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Strong tumor expression of ALDH1A1 is 
associated with Black race, metabolic 
disorders, and poor breast cancer outcomes 
Steficah Maosa1,2, Lisa Frerichs1, Scott D. Siegel, 1Zachary Schug3, Jennifer Sims-Mourtada1 

1Cawley Center for Translational Cancer Research, Helen F Graham Cancer Center and Research Institute, 
Christiana Care Health Services, Inc. Newark, USA 
2Department of Biological Sciences, The University of Delaware, Newark, DE, USA 
3The Wistar Institute, Philadelphia, Pennsylvania, USA 

*Corresponding author: Jennifer Sims-Mourtada, email: jsimsmourtada@chrisitanacare.org 

ABSTRACT 
Racial differences in tumor biology may explain worse breast cancer outcomes in Black women relative 
to White women. This study provides a comparative racial analysis in Black and White women in terms of 
Aldehyde dehydrogenase1 member A1 (ALDH1A1) expression and its association to clinicopathological 
features. Expression of ALDH1A1 in both tumor and stromal cells was assessed by immunohistochemistry 
in tissue microarrays containing 253 breast tumors including 161 tumors from White patients and 92 from 
Black patients. Relationships to clinicopathological features for strong and moderate to low ALDH1A1 
staining were determined using Pearson’s Chi Square and an odds ratio was determined. Survival and 
recurrence were analyzed using Kaplan-Meier curves and Mantel Log-Rank tests. Multivariate analysis 
was conducted using Cox-proportional hazards tests. Black, obese, and diabetic women showed higher 
staining intensity in both tumor and stromal tissue. Strong tumor staining was associated with Black race, 
advanced stage, high grade obesity and diabetes. Strong stromal expression was associated with estrogen 
receptor positivity, and prediabetes/diabetes. Patients with strong tumor ALDH1A1 had shorter recurrence 
free and overall survival compared to those with moderate to low expression. When stratified by race, 
Black women with strong tumor ALDH1A1 expression had shorter recurrence free survival compared to 
White women. Strong tumor ALDH1A1 staining was an independent predictor of poor overall survival in 
both Black and White women. These findings indicate that ALDH1A1 expression is associated with poor 
outcomes in breast cancer, particularly in Black women, and provide the first link between tumor ALDH1A1 
expression, obesity, and diabetes. 

KEYWORDS: Breast cancer; ALDH1A1, Black women, metabolic disorders, obesity. 

Citation: Maosa S et al (2023) Strong tumor expression of ALDH1A1 is associated with Black race, metabolic 
disorders, and poor breast cancer outcomes. Cancer Health Disparities 7:e1-14, doi:10.9777/chd.2023.1003  
  



 
 
 
 
 

 
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Introduction 
Breast cancer accounts for a third of all cancers 
diagnosed in Black women and is the leading cause 
of cancer death in this population (Giaquinto et al., 
2022). Although incidence rates are comparable, 
Black women are 41% more likely to die of breast 
cancer than White women and are twice as likely to 
be diagnosed with aggressive breast cancers such 
as triple negative or inflammatory breast cancers 
(Giaquinto et al., 2022; Stringer-Reasor et al., 2021). 
Higher mortality rates in Black women are 
attributable to many factors including later stage of 
diagnosis, limited access to high quality care, 
unfavorable tumor characteristics, and increased 
prevalence of obesity and associated comorbidities 
(Stringer-Reasor et al., 2021). Studies examining 
mortality rates in Black and White women 
diagnosed with early stage breast cancer show that 
after controlling for non-biological factors such as 
socioeconomic status, treatment factors and tumor 
stage at diagnosis, Black women still had higher 
mortality rates than White women (Dietze et al., 
2015; Hershman et al., 2005; Jatoi et al., 2003; Silber 
et al., 2013). These findings indicate that racial 
molecular and genetic differences in tumor biology 
may play a role in poor survival rates among Black 
women. However, racial differences in tumor 
biology and their interaction with other biological 
and non-biological risk factors are poorly 
understood. 

