Tumor-Infiltrating Lymphocytes and Programmed Cell Death - Ligand 1 in Breast Cancer

NCT05250336 | Unknown

• 1 other identifier: 2018-177-IMP-EXP-4
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 1

Brief Summary

The morphological evaluation of Tumor-infiltrating Lymphocytes (TILs) in breast cancer is gaining momentum as evidence strengthens for the clinical relevance of this immunological biomarker. In breast cancer (BC) lesions, TILs are seen in intratumoral and stromal areas. TILs are predictive of response to treatment and this association appears to be strongest in Triple-negative (TNBC) and Her 2 (Human epidermal growth factor receptor) positive breast cancer subtypes. Contrastingly, the association in Estrogen Receptor (ER) positive, HER 2 negative tumors have not been established. Programmed cell death 1 (PD-1), are receptors expressed on the surface of T, B, and Natural killer cells and in some tumor cells. These attenuate the cellular immune response by inducing T-cell apoptosis. Programmed Cell Death Ligand 1 (PD-L1) overexpression is reported to be associated with large tumor size, lymph node metastasis, and ER-negativity. Importantly, PD-L1 is expressed more frequently in TNBC patients. High PD-L1 expression may be a prognostic indicator for reduced overall survival6. This information may be helpful to screen candidates for anti-PD-1/PD-L1 therapy, especially patients with TNBC The aim of this study is to characterize the cohort of patients with breast cancer based on a semiquantitative assessment of TILs and to correlate the concentration of TILs and PD-L1 in various intrinsic subtypes (based on Immunohistochemistry) with the overall outcome. Also to correlate the TILs and PD-L1 expression with tumor response to Neoadjuvant Chemotherapy (NACT) and to stratify the predictive value of this biomarker in TNBC.

Conditions

Breast Cancer; Tumor Infiltrating Lymphocytes; Programmed Cell Death Ligand 1

Outcome Measures

Primary Outcomes (4)

• Correlation of TILs and PDL-1 in various molecular sub-types

  To Correlate the concentration of TILs and PD-L1 in various intrinsic subtypes (based on Immunohistochemistry) with the overall outcome

  Range of 6 months - 6 years follow up

• PDL-1 expression in patients with Triple Negative Breast Cancer (TNBC)

  To Correlate PDL-1 expression with outcomes in patients with TNBC

  a follow up period of 6 months to 6 years

• TILs and Tumor response to treatment

  To Correlate the TILs with tumor response to Neoadjuvant Chemotherapy and to stratify the predictive value of this biomarker

  a follow-up time frame Range from 6 months to 6 years

• PD-L1 expression and Tumor response to treatment

  To Correlate PD-L1 expression with response to Neoadjuvant Chemotherapy in patients with TNBC

  Time frame range of 6 months to 6 years follow up

Study Arms (1)

Patients with Primary Breast Cancer

The pretherapeutic cores or specimen from patients who meet the following criteria were subjected for analysis INCLUSION CRITERIA Primary Breast cancer Completed scheduled treatment at SGPGI Adequate quality histopathology material available in Department of Pathology archives With minimum 6 months follow up EXCLUSION CRITERIA Insufficient data Incomplete treatment Insufficient follow up information Insufficient histological material for review

Other: Observational Study

Interventions

Observational Study OTHER

Assessment of Prognostic and Predictive value of Tumor-Infiltrating Lymphocytes and Programmed cell Death - Ligand 1 in Breast cancer

Patients with Primary Breast Cancer

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This is a time-bound study, where we include all patients treated between January 2016 and December 2021 who meet the inclusion criteria. We had screened out approximately 2000 patients treated over this period, of which about 1000 have met the inclusion criteria.

You may qualify if:

• Primary Breast cancer
• Completed scheduled treatment at SGPGI
• Adequate quality histopathology material available in Department of Pathology archives
• With minimum 6 months follow up

You may not qualify if:

• Insufficient data
• Incomplete treatment
• Insufficient follow up information
• Insufficient histological material for review

Sponsors & Collaborators

• Sanjay Gandhi Postgraduate Institute of Medical Sciences: lead

Study Sites (1)

Sanjay Gandhi Postgraduate Institute of Medical Sciences

Lucknow, Uttar Pradesh, 226014, India

RECRUITING

Related Publications (5)

• Wein L, Savas P, Luen SJ, Virassamy B, Salgado R, Loi S. Clinical Validity and Utility of Tumor-Infiltrating Lymphocytes in Routine Clinical Practice for Breast Cancer Patients: Current and Future Directions. Front Oncol. 2017 Aug 3;7:156. doi: 10.3389/fonc.2017.00156. eCollection 2017.

  PMID: 28824872 BACKGROUND

• Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D, Kellokumpu-Lehtinen PL, Bono P, Kataja V, Desmedt C, Piccart MJ, Loibl S, Denkert C, Smyth MJ, Joensuu H, Sotiriou C. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann Oncol. 2014 Aug;25(8):1544-50. doi: 10.1093/annonc/mdu112. Epub 2014 Mar 7.

  PMID: 24608200 BACKGROUND

• Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, Wienert S, Van den Eynden G, Baehner FL, Penault-Llorca F, Perez EA, Thompson EA, Symmans WF, Richardson AL, Brock J, Criscitiello C, Bailey H, Ignatiadis M, Floris G, Sparano J, Kos Z, Nielsen T, Rimm DL, Allison KH, Reis-Filho JS, Loibl S, Sotiriou C, Viale G, Badve S, Adams S, Willard-Gallo K, Loi S; International TILs Working Group 2014. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015 Feb;26(2):259-71. doi: 10.1093/annonc/mdu450. Epub 2014 Sep 11.

  PMID: 25214542 BACKGROUND

• Denkert C, von Minckwitz G, Brase JC, Sinn BV, Gade S, Kronenwett R, Pfitzner BM, Salat C, Loi S, Schmitt WD, Schem C, Fisch K, Darb-Esfahani S, Mehta K, Sotiriou C, Wienert S, Klare P, Andre F, Klauschen F, Blohmer JU, Krappmann K, Schmidt M, Tesch H, Kummel S, Sinn P, Jackisch C, Dietel M, Reimer T, Untch M, Loibl S. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol. 2015 Mar 20;33(9):983-91. doi: 10.1200/JCO.2014.58.1967. Epub 2014 Dec 22.

  PMID: 25534375 BACKGROUND

• Agarwal G, Vishvak Chanthar KMM, Katiyar S, Kumari N, Krishnani N, Sabaretnam M, Chand G, Mishra A, Lal P. Predictive and Prognostic Role of Tumor-Infiltrating Lymphocytes in Patients with Advanced Breast Cancer Treated with Primary Systemic Therapy. World J Surg. 2023 May;47(5):1238-1246. doi: 10.1007/s00268-023-06912-x. Epub 2023 Feb 3.

  PMID: 36735048 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Observation

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Gaurav Agarwal

  Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vishvak Chanthar

CONTACT

+91-9840577791; drvishvak@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Endocrine and Breast Surgery

Study Record Dates

• First Submitted: February 11, 2022
• First Posted: February 22, 2022
• Study Start: January 19, 2019
• Primary Completion: June 30, 2022
• Study Completion: September 30, 2022
• Last Updated: February 22, 2022

Record last verified: 2022-02

Locations

IN (1)