1056/NEJMoa1809615

    Article  CAS  PubMed  Google Scholar 

  12. Adams S, Loi S, Toppmeyer D, Cescon DW, De Laurentiis M, Nanda R, Winer EP, Mukai H, Tamura K, Armstrong A, Liu MC, Iwata H, Ryvo L, Wimberger P, Rugo HS, Tan AR, Jia L, Ding Y, Karantza V, Schmid P (2019) Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study. Ann Oncol 30:405–411. https://doi.org/10.1093/annonc/mdy518

    Article  CAS  PubMed  Google Scholar 

  13. Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, Awada A, Cescon DW, Iwata H, Campone M, Nanda R, Hui R, Curigliano G, Toppmeyer D, O’Shaughnessy J, Loi S, Paluch-Shimon S, Tan AR, Card D, Zhao J, Karantza V, Cortes J (2018) Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase 2 KEYNOTE-086 study. Ann Oncol 30:397–404. https://doi.org/10.1093/annonc/mdy517

    Article  Google Scholar 

  14. Ghebeh H, Mohammed S, Al-Omair A, Qattan A, Lehe C, Al-Qudaihi G, Elkum N, Alshabanah M, Amer SB, Tulbah A, Ajarim D, Al-Tweigeri T, Dermime SD (2006) The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors. Neoplasia 8:190–198. https://doi.org/10.1593/neo.05733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Muenst S, Schaerli AR, Gao F, Daster S, Trella E, Droeser RA, Muraro MG, Zajac P, Zanetti R, Gillanders WE, Weber WP, Soysal SD (2014) Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat 146:15–24. https://doi.org/10.1007/s10549-014-2988-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Li X, Li M, Lian Z, Zhu H, Kong L, Wang P, Yu J (2016) Prognostic role of programmed death ligand-1 expression in breast cancer: a systematic review and meta-analysis. Target Oncol 11:753–761. https://doi.org/10.1007/s11523-016-0451-8

    Article  PubMed  Google Scholar 

  17. Zhang M, Sun H, Zhao S, Wang Y, Pu H, Wang Y, Zhang Q (2017) Expression of PD-L1 and prognosis in breast cancer: a meta-analysis. Oncotarget 8:31347–31354. https://doi.org/10.18632/oncotarget.15532

    Article  PubMed  PubMed Central  Google Scholar 

  18. Guo Y, Yu P, Liu Z, Maimaiti Y, Wang S, Yin X, Liu C, Huang T (2016) Prognostic and clinicopathological value of programmed death ligand-1 in breast cancer: a meta-analysis. PLoS ONE 11:e0156323. https://doi.org/10.1371/journal.pone.0156323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bae SB, Cho HD, Oh MH, Lee JH, Jang SH, Hong SA, Cho J, Kim SY, Han SW, Lee JE, Kim HJ, Lee HJ (2016) Expression of programmed death receptor ligand 1 with high tumor infiltrating lymphocytes is associated with better prognosis in breast cancer. J. Breast Cancer 19:242–251. https://doi.org/10.4048/jbc.2016.19.3.242

    Article  PubMed  PubMed Central  Google Scholar 

  20. Beckers RK, Selinger CI, Vilain R, Madore J, Wilmott JS, Harvey K, Holliday A, Cooper CL, Robbins E, Gillett D, Kennedy CW, Gluch L, Carmalt H, Mak C, Warrier S, Gee HE, Chan C, McLean A, Walker E, McNeil CM, Beith JM, Swarbrick A, Scolyer RA, O’Toole SA (2016) Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome. Histopathology 69:25–34. https://doi.org/10.1111/his.12904

    Article  PubMed  Google Scholar 

  21. Botti G, Collina F, Scognamiglio G, Rao F, Peluso V, De Cecio R, Piezzo M, Landi G, De Laurentiis M, Cantile M, Di Bonito M (2017) Programmed death ligand 1 (PD-L1) tumor expression is associated with a better prognosis and diabetic disease in triple negative breast cancer patients. Int J Mol Sci 18:459. https://doi.org/10.3390/ijms18020459

