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Breast Cancer Research and Treatment

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10.01.2019 | Review

PD-L1 expression in breast cancer: expression in subtypes and prognostic significance: a systematic review

verfasst von: Elisabeth Specht Stovgaard, Anne Dyhl-Polk, Anne Roslind, Eva Balslev, Dorte Nielsen

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 3/2019

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Abstract

Purpose

To systematically review the literature on the expression of PD-L1 in primary BC, variation of expression between subtypes and effect on overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS). Additionally, for studies in the neoadjuvant setting, we have reviewed the ability of PD-L1 to predict pathological complete response (pCR).

Methods

Articles included in this review were retrieved by searching PubMed (1966–2018) and EMBASE (1980–2018). The following search terms were used: “PD-L1 expression” and “breast cancer” (PubMed234; EMBASE 161).

Results

Thirty-seven articles were found relevant to this study. We summarize important findings from these works, and show that the observed PD-L1 expression in the studies varies greatly, with expression rates ranging from 0 to 83% across subtypes. PD-L1 expression in relation to prognosis both in the adjuvant and neoadjuvant chemotherapy setting remains controversial, with studies finding better, worse, or no effect on prognosis. We also show that a wide variety of strategies are used when evaluating PD-L1 immunohistochemically, e.g., different cut-off points, different cell types evaluated, and different perceptions of when a cell is positive for PD-L1 (cytoplasmic vs membrane staining).

Conclusion

Further investigation of PD-L1 expression in breast cancer and its effect on prognosis is required. There is little consensus on the methods used to evaluate PD-L1 expression immunohistochemically, and this may contribute to the diverging results found in this study.

Barnet MB, Cooper WA, Boyer MJ et al (2018) Immunotherapy in non-small cell lung cancer: shifting prognostic paradigms. J Clin Med. https://doi.org/10.3390/jcm7060151 CrossRefPubMedPubMedCentral

Marconcini R, Spagnolo F, Stucci LS et al (2018) Current status and perspectives in immunotherapy for metastatic melanoma. Oncotarget 9(15):12452–12470. https://doi.org/10.18632/oncotarget.23746 CrossRefPubMedPubMedCentral

Polk A, Svane I-M, Andersson M et al (2018) Checkpoint inhibitors in breast cancer—current status. Cancer Treat Rev 63:122–134. https://doi.org/10.1016/j.ctrv.2017.12.008 CrossRefPubMed

Tolba MF, Omar HA (2018) Immunotherapy, an evolving approach for the management of triple negative breast cancer: converting non-responders to responders. Crit Rev Oncol Hematol 122:202–207. https://doi.org/10.1016/j.critrevonc.2018.01.005 CrossRefPubMed

Rugo HS, Delord J-P, Im S-A et al (2018) Safety and antitumor activity of pembrolizumab in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. Clin Cancer Res 24:2804–2811. https://doi.org/10.1158/1078-0432.CCR-17-3452 CrossRefPubMed

Perou CM, Sørlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406:747–752. https://doi.org/10.1038/35021093 CrossRefPubMed

Ali HR, Glont S-EE, Blows FM et al (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 CrossRefPubMed

Tsang JYS, Au W-L, Lo K-Y et al (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 CrossRefPubMed

Botti G, Collina F, Scognamiglio G et al (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. https://doi.org/10.3390/ijms18020459 CrossRefPubMedPubMedCentral

10.

Ghebeh H, Tulbah A, Mohammed S et al (2007) Expression of B7-H1 in breast cancer patients is strongly associated with high proliferative Ki-67-expressing tumor cells. Int J Cancer 121:751–758. https://doi.org/10.1002/ijc.22703 CrossRefPubMed

11.

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

12.

Prat A, Pineda E, Adamo B et al (2015) Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast 24:S26–S35. https://doi.org/10.1016/j.breast.2015.07.008 CrossRefPubMed

13.

Cheang MCU, Martin M, Nielsen TO et al (2015) Defining breast cancer intrinsic subtypes by quantitative receptor expression. Oncologist 20:474–482. https://doi.org/10.1634/theoncologist.2014-0372 CrossRefPubMedPubMedCentral

14.

Nielsen TO, Hsu FD, Jensen K et al (2004) Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res 10(16):5367–5374. https://doi.org/10.1158/1078-0432.CCR-04-0220 CrossRefPubMed

15.

Keir ME, Butte MJ, Freeman GJ et al (2008) PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26:677–704. https://doi.org/10.1146/annurev.immunol.26.021607.090331 CrossRefPubMed

16.

Cimino-Mathews A, Thompson E, Taube JM et al (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 CrossRefPubMed

17.

Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12:252–264. https://doi.org/10.1038/nrc3239 CrossRefPubMedPubMedCentral

18.

Ribas A, Hu-Lieskovan S (2016) What does PD-L1 positive or negative mean? J Exp Med 213:2835–2840. https://doi.org/10.1084/jem.20161462 CrossRefPubMedPubMedCentral

19.

Taube JM, Anders RA, Young GD et al (2012) Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 4:127ra37. https://doi.org/10.1126/scitranslmed.3003689 CrossRefPubMedPubMedCentral

20.