Aldehyde dehydrogenases are detoxifying enzymes 
that play a critical role in metabolism of intracellular 
aldehydes. In particular, the ALDH1 family has been 
implicated in the oxidation of retinol to retinoic acid 
which impacts differentiation state, treatment 
resistance, and anti-tumor immune responses(Ayub 
et al., 2015; Bazewicz et al., 2019; Ginestier et al., 
2007). Strong ALDH1 expressing cells are thought 
to be tumor initiating cells and are associated with 
other stem-cell markers and poor outcomes in 

breast cancer (Ginestier et al., 2007). In triple 
negative breast cancer, ALDH1 expression was 
significantly correlated with larger tumor size, later 
stage and is an independent prognostic factor(Ma 
et al., 2017). Strong ALDH1 expression has been 
observed in breast cancers of Black women and is 
associated with basal like features in this population 
(Nalwoga et al., 2010). 

The ALDH1 family is made up of several isoforms, 
with ALDH1A1 and ALDH1A3 being the most 
important for breast cancer progression and 
resistance (Marcato et al., 2011b). Although both are 
involved in the biosynthesis of retinoic acid, 
ALDH1A1 has a broader role in the metabolism of 
intracellular and extracellular aldehydes 
(Poturnajova et al., 2021). While our group and 
others have shown that ALDH1A3 expression 
correlates with prognosis, the role of ALDH1A1 has 
been controversial and may be dependent on cut-
off levels used to score high and low (Althobiti et 
al., 2020; Opdenaker et al., 2014; Sjostrom et al., 
2015). Strong mRNA expression of ALDH1A1 has 
been associated with good prognosis in triple 
negative breast cancer (Liu et al., 2015). However, at 
the protein level, strong expression in tumor cells 
was associated with stage, triple negativity, and 
poor response to neoadjuvant 
chemotherapy(Khoury et al., 2012), as well as worse 
prognosis (Sjostrom et al., 2015). A recent study 
examining expression of ALDH1A1 in 222 breast 
cancers from Ghanian women reported tumor 
expression in 90% of tumors. Although no 
association with clinicopathologic features was 
observed with ALDH1A1 alone, significant 
associations with tumor stage and grade were 
observed in tumors with a large stem-like 
population indicated by strong staining of ALDH1A1 
and CD44 and weak CD24 expression (Gyan et al., 
2021). Outcome analysis was not performed in this 
study. 



 
 
 
 
 

 
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In addition to its possible role in breast cancer 
progression, expression of ALDH1A1 has been 
linked to lipogenic adipogenesis, accumulation of 
visceral fat (Reichert et al., 2011; Yasmeen et al., 
2013), and altered glucose tolerance (Petrosino et 
al., 2014) in ALDH1A1 knock-out mouse models. 
Additionally, ALDH1A1 expression in adipose tissue 
in both mice and humans is induced by a high-fat 
diet (Landrier et al., 2017). Pharmacological 
inhibition of ALDH1A1 suppressed weight gain in a 
mouse model of diet-induced obesity and reduced 
genes involved in fatty acid synthesis in multiple 
tissues (Haenisch et al., 2018). As obesity is strongly 
associated with breast cancer risk and outcomes, 
particularly in Black women (Dietze et al., 2018; 
Micaily et al., 2021), we sought to investigate the 
relationship between ALDH1A1 expression, 
metabolic disorders and breast cancer outcomes in 
Black women compared to White women. 

