Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2-negative breast cancer cases with early, late, and no recurrence

Abstract

BackgroundThe significance of the expression of aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, for predicting the recurrence of estrogen receptor (ER)-positive/human epidermal growth factor receptor type 2 (HER2)-negative breast cancer is still poorly understood. The value of ALDH1 in predicting the time of recurrence remains unknown.MethodsIn total, 184 patients with early distant recurrence, 134 patients with late distant recurrence, and 321 control patients without recurrence for more than 10 years after starting initial treatment for ER-positive/HER2-negative breast cancer, registered in 9 institutions, were analyzed. We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups. The relationship between ALDH1 expression and overall survival after recurrence was also evaluated in each group.ResultsThe rates of ALDH1 expression positivity (more than 1 %) in the early, late, and no recurrence groups were 18.4 %, 13.4 %, and 8.4 %, respectively. ALDH1 expression correlated significantly with lymph node metastases (p = 0.048) and the Ki-67 labeling index (p < 0.001) in the early recurrence group. Multivariate analysis revealed ALDH1 expression to be significantly higher in the early recurrence group than in the no recurrence group (adjusted OR 2.140, 95 % CI 1.144–4.003, p = 0.016). Moreover, there was a significant difference in ALDH1 expression between the early and no recurrence groups receiving adjuvant endocrine therapy and chemotherapy (adjusted OR 4.625, 95 % CI 1.881–12.474, p < 0.001). However, there was no difference in ALDH1 expression between the late and no recurrence groups in univariate analysis (OR 1.507, 95 % CI 0.738–2.998, p = 0.253). In multivariate analysis, ALDH1 was not a factor independently predicting overall survival after the detection of recurrence (adjusted OR 1.451, 95 % CI 0.985–2.085, p = 0.059).ConclusionsAmong patients with ER-positive/HER2-negative breast cancer, ALDH1 expression was more common in those with early recurrence, and this expression was found to be associated with a more aggressive breast cancer phenotype than that in the patients without recurrence. Further study is needed to clarify the prognostic significance of the heterogeneity of cancer stem cells and to confirm their role in resistance to chemotherapy.

LSD1 activation promotes inducible EMT programs and modulates the tumour microenvironment in breast cancer

“…CSV, ALDH1A and ABCB5 are all key markers of metastatic breast cancer (MBC) circulating tumour cells (CTCs). CTCs expressing CSV have been linked with poor prognosis in a variety of cancers 53 , 54 whilst ALDH1A expression is linked with metastasis in solid tumours and early recurrence 55 , 56 . Similarly, ABCB5 has been linked with poor prognosis and multi-drug resistance 57 , 58 .…”

Differential Functional Roles of ALDH1A1 and ALDH1A3 in Mediating Metastatic Behavior and Therapy Resistance of Human Breast Cancer Cells

“…High ALDH1 expression has been shown to correlate with poor prognosis in breast cancer patients [ 20 ], and has been associated with early relapse, metastasis development, therapy resistance and poor clinical outcome [ 7 , 8 , 21 , 22 , 23 ]. The ALDH1A1 isozyme has been shown to have increased expression in breast cancer patients who present with positive lymph nodes and in patients who succumb to their disease [ 24 ].…”

Prognostic value of aldehyde dehydrogenase 1 (ALDH1) in invasive breast carcinomas

“…Some authors reported a significant correlation between ALDH1 expression and axillary lymph node metastasis in BC [7,10]. Moreover, in a study that included only ER+/ HER2-breast carcinomas, ALDH1 expression was significantly associated with LNM in the group of patients with early recurrences [19]. Due to the small number of ALDH1+ cases in our study, we only compared ALDH1 expression between positive and negative lymph node status, and did not observe significant difference between the two groups.…”

“…Moreover, they reported that ALDH1 expression significantly affected the prognosis of luminal types, but not that of TNBC and HER2 type [10]. In the study which included only ER+/HER2-BC types, ALDH1 expression was significantly higher in the early recurrence group compared to the group without recurrence [19]. We compared the ratios of ALDH1 expression in each molecular subtype of BC and observed that ALDH1 expression was higher in HER2 type and TNBC (37.5% and 40.0%, respectively) compared to luminal A and luminal B types (10.6% and 31.8%, respectively).…”