- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05250336
Tumor-Infiltrating Lymphocytes and Programmed Cell Death - Ligand 1 in Breast Cancer
Prognostic and Predictive Value of Tumor-Infiltrating Lymphocytes and Programmed Cell Death - Ligand 1 in Breast Cancer
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.
Study Overview
Status
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Vishvak Chanthar
- Phone Number: +91-9840577791
- Email: drvishvak@gmail.com
Study Locations
-
-
Uttar Pradesh
-
Lucknow, Uttar Pradesh, India, 226014
- Recruiting
- Sanjay Gandhi Postgraduate Institute of Medical Sciences
-
Contact:
- Gaurav Agarwal
- Phone Number: +91-522-2494160
- Email: gauravbsi@gmail.com
-
Sub-Investigator:
- Vishvak Chanthar K M M
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
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.
Description
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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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 |
Assessment of Prognostic and Predictive value of Tumor-Infiltrating Lymphocytes and Programmed cell Death - Ligand 1 in Breast cancer
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Correlation of TILs and PDL-1 in various molecular sub-types
Time Frame: Range of 6 months - 6 years follow up
|
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)
Time Frame: a follow up period of 6 months to 6 years
|
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
Time Frame: a follow-up time frame Range from 6 months to 6 years
|
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
Time Frame: Time frame range of 6 months to 6 years follow up
|
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
|
Collaborators and Investigators
Investigators
- Principal Investigator: Gaurav Agarwal, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2018-177-IMP-EXP-4
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Breast Cancer
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); Rutgers Cancer Institute of New JerseyActive, not recruitingStage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedMale Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
Northwestern UniversityEisai Inc.UnknownMale Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative...United States
-
University of WashingtonTerminatedBreast Cancer | Breast Cancer Stage I | Breast Cancer Stage II | Breast Cancer Stage III | Breast Cancer Stage IIB | Breast Cancer Stage IIA | Breast Cancer Stage IIIA | Breast Cancer Stage IIIB | Breast Cancer Stage IIIcUnited States
-
CelgeneCompletedBreast Cancer | Metastatic Breast Cancer | Stage IV Breast Cancer | Triple-negative Breast Cancer | Recurrent Breast Cancer | Breast Tumor | Cancer of the Breast | Triple-negative Metastatic Breast Cancer | Estrogen Receptor- Negative Breast Cancer | HER2- Negative Breast Cancer | Progesterone Receptor- Negative...United States, United Kingdom, Italy, Germany, Spain, Canada, Portugal, Australia, Austria, Greece, Brazil, France
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedHER2-positive Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Estrogen Receptor-negative Breast Cancer | Estrogen Receptor-positive Breast Cancer | Progesterone Receptor-negative Breast Cancer | Progesterone Receptor-positive Breast...United States
-
University of WashingtonNational Cancer Institute (NCI)CompletedHER2-positive Breast Cancer | Male Breast Cancer | Stage IV Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIIC Breast Cancer | Recurrent Breast CancerUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Susan G. Komen Breast Cancer FoundationCompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Triple-negative Breast Cancer | Stage IIIC Breast Cancer | Estrogen Receptor-negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | HER2-negative Breast CancerUnited States
-
Ohio State University Comprehensive Cancer CenterCompletedStage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage IIIC Breast Cancer | Stage III Breast CancerUnited States
Clinical Trials on Observational Study
-
Taysha Gene Therapies, Inc.Withdrawn
-
AstraZenecaRecruitingNon-Small Cell Lung CancerUnited States
-
University of ManitobaCompletedObesity | Pregnancy | Cesarean SectionCanada
-
University of Castilla-La ManchaRecruitingKnee OsteoarthritisSpain
-
AstraZenecaRecruiting
-
Drexel UniversityCompletedOsteoporosisUnited States
-
The Aurum Institute NPCKarolinska Institutet; Ludwig-Maximilians - University of Munich; University... and other collaboratorsUnknownRespiratory Tract Infections | Tuberculosis, PulmonaryMozambique, South Africa, Tanzania, Gambia
-
Oslo University HospitalThe Research Council of NorwayRecruitingMesothelioma | Pseudomyxoma Peritonei | Colorectal Carcinoma | Ovarian CarcinomaNorway
-
Oslo University HospitalThe Research Council of NorwayActive, not recruiting
-
AstraZenecaDaiichi Sankyo, Inc.CompletedBreast CancerUnited States, Germany, Italy, Korea, Republic of, United Kingdom, Portugal, Australia, Japan, Canada, France