    Article  CAS  PubMed Central  Google Scholar 

  22. Zhao T, Li C, Wu Y, Li B, Zhang B (2017) Prognostic value of PD-L1 expression in tumor infiltrating immune cells in cancers: a meta-analysis. PLoS ONE 12:e.0176822. https://doi.org/10.1371/journal.pone.0176822

    Article  CAS  Google Scholar 

  23. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(264–269):w264

    Article  Google Scholar 

  24. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605. https://doi.org/10.1007/s10654-010-9491-z

    Article  PubMed  Google Scholar 

  25. Ali HR, Glont SE, Blows FM, Provenzano E, Dawson SJ, Liu B, Hiller L, Dunn J, Poole CJ, Bowden S, Earl HM, Pharoah PDP, Caldas C (2015) PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes. Ann Oncol 26:1488–1493. https://doi.org/10.1093/annonc/mdv192

    Article  CAS  PubMed  Google Scholar 

  26. Lee J, Kim DM, Lee A (2018) 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. Cancer Res Treat 51:649–663. https://doi.org/10.4143/crt.2018.270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Thompson ED, Taube JM, Asch-Kendrick RJ, Ogurtsova A, Xu HY, Sharma R, Meeker A, Argani P, Emens LA, Cimino-Mathews A (2017) PD-L1 expression and the immune microenvironment in primary invasive lobular carcinomas of the breast. Mod Pathol 30:1551–1560. https://doi.org/10.1038/modpathol.2017.79

    Article  CAS  PubMed  Google Scholar 

  28. Tomioka N, Azuma M, Ikarashi M, Yamamoto M, Sato M, Watanabe KI, Yamashiro K, Takahashi M (2018) The therapeutic candidate for immune checkpoint inhibitors elucidated by the status of tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression in triple negative breast cancer (TNBC). Breast Cancer 25:34–42. https://doi.org/10.1007/s12282-017-0781-0

    Article  PubMed  Google Scholar 

  29. Joneja U, Vranic S, Swensen J, Feldman R, Chen W, Kimbrough J, Xiao N, Reddy S, Palazzo J, Gatalica Z (2017) Comprehensive profiling of metaplastic breast carcinomas reveals frequent overexpression of programmed death-ligand 1. J Clin Pathol 70:255–259. https://doi.org/10.1136/jclinpath-2016-203874

    Article  CAS  PubMed  Google Scholar 

  30. Barrett MT, Lenkiewicz E, Malasi S, Basu A, Yearley JH, Annamalai L, McCullough AE, Kosiorek HE, Narang P, Wilson Sayres MA, Chen M, Anderson KS, Pockaj BA (2018) The association of genomic lesions and PD-1/PD-L1 expression in resected triple-negative breast cancers. Breast Cancer Res 20:71. https://doi.org/10.1186/s13058-018-1004-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Buisseret L, Garaud S, de Wind A, Van den Eynden G, Boisson A, Solinas C, Gu-Trantien C, Naveaux C, Lodewyckx JN, Duvillier H, Craciun L, Veys I, Larsimont D, Piccart-Gebhart M, Stagg J, Sotiriou C, Willard-Gallo K (2017) Tumor-infiltrating lymphocyte composition, organization and PD-1/PD-L1 expression are linked in breast cancer. Oncoimmunology 6:e1257452. https://doi.org/10.1080/2162402x.2016.1257452

    Article  PubMed  Google Scholar 

  32. Dill EA, Gru AA, Atkins KA, Friedman LA, Moore ME, Bullock TN, Cross JV, Dillon PM, Mills AM (2017) PD-L1 expression and intratumoral heterogeneity across breast cancer subtypes and stages an assessment of 245 primary and 40 metastatic tumors. Am J Surg Pathol 41:334–342. https://doi.org/10.1097/pas.0000000000000780