Methods 
Patient samples and data 
Paraffin embedded blocks of breast cancer tissue 
were obtained from the biorepository at the Helen 
F. Graham Cancer Center and Research Institute 
(HFGCCRI) under a protocol approved by the 
institutional review board of ChristianaCare, 
Newark, Delaware. Blocks were obtained from 
patients undergoing surgical resection from years 
2007-2011 and were pathologically confirmed as 
invasive breast cancer tissue. Paraffin tissues were 
constructed into 4x5 tissue microarrays (TMA) with 
a 5 mm core size and cut as serial sections. 
Clinicopathologic data was taken from patient 
charts. Patients pathologic stage of IIA or stronger 
were considered to have advanced breast cancer, 
consistent with a recent recommendation from the 
Breast Cancer Surveillance study that found that this 
definition most accurately predicts 5 year survival 
(Kerlikowske et al., 2021). Obesity was determined 
by BMI at diagnosis. Patients were coded as obese 

if their BMI was greater than or equal to 30. Data 
regarding other co-morbidities such as blood 
glucose levels (normal or high (prediabetes) or a 
clinical diagnosis of diabetes mellitus at the time 
breast cancer occurrence was available in the 
biorepository database for a subset of patients 
n=130. 

Immunohistochemical procedure 
Paraffin-embedded slides were deparaffinized and 
rehydrated, and heat antigen epitope retrieval was 
performed for 16 hours at 60°C. Slides were stained 
using a 1:100 dilution of ALDH1A1 antibody (Kiefer 
et al., 2012) (Abcam, clone EP1933Y) using the 
Mouse and Rabbit Specific HRP/AEC (ABC) 
Detection IHC Kit (Abcam, ab93705), following the 
manufacturer’s instructions. Negative control slides 
were performed with the omission of antibody. 
Slides were counterstained with hematoxylin. 
Images were captured using a Zeiss Axio 
microscope using a 10X objective. Segmentation of 
tumor and stromal cells and measurement of sum 
intensity per area was performed using Zen Blue. 

Statistical analysis 
Statistical analysis was done in graph pad PRISM 8 
and IBM27 SPSS. Comparisons of staining intensity 
were done using student’s T tests. Staining 
intensities were divided into quartiles, with the top 
quartile considered to be strong ALDH1A1 
expression. Relationships for strong and moderate 
to low expressing slides were determined using 
Pearson’s Chi Square and an odds ratio was 
determined. Survival and recurrence were analyzed 
using Kaplan-Meier curves and Mantel Log-Rank 
tests. Multivariate analysis was conducted using 
Cox-proportional hazards tests. 

Results 
Patient Characteristics 
This study was comprised of a cohort of 253 
patients with invasive ductal carcinoma, including 



 
 
 
 
 

 
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161 White patients and 92 Black patients. Patient 
demographics and clinicopathologic characteristics 
are summarized in Table 1. HER2 receptor status 
was not known for all patients and was not included 
in this analysis. Black patients were significantly 

more likely to have advanced stage (p=0.022) and 
have a BMI greater than 30 at diagnosis (p=0.013). 
No significant racial differences were observed in 
tumor grade and expression of hormone receptors 
in this cohort. 

 

Table 1. Comparison of patient characteristics between White and Black Patients. 

Patient characteristics All White Black p value 

 number % number % number %  

Samples 253 100 161 63.6 92 36.4  

Stage 

Early Stage 156 61.7 108 67.1 48 52.2 0.022* 

Advanced  97 38.3 53 32.9 44 47.8  

Grade 

low-medium 74 29.2 54 33.5 23 25 0.164 

high 179 70.8 110 68.3 69 75  

Hormone receptor expression 

HR+ 75 29.6 47 29.2 28 30.4 0.887 

HR- 178 70.4 114 70.8 64 69.6  

Obesity 

non-obese 131 51.8 93 57.8 38 41.3 0.013* 

obese 122 48.2 68 42.2 54 58.7  

Diabetes 

normal blood glucose 99 76.10% 67 79.8 32 69.5 0.204 

pre-diabetes/diabetes 31 23.80% 17 20.1 14 30.4  

 
Strong tumor ALDH1A1 staining is associated 
with race, stage, obesity, and diabetes. 
Tumor microarrays were constructed from paraffin 
embedded surgical sections and stained with an 
anti-ALDH1A1 specific antibody. Tumor and stromal 
staining were quantified as sum intensity per area. 
Figure 1 shows representative samples with strong 
and low tumor and stromal staining. Significantly 
stronger staining intensities were observed in tumor 
tissue from Black women, obese women, and 

