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Programmed Death Ligand 1 (PDL1) Expression in Neoadjuvant Triple-Negative Breast Cancer: Association With
Atif Ali Hashmi1,2, Noreen Wahid1, Ghazala Mudassir3
1Department of Histopathology, Liaquat National Hospital and Medical College, Karachi, Pakistan.
Background:
Programmed death ligand 1 (PDL1) expression in tumors is linked to immune evasion in various cancers, making these patients potential candidates for PDL1 inhibitors. Although immune checkpoint blockade therapy has gained approval for breast cancer treatment, especially triple-negative breast cancer (TNBC), there is a lack of PDL1 expression data in Pakistani breast cancer patients. In our study, PDL1 expression was assessed in TNBC to determine eligibility for PDL1 inhibitors. Our study aimed to evaluate the frequency of PDL1 expression in TNBC. We also examined how PDL1 expression correlates with clinicopathological characteristics and prognostic factors in patients with TNBC. Moreover, the association of neoadjuvant chemotherapy response with PDL1 expression was also evaluated.
Methods:
This cross-sectional study was conducted at the Liaquat National Hospital Histopathology Department from January 2022 to June 2023. A total of 128 biopsy-proven cases of TNBCs were administered neoadjuvant chemotherapy before surgery during this period. PDL1 immunohistochemical staining was performed on prechemotherapy needle biopsies. Expression was determined using the combined positive score (CPS). CPS is the number of PDL1-stained cells (tumor cells, lymphocytes, and macrophages) divided by the total number of viable tumor cells multiplied by 100. Cases with CPS ≥ 10 were considered PDL1-positive.
Results:
Complete pathological response (pCR) was observed in 32.8% (n = 42) of cases. PDL1 expression was observed in 18.8% (n = 24) of cases. The majority of cases showed a high residual cancer burden (RCB-III) (n = 53, 41.4%). A significant association was noted between PDL1 expression and neoadjuvant chemotherapy response (p < 0.01). PDL1-positive cases had a higher pCR (n = 16, 66.7%) than PDL1-negative cases (n = 26, 25%). PDL1-positive cases showed a lower frequency of RCB-II-III (RCB-II: 8.3%; RCB-III: 0%) than PDL1-negative cases (RCB-II: 25%; RCB-III: 51%), with a significant p value (p < 0.01).
Conclusion:
Overall, PDL1 expression was low in TNBC cases in our study; however, identifying these cases is important to identify those that can benefit from immunotherapy. We found a significant association of PDL1 expression with neoadjuvant chemotherapy response and RCB. Moreover, PDL1 positivity was associated with lower Ki67 index and older age. Therefore, we recommend routine PDL1 testing in all cases of TNBC to predict neoadjuvant chemotherapy response.
Insights
Programmed death ligand 1 (PDL1) expression is low in Pakistani triple-negative breast cancer (TNBC) but predicts immunotherapy response. Routine PDL1 testing in TNBC can help identify patients who may benefit from PDL1 inhibitors.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Programmed death ligand 1 (PDL1) expression is a biomarker for immune evasion and a predictor of response to PDL1 inhibitors in various cancers.
- Triple-negative breast cancer (TNBC) is a subtype of breast cancer that often lacks targeted therapies, making immune checkpoint inhibitors a potential treatment option.
- Limited data exists on PDL1 expression in Pakistani breast cancer patients, highlighting the need for local studies.
Purpose of the Study:
- To evaluate the frequency of PDL1 expression in TNBC patients in Pakistan.
- To determine the correlation between PDL1 expression and clinicopathological characteristics and prognostic factors in TNBC.
- To assess the association between PDL1 expression and response to neoadjuvant chemotherapy in TNBC.
Main Methods:
- A cross-sectional study was conducted on 128 biopsy-proven TNBC cases treated with neoadjuvant chemotherapy.
- PDL1 immunohistochemical staining was performed on pre-chemotherapy needle biopsies.
- PDL1 expression was quantified using the combined positive score (CPS), with CPS ≥10 considered PDL1-positive.
Main Results:
- PDL1 expression was observed in 18.8% of TNBC cases.
- A significant association was found between PDL1 expression and neoadjuvant chemotherapy response (p < 0.01).
- PDL1-positive cases exhibited a higher pathological complete response (pCR) rate (66.7%) compared to PDL1-negative cases (25%) and a lower frequency of high residual cancer burden (RCB-II/III).
Conclusions:
- PDL1 expression is relatively low in Pakistani TNBC patients but is significantly associated with a better response to neoadjuvant chemotherapy.
- PDL1 positivity correlates with lower Ki67 index and older age.
- Routine PDL1 testing in TNBC is recommended to predict neoadjuvant chemotherapy response and identify patients eligible for immunotherapy.
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