Expression of Programmed Death Ligand 1 (PD-L1) in Breast Cancer patients in India and its Correlation with Prognostic Parameters Expression of PD-L1 in BC in India

Pallavi Punhanni (1), Charanjeet Ahluwalia (2)
(1) Vardhaman Mahavir Medical College & Safdarjung Hospital, New Delhi, India, India,
(2) Vardhaman Mahavir Medical College & Safdarjung Hospital, New Delhi, India, India

Abstract

Background: The PD-1/PD-L1 pathway represents an adaptive immune resistance mechanism that is exerted by tumor cells. The study was conducted to evaluate the expression of PD-L1 in breast carcinoma in India and to find out its correlation with prognostic parameters. Despite numerous studies, there is a lack of literature for such studies in Indian patients. Moreover, the results obtained from these studies have not been uniform.


Methods: A hospital-based cross-sectional study was conducted on 150 cases of breast carcinoma. The invasive cancer specimens were assessed for routine microscopy and classified into various histopathological subtypes. Bloom Richardson grading was done. Immunohistochemistry for surrogate molecular classification as well as PD-L1 was performed. PD-L1 expression was then compared with several prognostic parameters such as tumor subtype, tumor grade, surrogate molecular classification and pTNM stage. Data analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0. A P value of <0.05 was considered statistically significant.


Results: PD-L1 was positive in 14.67% of patients with score 1 in 6% and score 2 in 8.67% of patients. The PD-L1 expression showed a positive correlation with the tumor of higher grades (grade3). It was significantly higher among IBC with medullary features as compared to IBC-NST, IBC with papillary features and the Lobular type. PD-L1 showed a significant association with surrogate molecular classification as well. Its expression was found to be the highest in Triple negative breast cancer subtype as compared to tumors showing ER/PR positivity (p<0.05). However, there was no significant association between PD-L1 and TNM staging.


Conclusion: This study revealed a significant association between PD-L1 several prognostic factors such as higher tumor grade (grade3), Triple Negative breast cancer, and IBC with the medullary pattern subtype. The association between PD-L1 and such prognostic parameters signifies its role in tumor mechanism and makes it a potential target for immunotherapy especially in Triple Negative breast cancer cases which lack specific targeted therapies. Moreover, paucity of literature on PD-L1 in breast cancer patients in India and the data showing conflicting results make this study valuable. Our study shall be helpful in further adding to the knowledge of PD-L1 expression in breast cancer especially in Indian women.

Full text article

Generated from XML file

References

Breast cancer- WHO. Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer#:~:text=In%202020%2C%20there%20were%202.3,the%20world%27s%20most%20prevalent%20cancer.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225-49.

Najafi S, Sadeghi M, Abasvandi F, Shajari MR, Mohebi K, Ghandchi H. Prognostic factors influencing prognosis in early breast cancer patients. Prz Menopauzalny 2019;18(2):82-8.

Malvia S, Bagadi SA, Dubey US, Saxena S. Epidemiology of breast cancer in Indian women. Asia Pac J Clin Oncol 2017;13:289-95. doi: 10.1111/ajco.12661.

Thakur KK, Bordoloi D, Kunnumakkara AB. Alarming burden of triple-negative breast cancer in India. Clin Breast Cancer 2018;18:393-9. doi: 10.1016/j.clbc.2017.07.013.

Cancer immunotherapy and the PD-1/PD-L1 checkpoint pathway. Available from: https://www.abcam.com/cancer/cancer-immunotherapy-and-the-pd1pdl1-pathway.

Shi Y. Regulatory mechanisms of PD-L1 expression in cancer cells. Cancer Immunol Immunother 2018;262:1-9. doi: 10.1007/s00262-018-2226-9.

Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat. Rev. Cancer. 2016;16:275–287. doi: 10.1038/nrc.2016.36.

Shen X, Zhao B. Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis. BMJ. 2018;362:k3529. doi: 10.1136/bmj.k3529.

Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N. Engl. J. Med. 2018;379:2108–2121. doi: 10.1056/NEJMoa1809615.

Gong J, Chehrazi-Raffle A, Reddi S, Salgia R. Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations. J Immunother Cancer 2018;6(1):8. doi: 10.1186/s40425-018-0316-z.

Planes-Laine G, Rochigneux P, Bertucci F, Chretein AS, Viens P, Sabatier R, et al. PD- 1/PD-L1 Targeting in breast cancer: The first clinical evidences are emerging. A literature review. Cancers (Basel) 2019;11(7):1033. doi: 10.3390/cancers11071033.

Muenst S, Schaerli AR, Gao F, Däster S, Trella E, Droeser RA, et al. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast cancer Res Treat 2014;146:15-24. doi: 10.1007/s10549-014-2988-5.

