Skip to main content

Advertisement

Log in

Programmed cell death 1 (PD-1) receptor and programmed death ligand 1 (PD-L1) gene expression in primary breast cancer

  • Preclinical study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

The interaction of the programmed cell death 1 (PD-1) receptor on tumor-infiltrating lymphocytes with programmed death ligand 1 (PD-L1) on tumor cells downregulates anti-tumor immunity. This study evaluated associations between PD-1 and PD-L1 expression in primary breast cancer, clinical characteristics, and patient outcomes.

Methods

Microarray data from the Investigation of Serial Studies to predict your therapeutic response with imaging and molecular analysis (I-SPY 1) study (n = 149) was used to evaluate PD-1 and PD-L1 expression. Associations with clinical features and chemotherapy response were determined using Kruskal–Wallis and Wilcoxon rank sum tests, respectively. Recurrence-free survival (RFS) associations were determined with the Cox proportional hazard model. Associations of PD-1 and PD-L1 and selected genes associated with breast cancer, as well as a predictor of olaparib response (PARPi-7), were determined in I-SPY 1 and 2 other datasets: METABRIC (n = 1992) and TCGA (n = 817), using Pearson correlations.

Results

In I-SPY 1, PD-1 expression was higher in triple-negative breast cancer (TNBC) and HER2 + breast cancer (p = 0.003), and grade 2/3 tumors (p = 0.043), and was associated with pathologic complete response (p = 0.006). PD-L1 expression in the lowest quintile was associated with worse RFS, even after subtype adjustment (HR 2.33, p = 0.01). PD-1 and PD-L1 gene expression correlated with the expression of immune-related genes and PARPi-7.

Conclusions

PD-1 expression is higher in breast cancers with aggressive features such as TNBC. Low PD-L1 expression may be an adverse prognostic factor. PD-1 and PD-L1 gene expression correlates with the expression of immune-related and DNA damage repair genes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets used for this study (I-SPY 1, METABRIC, and TCGA) are publically available. I-SPY 1 datasets were accessed in NCBI Gene Expression Omnibus (GEO) (https://identifiers.org/geo:GSE22226), METABRIC data in European Genome-phenome Archive (EGA) (https://identifiers.org/ega.dataset:EGAD00010000210 and https://identifiers.org/ega.dataset:EGAD00010000211), and TCGA data in cBioPortal for CancerGenomics (https://identifiers.org/cbioportal:brca_tcga_pub2015).

Abbreviations

PD-1:

Programmed cell death 1

PD-L1:

Programmed death ligand 1

TNBC:

Triple-negative breast cancer

HR positive disease:

Hormone receptor positive disease

pCR:

Pathologic complete response

RFS:

Recurrence-free survival

References

  1. Keir ME, Butte MJ, Freeman GJ, Sharpe AH (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

    Article  CAS  PubMed  Google Scholar 

  2. McDermott DF, Atkins MB (2013) PD-1 as a potential target in cancer therapy. Cancer Med 2(5):662–673. https://doi.org/10.1002/cam4.106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Thompson RH, Dong H, Lohse CM, Leibovich BC, Blute ML, Cheville JC, Kwon ED (2007) PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res 13(6):1757–1761. https://doi.org/10.1158/1078-0432.ccr-06-2599

    Article  CAS  PubMed  Google Scholar 

  4. Zou W, Chen L (2008) Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 8(6):467–477. https://doi.org/10.1038/nri2326

    Article  CAS  PubMed  Google Scholar 

  5. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366(26):2455–2465. https://doi.org/10.1056/NEJMoa1200694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. U.S. Food and Drug Administration (2020) Keytruda (Pembrolizumab). Available online: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125514s009lbl.pdf. Accessed 5 June 2020

  7. U.S. Food and Drug Administration (2020) Tecentriq (atezolizumab). Available online: http://wwwaccessdata.fda.gov/drugsatfda_docs/label/2016/761041lblpdf Accessed 5 June 2020

  8. 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(22):2108–2121. https://doi.org/10.1056/NEJMoa1809615

    Article  CAS  PubMed  Google Scholar 

  9. Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L (2016) Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol 34(21):2460–2467. https://doi.org/10.1200/jco.2015.64.8931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Emens LA, Braiteh FS, Cassier P, Delord J, Eder JP, Fasso M, Xiao Y, Wang Y, Molinero L, Chen DS, Krop I (2015) Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer (TNBC). Cancer Res 75(15):2859