women with prediabetes/ diabetes (Figure 2A, 2C 
and 2E). Similarly, significantly stronger staining 
intensities of ALDH1A1 were found in stroma of 
tumors from Black women and women who were 
obese or had prediabetes or diabetes (Figure 2B, 
2D and 2F). Strong tumor staining (specimens that 
were in the highest quartile) was associated with 
Black race (OR 1.625, CI 1.202-2.270, p=.004), 
advanced stage (OR 1.454, CI 1.062-1.991, p=.037), 
strong grade (OR 1.209, CI 1.036-1.441, p=.039), 



 
 
 
 
 

 
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obesity (OR 1.441, CI 1.122-1.825, p=0.009) and 
diabetes (OR 1.599, CI 1.206-2.119, p=.001). 
Although Black women in our cohort were more 
likely to be obese and have advance cancer, the 
association with race remained even when 
controlling for stage (Chi square 3.414, p=0.036) 
and obesity (Chi square 3.328, p= 0.038). Strong 
stromal expression was associated with Black race 

(OR 1.216, CI 0.843-1.624), estrogen receptor 
positivity (OR 1.47, CI 0.996-2.190, p=0.004), obesity 
(OR 1.287, CI 1.008-1.643, p=0.044), and 
prediabetes/diabetes (OR 1.290, CI 0.970-1.1716, 
p=.038). No associations between race, stage and 
grade were observed with strong stromal staining. 
(Table 2). 

 

 

Figure 1. Immunohistochemical analysis of ALDH1A1. 
Tumor sections showing strong (top quartile by staining intensity/area) and low/moderate (lower quartiles 
by staining intensity/area) tumor and stromal expression of ALDH1A1 (red stain). Nuclei were counterstained 
with hematoxylin (blue). Images in panels were taken with a 10X objective. Images in inserts were taken with 
40X objective. 

 



 
 
 
 
 

 
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Figure 2. Differential tumor and stromal expression of ALDH1A1. 
Expression of ALDH1A1 expression in white vs black tumor (A.) and Stroma (B.), non-obese vs obese tumor 
(C.) and stroma (D.), and Non-diabetic vs prediabetic/Diabetic tumors (E.) and stroma (F.) Data is reported 
as sum red intensity per area. Solid red lines represent quartiles, dotted red line represents mean. **** 
p<.0001; *** p<.001; * p<.05. 

Table 2. Association of ALDH1A1 strong tumor and stromal expression with patient and tumor characteristics. 

Strong expression 
of ALDH1A1 Tumor expression Stromal Expression 

    OR 95% CI p value   OR 95% CI p value 

Race 
Black 1.625 1.202-2.270 0.004** Black 1.216 0.843-1.624 0.156 

White 0.704 0.537-0.923   White 0.973 0.702-1.348   

Stage 
Non-
advanced 0.762 0.584-0.994 0.037* 

Non-
advanced 1.087 0.893-1.321 0.439 

Advanced 1.454 1.062-1.991   Advanced 0.875 0.640-1.197   

Grade 
low-medium 0.572 0.330-03990 0.039* low-medium 1.222 0.829-1.802 0.325 

high 1.209 1.036-1.411   high 0.921 0.786-1.079   

Estrogen 
receptor 
expression 

ER+ 0.886 0.546-1.372 0.324 ER+ 1.472 0.996-2.190 .004** 

ER- 1.06 0.889-1.262   ER- 0.851 0.725-1.970   

Obesity 
Non-obese 0.669 0.471-0.940 0.009** Non-obese 0.764 0.591-0.989 .044* 

Obese 1.441 1.122-1.825   Obese 1.287 1.008-1.643   

Prediabetes/ 
Diabetes 

Normal 
blood glucose 0.281 0.148-0.534 0.001** 

Normal blood 
glucose 0.517 0.283-0.944 .038* 

Pre-diabetes/ 
diabetes 

1.599 1.206-2.119   Pre-diabetes/ 
diabetes 

1.29 0.970-1.716   



 
 
 
 
 

 
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Strong tumor and stromal ALDH1A1 staining 
are associated with poor outcomes 
To assess the role of strong tumor and stromal 
ALDH1A1 in breast cancer outcomes, Kaplan-Meyer 
analysis was conducted. Shorter recurrence free 
survival (RFS, p<0.001) and overall survival (OS, 
p<0.001) were observed in women whose tumors 
had strong expression of ALDH compared to those 
with moderate to low expression (Figure 3A & B). 

