A review of the racial heterogeneity of breast cancer stem cells.

Breast Cancer Stem Cells has become the toast of many breast cancer investigators in the past two decades owing to their crucial roles in tumourigenesis, progression, differentiation, survival and chemoresistance. Despite the growing list of research data in this field, racial or ethnic comparison studies on these stem cells remain scanty. This study is a comparative racial analysis of putative breast cancer stem cells. Research articles on the clinicopathological significance of breast cancer stem cells within a period of 17 years (2003-2020) were reviewed across 5 major races (African/Black American, Asian, Caucasian/White, Hispanic/Latino, and American). The associations between the stem cells markers (CD44+/CD24-/low, BMI1, ALDH1, CD133, and GD2) and clinicopathological and clinical outcomes were analysed. A total of 40 studies were included in this study with 50% Asian, 25% Caucasian, 10% African, 5% American and 2.5% Hispanic/Latino, and 7.5% other mixed races. CD44+/CD24-/low has been associated with TNBC/Basal like phenotype across all races. It is generally associated with poor clinicopathological features such as age, tumour size, lymph node metastasis and lymphovascular invasion. In Asians, CD44+/CD24-/low was associated with DFS and OS but not in Caucasians. ALDH1 was the most studied breast CSC marker (40% of all studies on breast cancer stem cell markers) also associated with poor clinicopathological features including size, age, stage, lymph node metastasis and Nottingham Prognostic Index. ALDH1 was also associated with DFS and OS in Asians but not Caucasians. Racial variations exist in breast cancer stem cell pattern and functions but ill-defined due to multiple factors. Further research is required to better understand the role of breast CSC.

The role of ALDH1A1 in contributing to breast tumour aggressiveness: A study conducted in an African population.

Aldehyde dehydrogenase 1 member A1 (ALDH1A1) is one of the most well studied breast cancer stem cells. Its expression has been associated with poor clinicopathological features and clinical outcomes in several studies. This paper studies the expression of ALDH1A1 and its combination with CD44+/CD24-/low breast cancer stem cell and their association with clinicopathological parameters and molecular subtypes. METHOD: Tissue Microarray was constructed from 222 Formalin Fixed Paraffin Embedded (FFPE) breast cancer tissues. The expression of ALDH1A1, CD44 and CD24 were assessed by Immunohistochemistry (IHC). The association of ALDH1A1 and its association with clinicopathological parameters, molecular subtypes, CD44 and CD24 were studied in an African population. The association between CD44+/CD24-/low/ALDH1+ and the clinicopathological phenotypes were also studied. RESULTS: A high ALDH1A1 expression of 90% was recorded in this study. No association was found between ALDH1A1 and clinicopathological parameters. ALDH1A1 was positively associated with CD24 (r = 0.228, OR-4.599 95% CI- 1.751-12.076, p = 0.001) and CD44 (r = 0.228, OR-5.538 95%CI- 1.841-16.662, p = 0.001) but not associated with CD44+/CD24-/low (r = 0.134, OR- 2.720 95%CI- 0.959-7.710, p = 0.052). CD44+/CD24-/ALDH1+ however had significant associations with Age (p- 0.020, r = 0.161, OR- 2.771, 95%CI 1.147-6.697), Gender (p = 0.004, OR- 15.333 95%CI 1.339-175.54), Tumour grade (p = 0.005, r = 0.197, OR-3.913 95%CI 1.421-10.776) and clinical prognostic staging (p = 0.014, r = 0.182, OR-3.028 95%CI- 1.217-7.536). There was no association between CD44+/CD24-/ALDH1+ and the molecular subtypes. CONCLUSION: The high expression of ALDH1A1 in breast cancer makes it an important target for targeted therapy. This study further confirms the increased tumourigenicity of CD44+/CD24-/ALDH1+ combination phenotype and its association with increased tumour grade and clinical prognostic stage. Survival studies of ALDH1A1 and other breast cancer stem cells in African populations are strongly recommended to help further understand their effect on tumour aggressiveness.