    Google Scholar 

  11. Rugo HS, Delord JP, Im S, Ott PA, Piha-Paul SA, Bedard PL, Sachdev J, Le Tourneau C, van Brummelen E, Varga A, Saraf S, Pietrangelo D, Karantza V, Tan A (2016) Preliminary efficacy and safety of pembrolizumab (MK-3475) in patients with PD-L1–positive, estrogen receptor-positive (ER+)/HER2-negative advanced breast cancer enrolled in KEYNOTE-028. Cancer Res 76(4):S5-07

    Google Scholar 

  12. Schmid P, Cortes J, Dente R, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Jia L, Karantza V, Zhao J, Aktan G, O’Shaughnessy J (2019) KEYNOTE-522: phase 3 study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo as neoadjuvant treatment, followed by pembro vs pbo as adjuvant treatment for early triple-negative breast cancer (TNBC). Ann Oncol 30(5):v851–v934

    Google Scholar 

  13. Cortes J, Lipatov O, Im S, Goncalves A, Lee KS, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Zambelli S, Harbeck N, Andre F, Dent R, Zhou X, Karantza V, Mejia JA, Winer EP (2019) KEYNOTE-119: phase 3 study of pembrolizumab (pembro) versus single-agent chemotherapy (chemo) for metastatic triple-negative breast cancer (mTNBC). Ann Oncol 30(5):v851–v934

    Google Scholar 

  14. Nanda R, Liu MC, Yau C, Asare S, Hylton N, Van’t Veer L, Perlmutter J, Wallace AM, Chien AJ, Forero-Torres A, Ellis E, Han H, Clark AS, Albain KS, Boughey JC, Elias AD, Berry DA, Yee D, DeMichele A, Esserman L (2017) Pembrolizumab plus standard neoadjuvant therapy for high-risk breast cancer (BC): results from I-SPY 2. J Clin Oncol 35(15):506–506

    Article  Google Scholar 

  15. Gianna L, Huang C, Egle D, Bermejo B, Zamagni C, Thill M, Anton A, Zambelli S, Biachini G, Russo S, Ciruelos E, Greil R, Semiglazov V, Colleoni M, Kelly C, Mariani G, Del Mastro L, Maffeis I, Valagussa P, Viale G (2019) Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple negative, early high-risk and locally advanced breast cancer. NeoTRIPaPDL1 Michelangelo randomized study. San Antonio Breast Cancer Symp. https://doi.org/10.1158/1538-7445.SABCS19-GS3-04

    Article  Google Scholar 

  16. Rugo HS, Loi S, Adams S, Schmid P, Schneeweiss A, Barrios CH, Iwata H, Dieras VC, Winer EP, Kockx M, Peeters D, Chui SY, Lin JC, Duc AN, Viale G, Molinero L, Emens LA (2019) Performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): post-hoc analysis of IMpassion 130. Ann Oncol 30(5):v851–v934

    Google Scholar 

  17. Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Graf S, Ha G, Haffari G, Bashashati A, Russell R, McKinney S, Langerod A, Green A, Provenzano E, Wishart G, Pinder S, Watson P, Markowetz F, Murphy L, Ellis I, Purushotham A, Borresen-Dale AL, Brenton JD, Tavare S, Caldas C, Aparicio S (2012) The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 486(7403):346–352. https://doi.org/10.1038/nature10983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ciriello G, Gatza ML, Beck AH, Wilkerson MD, Rhie SK, Pastore A, Zhang H, McLellan M, Yau C, Kandoth C, Bowlby R, Shen H, Hayat S, Fieldhouse R, Lester SC, Tse GM, Factor RE, Collins LC, Allison KH, Chen YY, Jensen K, Johnson NB, Oesterreich S, Mills GB, Cherniack AD, Robertson G, Benz C, Sander C, Laird PW, Hoadley KA, King TA, Perou CM (2015) Comprehensive molecular portraits of invasive lobular breast cancer. Cell 163(2):506–519. https://doi.org/10.1016/j.cell.2015.09.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Esserman LJ, Berry DA, Cheang MC, Yau C, Perou CM, Carey L, DeMichele A, Gray JW, Conway-Dorsey K, Lenburg ME, Buxton MB, Davis SE, Van’t Veer LJ, Hudis C, Chin K, Wolf D, Krontiras H, Montgomery L, Tripathy D, Lehman C, Liu MC, Olopade OI, Rugo HS, Carpenter JT, Livasy C, Dressler L, Chhieng D, Singh B, Mies C, Rabban J, Chen YY, Giri D, Au A, Hylton N (2012) Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN 6657). Breast Cancer Res Treat 132(3):1049–1062. https://doi.org/10.1007/s10549-011-1895-2