Interestingly, of those in the top quartile, Black 
women had worse RFS compared to White women 
(p=0.011, Figure 4A.). No racial differences were 
observed in RFS between women with moderate to 
low tumor expression of ALDH1A1 (Figure 4B.). Race 
had no effect on overall survival in either expression 
groups (Figure 4C&D) as shorter OS was observed 
in both Black and White women with strong ALDH 
expression. 

 

Figure 3. Tumor ALDH1A1 expression is associated with breast cancer outcomes. 
Kaplan-Meier survival curves showing shorter recurrence free survival (A.) and overall survival (B.) in 
patients with high expression of ALDH1A1 (top quartile). Black tick marks represent censured patients. A 
sample was considered to have strong staining if its staining index was in the top quartile. Lower quartiles 
were considered to have low to moderate staining. 

 

Sims Mourtada, Jennifer
Figures are missing title RFS on the axis



 
 
 
 
 

 
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Figure 4. High ALDH1A1 is associated with shorter RFS in Black women compared to White women. 
(A.). When stratified by race shorter RFS is observed in black women with strong tumor (staining intensity 
in top quartile) ALDH1A1 expression compared to white women. (B.) No difference in RFS was observed 
between black and white women with moderate to low tumor expression of ALDH1A1 (staining intensity in 
lower 3 quartiles) (C.) No significant racial differences were observed in OS in women with high or (D.) low 
to moderate tumor expression of ALDH1A1. Black tick marks represent censured patients. 

Although a trend of shorter RFS and OS was 
observed in women with strong ALDH1A1 stromal 
expression compared to those with moderate to 
low stromal expression, this was not significant 
(Figure 5A.&B.). No racial differences in outcomes 
were observed between Black and White women 

with strong stromal ALDH1A1 expression (Figure 
6A.-D.). Multivariate analysis revealed that 
advanced stage, hormone receptor negativity, and 
strong tumor ALDH1A1 expression were 
independently associated with worse survival 
outcomes. (Table 3). 

 

Figure 5. Stromal ALDH1A1 expression is not significantly associated with breast cancer outcomes. 
Kaplan-Meier survival curves showing shorter recurrence free survival (A.) and overall survival (B.) in patients 
with high expression of ALDH1A1 (staining intensity in top quartile). Black tick marks represent censured 
patients. 



 
 
 
 
 

 
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Figure 6. Stromal expression is not associated with breast cancer outcomes when stratified by race. 
(A.). When stratified by race shorter RFS in black women with high stromal (staining intensity in top quartile) 
ALDH1A1 expression compared to white women. (B.) No difference in RFS was observed between black and 
white women with moderate to low stromal expression of ALDH1A1 (staining intensity in lower 3 quartiles) 
(C.) No significant racial differences were observed in OS in women with high or (D.) low to moderate stromal 
expression of ALDH1A1. Black tick marks represent censured patients. 

Discussion 
Considerable data indicates that tumor biology may 
be a contributing factor to racial disparities in breast 
cancer. Previous studies have reported increased 
expression of ALDH1A1 in tumors of women with 
African Ancestry (Jiagge et al., 2018b). Our findings 
confirm that expression of ALDH1A1 is increased in 
breast tumor tissue from Black women compared 
to those from White women. Strong tumor 
expression of ALD1A1 was associated with Black 
race, high grade, advanced cancer stage, obesity, 
and diabetes. In contrast to previous studies, we did 
not find an association of between strong tumor 

ALDH1A1 expression and estrogen receptor 
negativity. 

