Triple Negative Breast CancerTIL; PD1; PDL1NCT06965361
Stromal Tumor-Infiltrating Lymphocyte Levels Are Associated With Immune Checkpoint Proteins In Triple Negative Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
An observational study of Triple Negative Breast Cancer, run by Ziauddin University at 1 site in Pakistan.
Trial 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… Read more about this study
- Who is it for?
- Ages 24 to 45 years, women only
- Conditions the study is for
- Triple Negative Breast Cancer
- What is being tested?
- carboplatin
- Type of treatment
- Medical device
- How many people
- 54 participants
- Where
- 1 sitePakistan
- Study dates
- 2 Jan 2021to 31 Jul 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 45 years
- Women only
- No healthy volunteers
- Adult
Study population: Karachi subset of population
Who may be able to join
- 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
Who cannot join
- Patients who had a history of other malignant tumors
- Patients who did not complete NAC.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Triple Negative Breast Cancer
- Being tested
- carboplatin
- 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
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
carboplatinDrug
Also called Doxorubicin
carboplatin use due to its effectiveness in increasing pathological complete remission (pCR) rates and improving survival outcomes
carboplatinDevice
Also called Carpsol®
used in the treatment of triple-negative breast cancer (TNBC) due to its effectiveness in achieving pathological complete response (pCR) and breast-conserving surgery (BCS) rates.
| Study group | Role | What they receive |
|---|---|---|
| A+T group and A+T+C group | All TNBC patients included in the study received at least four cycles of NACT regimens and were classified into two groups: anthracycline-containing, taxane- (A+T group) and anthracycline/taxane/carboplatin (A+T+C group) combinations Receives: Drug: carboplatin; Device: carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stromal tumor-infiltrating lymphocyte levels are associated with immune checkpoint proteins in triple negative breast cancer patients receiving neoadjuvant chemotherapy
The TILs levels were evaluated on Hematoxylin-eosin-stained (H\&E) tissue sections as percentages and three predefined categories were used: Low TIL scores of 0-10%, intermediate 11-40% and high TIL > 40%.
Measured: From enrollment to the end of treatment received at least four cycles of NACT regimens. One cycle last for 21 days.
Secondary outcomes (1)
Evaluation of PD-1, PD-L1 and LAG-3 in triple negative breast cancer patients receiving neoadjuvant chemotherapy
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.
Measured: From enrollment to the end of treatment received at least four cycles of NACT regimens. One cycle last for 21 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2025
- Study start2 Jan 2021
- Primary completion31 Jul 2022
- Study completion31 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Triple Negative Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ziauddin University
- Sponsor type
- University, hospital or other
- Collaborators
- Jinnah Sindh Medical University
- Responsible party
- Principal investigator, Shamim Mushtaq, Ziauddin University
- Investigators
- Shamim Mushtaq, PhD, Principal investigator, Ziauddin University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06965361
- Sponsor's protocol ID
- 1730120SMBIO
- Other IDs
- 20-11952/NRPU/RGM/R&D/HEC
- Acronym
- TIL; PD1; PDL1
- Status last verified
- May 2025
- First submitted
- 23 Apr 2025
- Last updated
- 16 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 30335131
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Stromal Tumor-Infiltrating Lymphocyte Levels Are Associated With Immune Checkpoint Proteins In Triple Negative Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
- ClinicalTrials.gov ID
- NCT06965361
- Acronym / sponsor ID
- TIL; PD1; PDL1 / 1730120SMBIO
- 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
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Ziauddin UniversityUniversity, hospital or other
- Collaborators
- Jinnah Sindh Medical University
- Study start
- 2 Jan 2021 (actual)
- Primary completion
- 31 Jul 2022 (actual)
- Study completion
- 31 Jul 2022 (actual)
- First posted
- 11 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A+T group and A+T+C group | – | Drug: carboplatin, Device: carboplatinAll TNBC patients included in the study received at least four cycles of NACT regimens and were classified into two groups: anthracycline-containing, taxane- (A+T group) and anthracycline/taxane/carboplatin (A+T+C group) combinations |
Who may qualify
- Ages
- 24 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Karachi subset of population
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- Patients who had a history of other malignant tumors
- Patients who did not complete NAC.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| carboplatinAlso: Doxorubicincarboplatin use due to its effectiveness in increasing pathological complete remission (pCR) rates and improving survival outcomes | Drug | A+T group and A+T+C group |
| carboplatinAlso: Carpsol®used in the treatment of triple-negative breast cancer (TNBC) due to its effectiveness in achieving pathological complete response (pCR) and breast-conserving surgery (BCS) rates. | Device | A+T group and A+T+C group |
Primary outcome
Stromal tumor-infiltrating lymphocyte levels are associated with immune checkpoint proteins in triple negative breast cancer patients receiving neoadjuvant chemotherapy
Time frame: From enrollment to the end of treatment received at least four cycles of NACT regimens. One cycle last for 21 days.
The TILs levels were evaluated on Hematoxylin-eosin-stained (H\&E) tissue sections as percentages and three predefined categories were used: Low TIL scores of 0-10%, intermediate 11-40% and high TIL > 40%.
1 secondary outcome
Evaluation of PD-1, PD-L1 and LAG-3 in triple negative breast cancer patients receiving neoadjuvant chemotherapy
Time frame: From enrollment to the end of treatment received at least four cycles of NACT regimens. One cycle last for 21 days.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2025.
- Background: PubMed 30335131Loibl 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.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Triple Negative Breast Cancer
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
Active, not recruitingPhase 1/2
Phase I/II Study of the Anti-Programmed Death Ligand-1 Durvalumab Antibody (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Can...
Colorectal Neoplasms, Breast Neoplasms
RecruitingPhase 2
Study of Patritumab Deruxtecan Plus Pembrolizumab With Other Anticancer Agents in Participants With High-Risk Early-Stage Triple-Negative or Hormone Receptor-Low Positive/HER-2 Negative Breast Cancer (MK-1022-010, HERTHENA-Breast-03)
Breast Neoplasms, Breast Cancer
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shamim Mushtaq, PhD principal investigator
Ziauddin University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Triple Negative Breast Cancer, run by Ziauddin University at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stromal tumor-infiltrating lymphocyte levels are associated with immune checkpoint proteins in triple negative breast cancer patients receiving neoadjuvant chemotherapy (time frame: From enrollment to the end of treatment received at least four cycles of NACT regimens. One cycle last for 21 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06965361, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2025.