Bedognetti D, Hendrickx W, Marincola FM et al (2015) Prognostic and predictive immune gene signatures in breast cancer. Curr Opin Oncol 27:433–444. https://doi.org/10.1097/CCO.0000000000000234 CrossRefPubMed

21.

Buisseret L, Garaud S, de Wind A et al (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 CrossRefPubMed

22.

Schalper KA (2014) PD-L1 expression and tumor-infiltrating lymphocytes. Oncoimmunology 3:e29288. https://doi.org/10.4161//onci.29288 CrossRefPubMedPubMedCentral

23.

Wimberly H, Brown JR, Schalper K et al (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 CrossRefPubMed

24.

Ghebeh H, Mohammed S, Al-Omair A et al (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 CrossRefPubMedPubMedCentral

25.

Schalper KA, Velcheti V, Carvajal D et al (2014) In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas. Clin Cancer Res 20:2773–2782. https://doi.org/10.1158/1078-0432.CCR-13-2702 CrossRefPubMed

26.

Bae SB, Cho HD, Oh M-H et al (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 CrossRefPubMedPubMedCentral

27.

Baptista MZ, Sarian LO, Derchain SFM et al (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 CrossRefPubMed

28.

Beckers RK, Selinger CI, Vilain R et al (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 CrossRefPubMed

29.

Sabatier R, Finetti P, Mamessier E et al (2015) Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget 6:5449–5464. https://doi.org/10.18632/oncotarget.3216 CrossRefPubMed

30.

Qin T, Zeng Y, Qin G et al (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 CrossRefPubMedPubMedCentral

31.

Mori H, Kubo M, Yamaguchi R et al (2017) The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer. Oncotarget 8:15584–15592. https://doi.org/10.18632/oncotarget.14698 CrossRefPubMedPubMedCentral

32.

Gandini S, Massi D, Mandalà 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 CrossRefPubMed

33.

Aguiar PN, De Mello RA, Hall P et al (2017) PD-L1 expression as a predictive biomarker in advanced non-small-cell lung cancer: updated survival data. Immunotherapy 9:499–506. https://doi.org/10.2217/imt-2016-0150 CrossRefPubMed

34.

Zou W, Wolchok JD, Chen L (2016) PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers, and combinations. Sci Transl Med 8:328rv4. https://doi.org/10.1126/scitranslmed.aad7118 CrossRefPubMedPubMedCentral

35.

Karnik T, Kimler BF, Fan F et al (2018) PD-L1 in breast cancer: comparative analysis of 3 different antibodies. Hum Pathol 72:28–34. https://doi.org/10.1016/j.humpath.2017.08.010 CrossRefPubMed

36.

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 CrossRefPubMedPubMedCentral

37.

Udall M, Rizzo M, Kenny J et al (2018) PD-L1 diagnostic tests: a systematic literature review of scoring algorithms and test-validation metrics. Diagn Pathol 13:12. https://doi.org/10.1186/s13000-018-0689-9 CrossRefPubMedPubMedCentral

38.

Sakane T, Murase T, Okuda K et al (2018) A comparative study of PD-L1 immunohistochemical assays with four reliable antibodies in thymic carcinoma. Oncotarget 9:6993–7009. https://doi.org/10.18632/oncotarget.24075 CrossRefPubMedPubMedCentral

39.

Roche Ventana. http://www.ventana.com/ventana-pd-l1-sp263-assay-2/. Accessed 13 June 2018

40.

Muenst S, Schaerli AR, Gao F et al (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 CrossRefPubMedPubMedCentral

41.

Gatalica Z, Snyder C, Maney T et al (2014) Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type. Cancer Epidemiol Biomark Prev 23:2965–2970. https://doi.org/10.1158/1055-9965.EPI-14-0654 CrossRef

42.

Park IH, Kong S-Y, Ro JY et al (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 CrossRefPubMed

43.

Li Z, Dong P, Ren M et al (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 CrossRefPubMedPubMedCentral

44.

Okabe M, Toh U, Iwakuma N et al (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 CrossRefPubMedPubMedCentral

45.

Joneja U, Vranic S, Swensen J et al (2017) Comprehensive profiling of metaplastic breast carcinomas reveals frequent overexpression of programmed death-ligand 1 (2017). J Clin Pathol 70:255–259. https://doi.org/10.1136/jclinpath-2016-203874 CrossRefPubMed

46.

Wang Z-Q, Milne K, Derocher H et al (2017) PD-L1 and intratumoral immune response in breast cancer. Oncotarget 8(31):51641–51651. https://doi.org/10.18632/oncotarget.18305 CrossRefPubMedPubMedCentral

47.

Polónia A, Pinto R, Cameselle-Teijeiro JF et al (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 CrossRefPubMed

48.

Kim A, Lee SJ, Kim YK et al (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 CrossRefPubMedPubMedCentral

49.

Tung N, Garber JE, Hacker MR et al (2016) Prevalence and predictors of androgen receptor and programmed death-ligand 1 in BRCA1-associated and sporadic triple-negative breast cancer. NPJ breast cancer 2:16002. https://doi.org/10.1038/npjbcancer.2016.2 CrossRefPubMedPubMedCentral

50.