Although ALDH1A1 activity has been linked to 
metastatic behavior and treatment resistance 
(Croker et al., 2017), the association between tumor 
ALDH1A1 expression and survival is controversial. 
We observed poor RFS and OS in women with 
strong tumor expression of ALDH1A1. A multivariate 
analysis revealed that tumor, but not stromal, 
ALDH1A1 expression is an independently associated 
with cancer outcomes. Analyses stratified by race 
revealed worse overall survival in both Black and 
White women with strong tumor ALDH1A1 



 
 
 
 
 

 
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compared to those with moderate to low 
expression. However, among women with strong 
ALDH1A1 staining, Black women had shorter 
recurrence free survival compared to White 
women. 

Members of the ALDH1 family, including ALDH1A1. 
have been associated with stemness in normal and 
malignant breast cells (Douville et al., 2009; 
Ginestier et al., 2007; Ginestier et al., 2009; Honeth 
et al., 2014; Marcato et al., 2011a; Schwartz et al., 
2013). However, research on stemness in tumors of 
Black women is limited (Jiagge et al., 2018a). One 
study found that the overall number of cells 
expressing the stem cell markers CD44+/CD24- 
cells was elevated in tumors from Black women 
(Nakshatri et al., 2015). This study also found that 
Black but not White tumors contained a distinct 
population of CD44+/CD24- cells that showed 
differential gene expression which was like that of 
mammary stem cells and included upregulation of 
TGFβ/Wnt and CTNBB1/NF-κB pathways and 
downregulation of the p53 and ER pathway. 
Additionally, Gyan et al found that expression of the 
CD44+CD24- population together with ALDH1A is 
associated with aggressive tumor characteristics 
including high tumor grade and clinical prognostic 
staging in Black women (Gyan et al., 2021). Another 
study found that tumor cells from Black women 
exhibited a cancer stem like phenotype including 
increased growth and migration compared to 
tumor cells from White women (Siddharth et al., 
2021).In this study, tumor cells from Black women 
also showed different gene expression patterns 
than those from White tumors, including elevated 
expression of stemness genes Gli-1 and Notch1. 

Stromal expression of ALDH1A1 has been 
investigated in only a few studies (Bednarz-Knoll et 
al., 2015; Sjostrom et al., 2015) which report that 
expression of ALDH1A in tumor stromal may be 
associated with improved outcomes in breast 

cancer. We found no association between strong 
stromal staining and outcomes in our study. 
However, we found that strong ALDH1A1 stromal 
expression is associated with estrogen receptor 
positivity, obesity, and diabetes. Although no 
associations between stromal staining and breast 
cancer subtypes have been reported, a positive 
association between strong stromal ALDH1A1 
expression and decreased basal markers in tumor 
cells has previously been observed (Bednarz-Knoll 
et al., 2015). Further investigation of the prognostic 
significance of ALDH1A1 stromal expression by 
breast cancer subtype is needed. 

Metabolic disorders are associated with breast 
cancer risk and outcomes, particularly in Black 
women(Jones et al., 2003; Zhao et al., 2020). 
Previous studies have shown that in addition to its 
role in stemness and oxidative stress, ALDH1A1 
plays a key role in glucose tolerance and abdominal 
fat formation (Ma et al., 2020; Petrosino et al., 2014). 
Further, increased expression of ALDH1A1 has been 
linked to accumulation of visceral fat in murine 
models and mediates inflammatory responses to a 
high-fat diet in females (Yasmeen et al., 2013). Our 
findings are the first to show an association 
between metabolic disorders and ALDH1A1 
expression in tumors. 