    Article  PubMed  Google Scholar 

  33. Guo L, Li WB, Zhu XX, Ling Y, Qiu T, Dong L, Fang Y, Yang HY, Ying JM (2016) PD-L1 expression and CD274 gene alteration in triple-negative breast cancer: implication for prognostic biomarker. Springerplus 5:805. https://doi.org/10.1186/s40064-016-2513-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Sun WY, Lee YK, Koo JS (2016) Expression of PD-L1 in triple-negative breast cancer based on different immunohistochemical antibodies. J Transl Med 14:173. https://doi.org/10.1186/s12967-016-0925-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Cerbelli B, Pernazza A, Botticelli A, Fortunato L, Monti M, Sciattella P, Campagna D, Mazzuca F, Mauri M, Naso G, Marchetti P, d’Amati G, Costarelli L (2017) PD-L1 expression in TNBC: a predictive biomarker of response to neoadjuvant chemotherapy? Biomed Res Int. https://doi.org/10.1155/2017/1750925

    Article  PubMed  PubMed Central  Google Scholar 

  36. Choi SH, Chang JS, Koo JS, Park JW, Sohn JH, Keum KC, Suh CO, Kim YB (2018) Differential prognostic impact of strong PD-L1 expression and 18F-FDG uptake in triple-negative breast cancer. Am J Clin Oncol 2:2. https://doi.org/10.1097/coc.0000000000000426

    Article  Google Scholar 

  37. Adams TA, Vail PJ, Ruiz A, Mollaee M, McCue PA, Knudsen ES, Witkiewicz AK (2018) Composite analysis of immunological and metabolic markers defines novel subtypes of triple negative breast cancer. Mod Pathol 31:288–298. https://doi.org/10.1038/modpathol.2017.126

    Article  CAS  PubMed  Google Scholar 

  38. Li XX, Wetherilt CS, Krishnamurti U, Yang J, Ma YM, Styblo TM, Meisel JL, Peng LM, Siddiqui MT, Cohen C, Aneja R (2016) Stromal PD-L1 expression is associated with better disease-free survival in triple-negative breast cancer. Am J Clin Pathol 146:496–502. https://doi.org/10.1093/ajcp/aqw134

    Article  CAS  PubMed  Google Scholar 

  39. Mori H, Kubo M, Yamaguchi R, Nishimura R, Osako T, Arima N, Okumura Y, Okido M, Yamada M, Kai M, Kishimoto J, Oda Y, Nakamura M (2017) The combination of PD-L1 expression and decreased tumorinfiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer. Oncotarget 8:15584–15592. https://doi.org/10.18632/oncotarget.14698

    Article  PubMed  PubMed Central  Google Scholar 

  40. Ren XY, Wu HW, Lu JL, Zhang YH, Luo YF, Xu QQ, Shen SJ, Liang ZY (2018) PD1 protein expression in tumor infiltrated lymphocytes rather than PDL1 in tumor cells predicts survival in triple-negative breast cancer. Cancer Biol Ther 19:373–380. https://doi.org/10.1080/15384047.2018.1423919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Wang YX, Dong TY, Xuan QJ, Zhao H, Qin L, Zhang QY (2018) Lymphocyte-activation gene-3 expression and prognostic value in neoadjuvant-treated triple-negative breast cancer. J Breast Cancer 21:124–133. https://doi.org/10.4048/jbc.2018.21.2.124

    Article  PubMed  PubMed Central  Google Scholar 

  42. Kim A, Lee SJ, Kim YK, Park WY, Park DY, Kim JY, Lee CH, Gong G, Huh GY, Choi KU (2017) Programmed death-ligand 1 (PD-L1) expression in tumour cell and tumour infiltrating lymphocytes of HER2-positive breast cancer and its prognostic value. Sci Rep 7:11671. https://doi.org/10.1038/s41598-017-11905-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Li M, Li AQ, Zhou SL, Xu Y, Xiao YX, Bi R, Yang WT (2018) Heterogeneity of PD-L1 expression in primary tumors and paired lymph node metastases of triple negative breast cancer. BMC Cancer 18:4. https://doi.org/10.1186/s12885-017-3916-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Li YC, Opyrchal M, Yao S, Peng X, Yan L, Jabbour H, Khoury T (2018) The role of programmed death ligand-1 and tumor-infiltrating lymphocytes in breast cancer overexpressing HER2 gene. Breast Cancer Res Treat 170:293–302. https://doi.org/10.1007/s10549-018-4745-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hou Y, Nitta H, Wei L, Banks PM, Lustberg M, Wesolowski R, Ramaswamy B, Parwani AV, Li Z (2018) PD-L1 expression and CD8-positive T cells are associated with favorable survival in HER2-positive invasive breast cancer. Cancer Sci 24:911–919. https://doi.org/10.1111/tbj.13112

