Clinical trial NCT06965361: Stromal Tumor-Infiltrating Lymphocyte Levels Are Associated With Immune Checkpoint Proteins In Triple Negative Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
Official title: Stromal Tumor-Infiltrating Lymphocyte Levels Are Associated With Immune Checkpoint Proteins In Triple Negative Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Triple Negative Breast Cancer
Keywords: carboplatin-based NACT regimen
tumor-infiltrating lymphocytes
Programmed cell death-1
Programmed cell death Ligand-1
lymphocyte activation gene-3
Triple-negative breast cancer
Lead sponsor: Ziauddin University
Sponsor class: OTHER
Collaborators: name: Jinnah Sindh Medical University
First posted: 2025-05-11
Enrollment: 54
Sex: FEMALE
Minimum age (years): 24
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Karachi subset of population

Brief summary: The goal of this observational study is to learn about the effects of neoadjuvant chemotherapy (NACT) anthracycline-containing, taxane- (Intervention A +T) and anthracycline/taxane /carboplatin (Intervention A+T+C) treatment in young (age; 24-45 years) Triple Negative Breast Cancer (TNBC) female Patients by evaluating Stromal tumor-infiltrating lymphocytes (TILs) Programmed cell death-1 (PD-1), its ligand (PD-L1) and lymphocyte activation gene-3 (LAG-3) checkpoint proteins within tumor.

The main question it aims to answer is:

Does TILs are the most reliable immune markers and are significantly associated with PD-1, PD-L1 and LAG-3 in carboplatin based NACT treated (Intervention A+T+C) group of TNBC patients? Participants (TNBC Patients) already taking intervention A+T and A+T+C as part of their regular medical care for TNBC.

Detailed description: Stromal tumor-infiltrating lymphocytes (TILs) are currently being considered as a prognostic factor in triple-negative breast cancer (TNBC) and their association with the tumor immune microenvironment is less clear. To address this knowledge gap, investigators aimed to evaluate the expression and association of Programmed cell death-1 (PD-1), its ligand (PD-L1) and lymphocyte activation gene-3 (LAG-3) checkpoint proteins with TILs in neoadjuvant chemotherapy (NACT) treated TNBC patients.

Patients (n=54; aged;24-45 years) were classified into two groups: thirty-nine received anthracycline-containing, taxane- (A+T group) and fifteen received anthracycline/taxane /carboplatin (A+T+C group) in combinations. Immunohistochemistry (IHC) staining was used for the evaluation of PD-1, PD-L1 and LAG-3. However, TIL assessment was done by hematoxylin and eosin (H\&E)-staining in TNBC patient's biopsies who received NACT.

Eligibility criteria: Inclusion Criteria:

* Female (aged 24-45 years) TNBC patients
* Diagnosed TNBC Patients with immunohistochemistry (IHC) negative test for estrogen receptor (ER), progesterone receptor (PR), and HER-2
* Patients with and without metastases

Exclusion Criteria:

* Patients who had a history of other malignant tumors
* Patients who did not complete NAC.

Primary outcomes:
measure: Stromal tumor-infiltrating lymphocyte levels are associated with immune checkpoint proteins in triple negative breast cancer patients receiving neoadjuvant chemotherapy
timeFrame: From enrollment to the end of treatment received at least four cycles of NACT regimens. One cycle last for 21 days.
Secondary outcomes:
measure: Evaluation of PD-1, PD-L1 and LAG-3 in triple negative breast cancer patients receiving neoadjuvant chemotherapy
timeFrame: From enrollment to the end of treatment received at least four cycles of NACT regimens. One cycle last for 21 days.
Other outcomes:
Locations:
city: Karachi
country: Pakistan
facility: Shamim
state: Sindh
Study officials:
affiliation: Ziauddin University
name: Shamim Mushtaq, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Loibl S, Weber KE, Timms KM, Elkin EP, Hahnen E, Fasching PA, Lederer B, Denkert C, Schneeweiss A, Braun S, Salat CT, Rezai M, Blohmer JU, Zahm DM, Jackisch C, Gerber B, Klare P, Kummel S, Schem C, Paepke S, Schmutzler R, Rhiem K, Penn S, Reid J, Nekljudova V, Hartman AR, von Minckwitz G, Untch M. Survival analysis of carboplatin added to an anthracycline/taxane-based neoadjuvant chemotherapy and HRD score as predictor of response-final results from GeparSixto. Ann Oncol. 2018 Dec 1;29(12):2341-2347. doi: 10.1093/annonc/mdy460.