The mechanisms driving increased expression of 
ALDH1A1 in tumor and stroma cells, particularly in 
Black women, have yet to be fully understood. 
Functional polymorphisms in ALDH1A1 have been 
identified and studied in the context of alcohol 
dependence (Agarwal et al., 1981).The frequency of 
these alterations varies across different ethnic 
groups and several variants have strong prevalence 
among Black individuals (Crawford et al., 2014; Ji et 
al., 2019; Liu et al., 2011; Spence et al., 2003). A three 
base-pair insertion with prevalence exclusively to 
Black people was shown to increase expression of 
ALDH1A1 (Spence et al., 2003). To date, the role of 



 
 
 
 
 

 
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ALDH1A1 polymorphisms in breast cancer has not 
been well studied. Additionally, ALDH1A1 is 
regulated by factors that are also associated with 
breast cancer risk including decreased estrogen 
(Petrosino, 2014), alcohol-associated inflammation 
(Wang et al., 2017) and high fat diets (He et al., 
2020; Srinivasan et al., 2019). Moreover, we and 
other groups have shown that tumor expression of 
ALDH1A1 can be induced by activation of the IL-6-
STAT3 pathway (Arnold et al., 2020; Hellsten et al., 
2011) and may be associated with chronic 
inflammation. 

Our study has several limitations including a small 
sample size. Although our findings show that high 
ALDH1A1 expression is correlated with race and 
metabolic disorders including obesity and diabetes, 
these findings need to be confirmed in larger 
studies. We were able to obtain information on 
diabetes and blood glucose levels on a subset of 
patients; however, this information was missing in 
our biorepository database for many patients and 
warrants further study. Due to the smaller sample 
size, we were not able to further stratify patients to 
compare differences among race in prediabetes 
and diabetes groups. 

Although our analysis included stratification by 
receptor subtype, we were not able to classify 
patients according to molecular subtyping. Racial 
differences have been reported in PAM50 
molecular subtypes, with Black women having 
increased luminal B subtypes (Troester et al., 2018). 
As ALDH1A1 expression is associated to both 
luminal B and TNBC subtypes (Althobiti et al., 2020) 
this could be a confounding factor. Although our 
study investigated the association of stromal 
expression to race, comorbidities and outcomes, 
our study focused on staining index of the total 
stroma and did not determine differences by 
individual cell type. We did observe strong stromal 

staining in multiple cell types, which warrants 
further investigation. 

In conclusion, this study shows that ALDHA1A1 
expression in breast tumor and stromal cells is 
associated with Black race, obesity, and diabetes. 
When stratified by race, Black women whose 
tumors express high levels of ALDH1A1 have 
significantly shorter recurrence times than White 
women with strong ALDH1a1 expression. Moreover, 
ALDH1A1 expression was found to be an 
independent driver of outcomes. These findings 
indicate that ALDH1A1 is associated to disparities in 
breast cancer outcomes and provide the first link 
between tumor ALDH1A1 expression, obesity, and 
diabetes. Further study is needed to understand the 
mechanisms driving high ALDH1A1 expression in 
these cohorts. 

Financial support 
This work was supported by a grant from the Lisa 
Dean Mosely foundation, and by the Delaware 
INBRE program, with a grant from the National 
Institute of General Medical Sciences – NIGMS (P20 
GM103446) from the National Institutes of Health 
and the State of Delaware. 

Acknowledgement 
The authors have no acknowledgements 

Conflicts of interest 
The authors report no conficlts of interest 

Authors' contributions 
Kindly add. S.M.: experimental procedures and 
contributed to the writing of the draft, L.F.: 
performed experimetnal procedures and 
manuscript reveiw., S.D.S.: conceptualiztion,  
manuscript review and editing, Z.S. 
conceptualization, manuscript review and editing, 
J.S.M.: conceptualization, statistical analysis, writing 
of the draft and review and editing of manuscript.   



 
 
 
 
 

 
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	Introduction
	Methods
	Patient samples and data
	Immunohistochemical procedure
	Statistical analysis

	Results
	Patient Characteristics
	Strong tumor ALDH1A1 staining is associated with race, stage, obesity, and diabetes.
	Strong tumor and stromal ALDH1A1 staining are associated with poor outcomes

	Discussion
	Financial support
	Acknowledgement
	Conflicts of interest
	Authors' contributions