Botti G, Collina F, Scognamiglio G, Di Bonito M, Liguori G, Cantile M. Programmed death ligand 1 (PDL-1) expression in triple negative breast cancer cells: new proposal for a tumor score definition. Int J Clin Exp Pathol 2016;9:11693-96. Available from:- https://www.scopus.com/record/display.uri?eid=2-s2.0-85006141718&origin=inward&txGid=4b6d22bd14ce62bc9ec5d6fe19f5d192

Layton C, Bancroft JD. The Hematoxylin and Eosin. In: Suvarna SK, Layton C, Bancroft JD (Eds). Theory and Practice of Histological Techniques, 7th edition. Philadelphia: Elsevier; 2013. pp. 179-220.

Collins LC. Breast. Rosai and Ackerman Surgical Pathology, 11th edition. Philadelphia: Elsevier; 2017. pp. 1434-527.

Hortobagyi GN, Connolly JL, D’Orsi CJet al. Breast. In: Amin MB, Edge S, Greene F et al, eds; American Joint Committee on Cancer. AJCC cancer staging manual. 8th ed. New York, NY: Springer, 2017; 589–636.

Uhercik M, Sanders AJ, Owen S, Davies E, Sharma AK, Jiang WJ, et al. Clinical Significance of PD1 and PDL1 in Human Breast Cancer. Anticancer Res 2017;37(8):4249- 54. doi: 10.21873/anticanres.11817

Heimes AS, Schmidt M. Atezolizumab for the treatment of triple-negative breast cancer. Expert Opin Investig Drugs. 2019 Jan;28(1):1-5. doi: 10.1080/13543784.2019.1552255.

Lou J, Zhou Y, Huang J, Qian X. Relationship between PD-L1 expression and clinical characteristics in patients with breast invasive ductal carcinoma. Open Med (Wars) 2017;12:288-92. doi: 10.1515/med-2017-0042.

Doğukan R, Uçak R, Doğukan FM, Tanık C, Çitgez B, Kabukcuoğlu F. Correlation between the expression of pd-l1 and clinicopathological parameters in triple negative breast cancer patients. Eur J Breast Health 2019;15(4):235-41. doi: 10.5152/ejbh.2019.4912.

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

Yuan C, Liu Z, Yu Q, Wang X, Bian M, Yu Z, Yu J. Expression of PD-1/PD-L1 in primary breast tumours and metastatic axillary lymph nodes and its correlation with clinicopathological parameters. Sci Rep. 2019 Oct 7;9(1):14356. doi: 10.1038/s41598-019-50898-3.

Zhou T, Xu D, Tang B, Ren Y, Han Y, Liang G, et al. 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 2018;29(9):904-10. doi: 10.1097/CAD.0000000000000683.

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

Gatalica Z, Snyder C, Maney T, Ghazalpour A, Holterman DA, Xiao, et al. Programmed cell death 1 (PD-1) and its ligand (PD-L1) in common cancers and their correlation with molecular cancer type. Cancer Epidemiol Biomarkers Prevention 2014;23:2965-70. doi: 10.1158/1055-9965.EPI-14-0654.

Lotfinejad P, Asghari Jafarabadi M, Abdoli Shadbad M, Kazemi T, Pashazadeh F, Sandoghchian Shotorbani S, et al. Prognostic Role and Clinical Significance of Tumor-Infiltrating Lymphocyte (TIL) and Programmed Death Ligand 1 (PD-L1) Expression in Triple-Negative Breast Cancer (TNBC): A Systematic Review and Meta-Analysis Study. Diagnostics (Basel). 2020 Sep 17;10(9):704. doi: 10.3390/diagnostics10090704.

Constantinou C, Papadopoulos S, Karyda E, Alexopoulos A, Agnanti N, Batistatou A et al.Expression and clinical significance of Claudin-7, PDL-1, PTEN, c-Kit, c-Met,c-Myc, ALK, CK5/6, CK17, p53, EGFR, Ki67, p63 in triple-negative breast cancer–a single centre prospective observational study. In Vivo 2018;32:303-11. doi: 10.21873/invivo.11238.

Authors

Pallavi Punhanni
pallavi.punhani@gmail.com (Primary Contact)
Charanjeet Ahluwalia
Author Biographies

Pallavi Punhanni, Vardhaman Mahavir Medical College & Safdarjung Hospital, New Delhi, India

MD PATHOLOGY

SENIOR RESIDENT

VMMC AND SAFDARJUNG HOSPITAL, NEW DELHI, INDIA

Charanjeet Ahluwalia, Vardhaman Mahavir Medical College & Safdarjung Hospital, New Delhi, India

DNB PATHOLOGY

SENIOR SPECIALIST

Department of Pathology, VMMC and Safdarjung Hospital , New Delhi, India

1.
Punhanni P, Ahluwalia C. Expression of Programmed Death Ligand 1 (PD-L1) in Breast Cancer patients in India and its Correlation with Prognostic Parameters: Expression of PD-L1 in BC in India. Arch Breast Cancer [Internet]. 2023 May 14 [cited 2024 Dec. 10];10(3):280-9. Available from: https://www.archbreastcancer.com/index.php/abc/article/view/700

Article Details

Similar Articles

You may also start an advanced similarity search for this article.