    Article  CAS  Google Scholar 

  46. Hou Y, Nitta H, Parwani A, Li Z (2018) Evaluating the expression of mismatch repair proteins and checkpoint immune markers and their association in triple-negative and HER2-positive breast cancers. Lab Invest 98:72. https://doi.org/10.1038/labinvest.2018.3

    Article  Google Scholar 

  47. Arias-Pulido H, Cimino-Mathews A, Chaher N, Qualls C, Joste N, Colpaert C, Marotti JD, Foisey M, Prossnitz ER, Emens LA, Fiering S (2018) The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome. Breast Cancer Res Treat 171:273–282. https://doi.org/10.1007/s10549-018-4834-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Cimino-Mathews A, Thompson E, Taube JM, Ye XB, Lu Y, Meeker A, Xu HY, Sharma R, Lecksell K, Cornish TC, Cuka N, Argani P, Emens LA (2016) PD-L1 (B7-H1) expression and the immune tumor microenvironment in primary and metastatic breast carcinomas. Hum Pathol 47:52–63. https://doi.org/10.1016/j.humpath.2015.09.003

    Article  CAS  PubMed  Google Scholar 

  49. He J, Huo L, Ma JS, Zhao J, Bassett RL, Sun XP, Ueno NT, Lim B, Gong Y (2018) Expression of programmed death ligand 1 (PD-L1) in posttreatment primary inflammatory breast cancers and clinical implications. Am J Clin Pathol 149:253–261. https://doi.org/10.1093/ajcp/aqx162

    Article  PubMed  PubMed Central  Google Scholar 

  50. Wang ZQ, Milne K, Derocher H, Webb JR, Nelson BH, Watson PH (2017) PD-L1 and intratumoral immune response in breast cancer. Oncotarget 8:51641–51651. https://doi.org/10.18632/oncotarget.18305

    Article  PubMed  PubMed Central  Google Scholar 

  51. Baptista MZ, Sarian LO, Derchain SFM, Pinto GA, Vassallo J (2016) Prognostic significance of PD-L1 and PD-L2 in breast cancer. Hum Pathol 47:78–84. https://doi.org/10.1016/j.humpath.2015.09.006

    Article  CAS  PubMed  Google Scholar 

  52. Tsang JYS, Au WL, Lo KY, Ni YB, Hlaing T, Hu JT, Chan SK, Chan KF, Cheung SY, Tse GM (2017) PD-L1 expression and tumor infiltrating PD-1 + lymphocytes associated with outcome in HER2 + breast cancer patients. Breast Cancer Res Treat 162:19–30. https://doi.org/10.1007/s10549-016-4095-2

    Article  CAS  PubMed  Google Scholar 

  53. Qin T, Zeng YD, Qin G, Xu F, Lu JB, Fang WF, Xue C, Zhan JH, Zhang XK, Zheng QF, Peng RJ, Yuan ZY, Zhang L, Wang SS (2015) High PD-L1 expression was associated with poor prognosis in 870 Chinese patients with breast cancer. Oncotarget 6:33972–33981. https://doi.org/10.18632/oncotarget.5583

    Article  PubMed  PubMed Central  Google Scholar 

  54. Polonia A, Pinto R, Cameselle-Teijeiro JF, Schmitt FC, Paredes J (2017) Prognostic value of stromal tumour infiltrating lymphocytes and programmed cell death-ligand 1 expression in breast cancer. J Clin Pathol 70:860–867. https://doi.org/10.1136/jclinpath-2016-203990

    Article  CAS  PubMed  Google Scholar 

  55. Li ZH, Dong PZ, Ren MJ, Song YW, Qian XL, Yang YL, Li S, Zhang XM, Liu FF (2016) PD-L1 expression is associated with tumor FOXP3(+) regulatory T-cell infiltration of breast cancer and poor prognosis of patient. J. Cancer 7:784–793. https://doi.org/10.7150/jca.14549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Park IH, Kong SY, Ro JY, Kwon Y, Kang JH, Mo HJ, Jung SY, Lee S, Lee KS, Kang HS, Lee E, Joo J, Ro J (2016) Prognostic implications of tumor-infiltrating lymphocytes in association with programmed death ligand 1 expression in early-stage breast cancer. Clin Breast Cancer 16:51–58. https://doi.org/10.1016/j.clbc.2015.07.006