    Article  CAS  PubMed  Google Scholar 

  20. Esserman LJ, Berry DA, DeMichele A, Carey L, Davis SE, Buxton M, Hudis C, Gray JW, Perou C, Yau C, Livasy C, Krontiras H, Montgomery L, Tripathy D, Lehman C, Liu MC, Olopade OI, Rugo HS, Carpenter JT, Dressler L, Chhieng D, Singh B, Mies C, Rabban J, Chen YY, Giri D, Van’t Veer L, Hylton N (2012) Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL–CALGB 150007/150012, ACRIN 6657. J Clin Oncol 30(26):3242–3249. https://doi.org/10.1200/jco.2011.39.2779

    Article  PubMed  PubMed Central  Google Scholar 

  21. Daemen A, Wolf DM, Korkola JE, Griffith OL, Frankum JR, Brough R, Jakkula LR, Wang NJ, Natrajan R, Reis-Filho JS, Lord CJ, Ashworth A, Spellman PT, Gray JW, Van’t Veer LJ (2012) Cross-platform pathway-based analysis identifies markers of response to the PARP inhibitor olaparib. Breast Cancer Res Treat 135(2):505–517. https://doi.org/10.1007/s10549-012-2188-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gatalica Z, Snyder C, Maney T, Ghazalpour A, Holterman DA, Xiao N, Overberg P, Rose I, Basu GD, Vranic S, Lynch HT, Von Hoff DD, Hamid O (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(12):2965–2970. https://doi.org/10.1158/1055-9965.epi-14-0654

    Article  CAS  Google Scholar 

  23. 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(3):334–342. https://doi.org/10.1097/pas.0000000000000780

    Article  PubMed  Google Scholar 

  24. Ghebeh H, Barhoush E, Tulbah A, Elkum N, Al-Tweigeri T, Dermime S (2008) FOXP3+ Tregs and B7–H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: implication for immunotherapy. BMC Cancer 8:57. https://doi.org/10.1186/1471-2407-8-57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O’Shaughnessy J (2020) Pembrolizumab for early triple-negative breast cancer. N Engl J Med 382(9):810–821. https://doi.org/10.1056/NEJMoa1910549

    Article  CAS  PubMed  Google Scholar 

  26. Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L, Rimm DL (2014) In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas. Clin Cancer Res 20(10):2773–2782. https://doi.org/10.1158/1078-0432.ccr-13-2702

    Article  CAS  PubMed  Google Scholar 

  27. Sabatier R, Finetti P, Mamessier E, Adelaide J, Chaffanet M, Ali HR, Viens P, Caldas C, Birnbaum D, Bertucci F (2015) Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget 6(7):5449–5464. https://doi.org/10.18632/oncotarget.3216

    Article  PubMed  Google Scholar 

  28. Baptista MZ, Sarian LO, Derchain SF, Pinto GA, Vassallo J (2016) Prognostic significance of PD-L1 and PD-L2 in breast cancer. Hum Pathol 47(1):78–84. https://doi.org/10.1016/j.humpath.2015.09.006

    Article  CAS  PubMed  Google Scholar 

  29. 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(1):25–34. https://doi.org/10.1111/his.12904

    Article  PubMed  Google Scholar 

  30. 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. https://doi.org/10.1007/s11523-016-0451-8

    Article  PubMed  Google Scholar 

  31. 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(2):459. https://doi.org/10.3390/ijms18020459

    Article  CAS  PubMed Central  Google Scholar 

  32. 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(1):15–24. https://doi.org/10.1007/s10549-014-2988-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Li Z, Dong P, Ren M, Song Y, Qian X, Yang Y, Li S, Zhang X, Liu F (2016) PD-L1 expression is associated with tumor foxp3(+) regulatory t-cell infiltration of breast cancer and poor prognosis of patient. J Cancer 7(7):784–793. https://doi.org/10.7150/jca.14549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. 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(32):33972–33981. https://doi.org/10.18632/oncotarget.5583

