Cancer stem cell markers, chemotherapy response, and survival in triple-negative breast cancer

doi:10.5306/wjco.v17.i2.116251

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World Journal of Clinical Oncology

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Retrospective Cohort Study

World J Clin Oncol. Feb 24, 2026; 17(2): 116251
Published online Feb 24, 2026. doi: 10.5306/wjco.v17.i2.116251

Cancer stem cell markers, chemotherapy response, and survival in triple-negative breast cancer

Faisal Nabi Depar, Ahmed Jamal Chaudhary, Jawad Hameed, Faisal Sarwar Abbasi, Bibi Uzma, Amjad Ali, Naheed Akhtar, Rizwan Khan, Afsheen Siddiqi, Sohail Riaz

Faisal Nabi Depar, Department of Medicine, People’s University of Medical and Health Sciences for Women, Nawabshah 67480, Sindh, Pakistan

Ahmed Jamal Chaudhary, Department of Medicine, Lahore Medical and Dental College, Lahore 54000, Punjab, Pakistan

Jawad Hameed, Anesthesia and Critical Care, Lady Reading Hospital MTI, Peshawar 44230, Khyber Pakhtunkhwa, Pakistan

Faisal Sarwar Abbasi, Department of Medicine, Abbasi Shaheed Hospital, Karachi 75300, Sindh, Pakistan

Bibi Uzma, Department of Genetic Engineering, IBGE Institute of Biotechnology and Genetic Engineering, Agriculture University Peshawar, Peshawar 25130, Khyber Pakhtunkhwa, Pakistan

Amjad Ali, Department of Clinical Oncology, Life Care Hospital and Research Center, Peshawar 25100, Khyber Pakhtunkhwa, Pakistan

Naheed Akhtar, Institute of Radiotherapy and Nuclear Medicine Hospital, Peshawar 25000, Khyber Pakhtunkhwa, Pakistan

Rizwan Khan, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China

Afsheen Siddiqi, Department of Pharmacology, Ayub Medical College, Abbottabad 22040, Khyber Pakhtunkhwa, Pakistan

Sohail Riaz, Department of Medicine, International University of Kyrgyzstan, International School of Medicine, Bishkek 720054, Kyrgyzstan

Author contributions: Depar FN, Chaudhary AJ, Hameed J, Abbasi FS, Uzma B, Ali A, Akhtar N, Siddiqi A, and Khan R collected and assembled the data; Riaz S designed the research study, analyzed the data and wrote the manuscript; and all authors have read and approved the final manuscript.

Institutional review board statement: This study was approved by the Medical Ethics Committee of Institute of Radiotherapy and Nuclear Medicine, approval No. IRNUM-IRB-2023-045.

Informed consent statement: Informed consent was waived due to the retrospective nature of the study.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.

Data sharing statement: Data are available from the corresponding author upon reasonable request.

Corresponding author: Sohail Riaz, MD, Department of Medicine, International University of Kyrgyzstan, International School of Medicine, 6 Seven April Street, Bishkek 720054, Kyrgyzstan. sohailriaz552@gmail.com

Received: November 6, 2025
Revised: December 11, 2025
Accepted: January 14, 2026
Published online: February 24, 2026
Processing time: 92 Days and 14.8 Hours

Abstract

BACKGROUND

Triple-negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options, primarily relying on chemotherapy, yet often leading to recurrence due to chemoresistance. Cancer stem cells (CSCs) contribute to tumor heterogeneity, resistance, and poor prognosis, but data in Pakistani populations are scarce. This study hypothesizes that a positive CSC phenotype independently predicts reduced pathological complete response (pCR) and inferior survival outcomes.

AIM

To investigate CSC markers’ association with chemotherapy response and survival in Pakistani TNBC patients.

METHODS

Retrospective cohort study at Institute of Radiotherapy and Nuclear Medicine, Peshawar, Pakistan, including 256 women with TNBC from January 2015 to December 2022. CSC markers (CD44 high, CD24 low, aldehyde dehydrogenase 1 positive) were assessed via immunohistochemistry on pre-treatment biopsies. Outcomes: pCR to neoadjuvant chemotherapy, overall survival, disease-free survival. Data were analyzed with multivariable logistic regression and Cox proportional hazards models, adjusting for age, tumor grade, and stage.

RESULTS

The CSC-positive phenotype was identified in 26 patients (10.2%). Compared to negative cases, positive cases had lower pCR rates [5.0% vs 51.8%; adjusted odds ratio = 0.05, 95% confidence interval (CI): 0.01-0.39, P = 0.004]. The positive phenotype was associated with poorer overall survival (adjusted hazard ratio = 4.35, 95%CI: 2.43-7.79, P < 0.001), with a median overall survival of 19 months vs 27 months. No association with disease-free survival was observed (hazard ratio = 0.86, 95%CI: 0.43-1.73, P = 0.675).

CONCLUSION

CSC markers are associated with reduced chemotherapy response and inferior overall survival in Pakistani TNBC patients. These findings suggest their potential as prognostic biomarkers and highlight the need for future research into targeted strategies, such as proteomic profiling and Proteolysis Targeting Chimeras technology, to overcome chemoresistance in this population.

Keywords: Triple-negative breast cancer; Cancer stem cells; CD44; CD24; Aldehyde dehydrogenase 1; Chemotherapy response; Survival; Pakistan

Core Tip: In a Pakistani triple-negative breast cancer cohort, the cancer stem cell phenotype (CD44 high/CD24 low/aldehyde dehydrogenase 1 positive) occurred in 10.2% of cases and independently predicted markedly lower pathological complete response (5.0% vs 51.8%) and shorter overall survival (hazard ratio = 4.35). These findings from a South Asian population with high triple-negative breast cancer burden support cancer stem cell marker integration into risk stratification for personalized therapy in resource-limited settings.