    Article  CAS  PubMed  Google Scholar 

  57. Okabe M, Toh U, Iwakuma N, Saku S, Akashi M, Kimitsuki Y, Seki N, Kawahara A, Ogo E, Itoh K, Akagi Y (2017) Predictive factors of the tumor immunological microenvironment for long-term follow-up in early stage breast cancer. Cancer Sci 108:81–90. https://doi.org/10.1111/cas.13114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sobral-Leite M, Van de Vijver K, Michaut M, van der Linden R, Hooijer GKJ, Horlings HM, Severson TM, Mulligan AM, Weerasooriya N, Sanders J, Glas AM, Wehkamp D, Mittempergher L, Kersten K, Cimino-Mathews A, Peters D, Hooijberg E, Broeks A, van de Vijver MJ, Bernards R, Andrulis IL, Kok M, de Visser KE, Schmidt MK (2018) Assessment of PD-L1 expression across breast cancer molecular subtypes, in relation to mutation rate, BRCA1-like status, tumor-infiltrating immune cells and survival. OncoImmunology 7:e1509820. https://doi.org/10.1080/2162402X.2018.1509820

    Article  PubMed  PubMed Central  Google Scholar 

  59. Chen S, Wang RX, Liu Y, Yang WT, Shao ZM (2017) PD-L1 expression of the residual tumor serves as a prognostic marker in local advanced breast cancer after neoadjuvant chemotherapy. Int J Cancer 140:1384–1395. https://doi.org/10.1002/ijc.30552

    Article  CAS  PubMed  Google Scholar 

  60. Zhou TT, Xu D, Tang BF, Ren YL, Han YR, Liang GG, Wang J, Wang L (2018) Expression of programmed death ligand-1 and programmed death-1 in samples of invasive ductal carcinoma of the breast and its correlation with prognosis. Anticancer Drugs 29:904–910. https://doi.org/10.1097/cad.0000000000000683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lou J, Zhou YF, Huang JH, Qian XJ (2017) Relationship between PD-L1 expression and clinical characteristics in patients with breast invasive ductal carcinoma. Open Med 12:288–292. https://doi.org/10.1515/med-2017-0042

    Article  CAS  Google Scholar 

  62. Li F, Ren Y, Wang ZD (2018) Programmed death 1 ligand 1 expression in breast cancer and its association with patients’ clinical parameters. J Cancer Res Ther 14:150–154. https://doi.org/10.4103/jcrt.JCRT_602_17

    Article  PubMed  Google Scholar 

  63. Asano Y, Kashiwagi S, Goto W, Takada K, Takahashi K, Morisaki T, Fujita H, Takashima T, Tomita S, Ohsawa M, Hirakawa K, Ohira M (2018) Prediction of treatment responses to neoadjuvant chemotherapy in triple-negative breast cancer by analysis of immune checkpoint protein expression. J Transl Med 16:87. https://doi.org/10.1186/s12967-018-1458-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. McLemore LE, Janakiram M, Albanese J, Shapiro N, Lo YT, Zang XX, Fineberg S (2018) An immunoscore using PD-L1, CD68, and tumor-infiltrating lymphocytes (TILs) to predict response to neoadjuvant chemotherapy in invasive breast cancer. Appl Immunohistochem Mol Morphol 26:611–619. https://doi.org/10.1097/pai.0000000000000485

    Article  CAS  PubMed  Google Scholar 

  65. Kitano A, Ono M, Yoshida M, Noguchi E, Shimomura A, Shimoi T, Kodaira M, Yunokawa M, Yonemori K, Shimizu C, Kinoshita T, Fujiwara Y, Tsuda H, Tamura K (2017) Tumour-infiltrating lymphocytes are correlated with higher expression levels of PD-1 and PD-L1 in early breast cancer. ESMO Open 2:e000150. https://doi.org/10.1136/esmoopen-2016-000150

