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

NCT ID: NCT05250336

Last Updated: 2022-02-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

1000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-01-19

Study Completion Date

2022-09-30

Brief Summary

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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.

Detailed Description

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This is a retrospective and prospective study in patients with Primary Breast cancer at Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGI). This is a time-bound study, where we include all patients treated between January 2016 and December 2021 who meet the inclusion criteria. We screened out approximately 2000 patients treated over this period, of which about 1000 had met inclusion criteria.

The electronic and physical records of all breast cancer patients maintained in Hospital Information System and Department of Breast and Endocrine Surgery at SGPGI have been screened to identify all appropriate cases and their clinical data were reviewed.

The cohort of patients who met the inclusion criteria was identified from the screened data.

The paraffin blocks of pre-therapeutic core biopsies/ surgical specimens of the study subjects were retrieved and the same from prospective study subjects were included.

Existing data on Immunohistochemistry (IHC) for ER (Estrogen Receptor), PR (Progesterone Receptor), Her 2 neu (Human epidermal growth factor receptor) was tabulated to identify TNBC cohort.

Hematoxylin \& Eosin stained histological slides were reviewed by one set of pathologists for semi quantification of TILs.

TILs have been analyzed both as continuous parameters and in three predefined groups of Low: 0-10%; Intermediate:11 - 59 % and high: ≥ 60 % stromal TILs. In patients with TNBC, the paraffin blocks were retrieved and PD-L1 expression was assessed by IHC.

At this point in time, the recruitment of subjects and semi-quantification of TILs and PDL-1 were over and the analysis/correlation part is yet to be done.

In all study subjects, the concentration of TILs will be correlated with the clinicopathological outcome (treatment response, overall survival, disease-free survival ) and this association will be compared between intrinsic subtypes based on IHC.

In patients treated with Neoadjuvant Chemotherapy (NACT), correlation of TILs with response to NACT (pathologic complete response, partial/static/progression) will be done.

Correlation of PDL-1 expression with outcomes (overall survival, disease-free survival) and with response to Neoadjuvant Chemotherapy (pathologic complete response, partial/static/progression) in patients with Triple Negative Breast Cancer will be done.

The study information obtained will be statistically analyzed to identify the significance of the aforementioned correlations.

Conditions

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Breast Cancer Tumor Infiltrating Lymphocytes Programmed Cell Death Ligand 1

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

OTHER

Study Groups

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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

Observational Study

Intervention Type OTHER

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

Interventions

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Observational Study

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

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sanjay Gandhi Postgraduate Institute of Medical Sciences

OTHER_GOV

Sponsor Role lead

Responsible Party

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Gaurav Agarwal

Professor of Endocrine and Breast Surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Gaurav Agarwal

Role: PRINCIPAL_INVESTIGATOR

Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

Locations

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Sanjay Gandhi Postgraduate Institute of Medical Sciences

Lucknow, Uttar Pradesh, India

Site Status RECRUITING

Countries

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India

Central Contacts

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Vishvak Chanthar

Role: CONTACT

+91-9840577791

Facility Contacts

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Gaurav Agarwal

Role: primary

+91-522-2494160

References

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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.

Reference Type BACKGROUND
PMID: 28824872 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24608200 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25214542 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25534375 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36735048 (View on PubMed)

Other Identifiers

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2018-177-IMP-EXP-4

Identifier Type: -

Identifier Source: org_study_id

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