Guo L, Li W, Zhu X et al (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 CrossRefPubMedPubMedCentral

51.

Nanda R, Chow LQM, Dees EC et al (2016) Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol 34:2460–2467. https://doi.org/10.1200/JCO.2015.64.8931 CrossRefPubMedPubMedCentral

52.

Adams TA, Vail PJ, Ruiz A et al (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 CrossRefPubMed

53.

Choi SH, Chang JS, Koo JS et al (2018) Differential prognostic impact of strong PD-L1 expression and 18F-FDG uptake in triple-negative breast cancer. Am J Clin Oncol. https://doi.org/10.1097/COC.0000000000000426 CrossRefPubMedPubMedCentral

54.

Mittendorf EA, Philips AV, Meric-Bernstam F et al (2017) PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res 2:361–370. https://doi.org/10.1158/2326-6066.CIR-13-0127 CrossRef

55.

AiErken N, Shi H-J, Zhou Y et al (2017) High PD-L1 expression is closely associated with tumor-infiltrating lymphocytes and leads to good clinical outcomes in chinese triple negative breast cancer patients. Int J Biol Sci 13:1172–1179. https://doi.org/10.7150/ijbs.20868 CrossRefPubMedPubMedCentral

56.

Lou J, Zhou Y, Huang J et al (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 CrossRef

57.

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

58.

Dill EA, Gru AA, Atkins KA et al (2017) PD-L1 expression and intratumoral heterogeneity across breast cancer subtypes and stages. Am J Surg Pathol 41:334–342. https://doi.org/10.1097/PAS.0000000000000780 CrossRefPubMed

59.

McLemore LE, Janakiram M, Albanese J et al (2017) 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(9):611–619. https://doi.org/10.1097/PAI.0000000000000485 CrossRef

60.

Kitano A, Ono M, Yoshida M et al (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 CrossRefPubMedPubMedCentral

61.

Pelekanou V, Barlow WE, Nahleh ZA et al (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 CrossRefPubMedPubMedCentral

62.

Cerbelli B, Pernazza A, Botticelli A et al (2017) PD-L1 Expression in TNBC: a predictive biomarker of response to neoadjuvant chemotherapy? Biomed Res Int 2017:1750925. https://doi.org/10.1155/2017/1750925 CrossRefPubMedPubMedCentral

63.

Wang Y, Dong T, Xuan Q et al (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 CrossRefPubMedPubMedCentral

64.

Hou Y, Nitta H, Wei L et al (2018) Evaluation of immune reaction and PD-L1 expression using multiplex immunohistochemistry in HER2-positive breast cancer: the association with response to anti-HER2 neoadjuvant therapy. Clin Breast Cancer 18:e237–e244. https://doi.org/10.1016/j.clbc.2017.11.001 CrossRefPubMed

65.

Büttner R, Gosney JR, Skov BG et al (2017) Programmed death-ligand 1 immunohistochemistry testing: a review of analytical assays and clinical implementation in non-small-cell lung cancer. J Clin Oncol 35:3867–3876. https://doi.org/10.1200/JCO.2017.74.7642 CrossRefPubMed

66.

Gniadek TJ, Li QK, Tully E et al (2017) Heterogeneous expression of PD-L1 in pulmonary squamous cell carcinoma and adenocarcinoma: implications for assessment by small biopsy. Mod Pathol 30:530–538. https://doi.org/10.1038/modpathol.2016.213 CrossRefPubMed

67.

Li M, Li A, Zhou S et al (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 CrossRefPubMedPubMedCentral

68.

Ogiya R, Niikura N, Kumaki N et al (2016) Comparison of tumor-infiltrating lymphocytes between primary and metastatic tumors in breast cancer patients. Cancer Sci 107:1730–1735. https://doi.org/10.1111/cas.13101 CrossRefPubMedPubMedCentral

69.

Zins K, Heller G, Mayerhofer M et al (2018) Differential prognostic impact of interleukin-34 mRNA expression and infiltrating immune cell composition in intrinsic breast cancer subtypes. Oncotarget 9:23126–23148. https://doi.org/10.18632/oncotarget.25226 CrossRefPubMedPubMedCentral

70.

Salgado R, Denkert C, Campbell C et al (2015) 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 CrossRefPubMedPubMedCentral

71.

Schmid P, Adams S, Rugo HS et al (2018) Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med 379(22):2108–2121. https://doi.org/10.1056/NEJMoa1809615 CrossRefPubMed

Titel: PD-L1 expression in breast cancer: expression in subtypes and prognostic significance: a systematic review
verfasst von: Elisabeth Specht Stovgaard
Anne Dyhl-Polk
Anne Roslind
Eva Balslev
Dorte Nielsen
Publikationsdatum: 10.01.2019
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 3/2019
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05130-1

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Springer Medizin

PD-L1 expression in breast cancer: expression in subtypes and prognostic significance: a systematic review

Abstract

Purpose

Methods

Results

Conclusion

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Abstract

Purpose

Methods

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Conclusion

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