    Article  PubMed  PubMed Central  Google Scholar 

  66. Pelekanou V, Barlow WE, Nahleh ZA, Wasserman B, Lo YC, von Wahlde MK, Hayes D, Hortobagyi GN, Gralow J, Tripathy D, Porter P, Szekely B, Hatzis C, Rimm DL, Pusztai L (2018) Tumor-infiltrating lymphocytes and pd-l1 expression in pre- and posttreatment breast cancers in the SWOG S0800 phase II neoadjuvant chemotherapy trial. Mol Cancer Ther 17:1324–1331. https://doi.org/10.1158/1535-7163.MCT-17-1005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Wang C, Zhu H, Zhou Y, Mao F, Lin Y, Pan B, Zhang X, Xu Q, Huang X, Sun Q (2017) Prognostic value of PD-L1 in breast cancer: a meta-analysis. Breast J 23:436–443. https://doi.org/10.1111/tbj.12753

    Article  CAS  PubMed  Google Scholar 

  68. Kim HM, Lee J, Koo JS (2017) Clinicopathological and prognostic significance of programmed death ligand-1 expression in breast cancer: a meta-analysis. BMC Cancer 17:690. https://doi.org/10.1186/s12885-017-3670-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Mittendorf EA, Philips AV, Meric-Bernstam F, Qiao N, Wu Y, Harrington S, Su X, Wang Y, Gonzalez-Angulo AM, Akcakanat A, Chawla A, Curran M, Hwu P, Sharma P, Litton JK, Molldrem JJ, Alatrash G (2014) PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res 2:361–370. https://doi.org/10.1158/2326-6066.cir-13-0127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Rehman JA, Han G, Carvajal-Hausdorf DE, Wasserman BE, Pelekanou V, Mani NL, McLaughlin J, Schalper KA, Rimm DL (2017) Quantitative and pathologist-read comparison of the heterogeneity of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer. Mod Pathol 30:340–349. https://doi.org/10.1038/modpathol.2016.186

    Article  CAS  PubMed  Google Scholar 

  71. Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, Bossuyt V, Pusztai L, Lannin DR, Rimm DL (2015) PD-L1 expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer. Cancer Immunol Res 3:326–332. https://doi.org/10.1158/2326-6066.cir-14-0133

    Article  CAS  PubMed  Google Scholar 

  72. Kim HR, Ha SJ, Hong MH, Heo SJ, Koh YW, Choi EC, Kim EK, Pyo KH, Jung I, Seo D, Choi J, Cho BC, Yoon SO (2016) PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients. Sci Rep 6:36956. https://doi.org/10.1038/srep36956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Parsa AT, Waldron JS, Panner A, Crane CA, Parney IF, Barry JJ, Cachola KE, Murray JC, Tihan T, Jensen MC, Mischel PS, Stokoe D, Pieper RO (2007) Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med 13:84–88. https://doi.org/10.1038/nm1517

    Article  CAS  PubMed  Google Scholar 

  74. Atefi M, Avramis E, Lassen A, Wong DJ, Robert L, Foulad D, Cerniglia M, Titz B, Chodon T, Graeber TG, Comin-Anduix B, Ribas A (2014) Effects of MAPK and PI3 K pathways on PD-L1 expression in melanoma. Clin Cancer Res 20:3446–3457. https://doi.org/10.1158/1078-0432.ccr-13-2797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Noman MZ, Desantis G, Janji B, Hasmim M, Karray S, Dessen P, Bronte V, Chouaib S (2014) PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med 211:781–790. https://doi.org/10.1084/jem.20131916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors are pleased to acknowledge the suggestions from Professor Xu Liang and Xiaoran Liu, which are crucial for manuscript revision.

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  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, No. 52, Fucheng Road, Haidian District, Beijing, 100142, China

    Wenfa Huang, Ran Ran, Bin Shao & Huiping Li

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  1. Wenfa Huang
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Huang, W., Ran, R., Shao, B. et al. Prognostic and clinicopathological value of PD-L1 expression in primary breast cancer: a meta-analysis. Breast Cancer Res Treat 178, 17–33 (2019). https://doi.org/10.1007/s10549-019-05371-0

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