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

Breast Cancer Clinical Trial

Official title:

Prognostic and Predictive Value of Tumor-Infiltrating Lymphocytes and Programmed Cell Death - Ligand 1 in Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05250336
• Other study ID #: 2018-177-IMP-EXP-4
• Status: Recruiting
• Start date: January 19, 2019
• Est. completion date: September 30, 2022

Study information

• Verified date: February 2022
• Source: Sanjay Gandhi Postgraduate Institute of Medical Sciences
• Contact: Vishvak Chanthar
• Phone: +91-9840577791
• Email: drvishvak[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: September 30, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Death
• Programmed Cell Death Ligand 1

Intervention

Other:
• Observational Study
Assessment of Prognostic and Predictive value of Tumor-Infiltrating Lymphocytes and Programmed cell Death - Ligand 1 in Breast cancer

Locations

Country	Name	City	State
India	Sanjay Gandhi Postgraduate Institute of Medical Sciences	Lucknow	Uttar Pradesh

Sponsors (1)

Lead Sponsor	Collaborator
Sanjay Gandhi Postgraduate Institute of Medical Sciences

Country where clinical trial is conducted

India, 

References & Publications (4)

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, André F, Klauschen F, Blohmer JU, Krappmann K, Schmidt M, Tesch H, Kümmel 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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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