    Article  PubMed  PubMed Central  Google Scholar 

  35. Duchnowska R, Peksa R, Radecka B, Mandat T, Trojanowski T, Jarosz B, Czartoryska-Arlukowicz B, Olszewski WP, Och W, Kalinka-Warzocha E, Kozlowski W, Kowalczyk A, Loi S, Biernat W, Jassem J (2016) Immune response in breast cancer brain metastases and their microenvironment: the role of the PD-1/PD-L axis. Breast Cancer Res 18(1):43. https://doi.org/10.1186/s13058-016-0702-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Harter PN, Bernatz S, Scholz A, Zeiner PS, Zinke J, Kiyose M, Blasel S, Beschorner R, Senft C, Bender B, Ronellenfitsch MW, Wikman H, Glatzel M, Meinhardt M, Juratli TA, Steinbach JP, Plate KH, Wischhusen J, Weide B, Mittelbronn M (2015) Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases. Oncotarget 6(38):40836–40849. https://doi.org/10.18632/oncotarget.5696

    Article  PubMed  PubMed Central  Google Scholar 

  37. Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sanchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gomez H, Ryzhov SV, Darcy PK, Arteaga CL, Balko JM (2016) RAS/MAPK activation is associated with reduced tumor-infiltrating lymphocytes in triple-negative breast cancer: therapeutic cooperation between mek and pd-1/pd-l1 immune checkpoint inhibitors. Clin Cancer Res 22(6):1499–1509. https://doi.org/10.1158/1078-0432.ccr-15-1125

    Article  CAS  PubMed  Google Scholar 

  38. Emens LA, Middleton G (2015) The interplay of immunotherapy and chemotherapy: harnessing potential synergies. Cancer Immunol Res 3(5):436–443. https://doi.org/10.1158/2326-6066.cir-15-0064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Chen G, Emens LA (2013) Chemoimmunotherapy: reengineering tumor immunity. Cancer Immunol Immunother 62(2):203–216. https://doi.org/10.1007/s00262-012-1388-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Burstein MD, Tsimelzon A, Poage GM, Covington KR, Contreras A, Fuqua SA, Savage MI, Osborne CK, Hilsenbeck SG, Chang JC, Mills GB, Lau CC, Brown PH (2015) Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res 21(7):1688–1698. https://doi.org/10.1158/1078-0432.ccr-14-0432

    Article  CAS  PubMed  Google Scholar 

  41. Pusztai L, Han H, Yau C, Wolf D, Wallace A, Shatsky R, Helsten T, Boughey J, Haddad T, Stringer-Reasor E, Falkson C, Chien A, Mukhtar R, Elias A, Borges V, Nanda R, Yee D, Kalinsky K, Albain K, Muller A, Kemmer K, Clark A, Issacs C, Thomas A, Hylton N, Symmans W, Perlmutter J, Melisko M, Rugo H, Schwab R, Wilson A, Singhrao R, Asare S, Van’t Veer L, DeMichele A, Sanil A, Berry D, Esserman L (2020) Trial Consortium I-SPY 2 Evaluation of durvalumab in combination with olaparib and paclitaxel in high-risk HER2 negative stage II/III breast cancer: results from the I-SPY 2 trial. AACR Annu Meet. https://doi.org/10.1158/1538-7445.AM2020-CT011

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the I-SPY 1 study participants and staff. The authors would like to acknowledge the Conquer Cancer Foundation of the American Society of Clinical Oncology for providing Dr. Vidula with a Merit Award (2015) for presenting a portion of this work at the 2015 Annual Meeting. They would also like to acknowledge ABC3-Advanced Breast Cancer Third International Consensus Conference for a travel award for Dr. Vidula to present a portion of this work at this conference. While this study was not funded, the I-SPY 1 clinical trial (CALGB 150007/150012; ACRIN 6657) was funded through the Alliance Grant U10CA180821.

Funding

This study was not funded, as it was a retrospective analysis of publically available data.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to study design, data analysis, manuscript preparation, and have read and approved the final manuscript.

Corresponding author

Correspondence to Neelima Vidula.

Ethics declarations

Conflict of interest

The authors do not have any relevant conflicts of interest to disclose.

Ethical approval

This study involved the retrospective review of publically available databases. Therefore, ethics approval and patient consent was not required. However, this study was conducted in accordance with ethical standards of the institution, and standard research ethical practices in the USA.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vidula, N., Yau, C. & Rugo, H.S. Programmed cell death 1 (PD-1) receptor and programmed death ligand 1 (PD-L1) gene expression in primary breast cancer. Breast Cancer Res Treat 187, 387–395 (2021). https://doi.org/10.1007/s10549-021-06234-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-021-06234-3

Keywords

Navigation