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

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.

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

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.

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).

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.