Effect of ALDH1 on prognosis and chemoresistance by breast cancer subtype

Abstract

Aldehyde dehydrogenase 1 (ALDH1) has been identified as a breast cancer stem cell marker, but its value as a predictor of prognosis and chemoresistance is controversial. This study investigated the effect of ALDH1 on prognosis and chemoresponse by breast cancer subtype. We immunohistochemically analyzed 653 invasive breast cancer specimens and evaluated correlations among clinicopathological factors, survival status, response to neoadjuvant chemotherapy, and ALDH1 expression. Of 653 specimens, 139 (21.3 %) expressed ALDH1 in tumor cells. ALDH1 expression was correlated significantly with larger tumor size, node metastasis, higher nuclear grade, and with HER2(+) and progesterone/estrogen receptor (HR)(-) subtypes. ALDH1 expression was significantly observed in HER2 type and triple-negative breast cancer (TNBC). Patients with ALDH1(+) cancers had significantly shorter disease-free survival (P < 0001) and overall survival (P = 0.044). ALDH1 expression significantly affected prognosis of luminal types, but not TNBC and HER2-enriched types. For the 234 patients treated with neoadjuvant chemotherapy, pathological complete response (pCR) rate was significantly lower in ALDH1(+) cases (13.5 vs. 30.3 %, P = 0.003). pCR and ALDH1 expression were significantly correlated in TNBC patients (P = 0.003). ALDH1(+) breast cancers tended to be aggressive, with poor prognoses. Although ALDH1(+) TNBC showed higher chemoresistance, ALDH1 had significant impact on prognosis in the luminal type but not in TNBC.

Evaluation of Breast Cancer Stem Cells and Intratumor Stemness Heterogeneity in Triple-negative Breast Cancer as Prognostic Factors

“…Here we did not find any association between ALDH1A1 expression and clinicopathologic features in TNBC. Although ALDH1 had a significant impact on prognosis in the other subtypes, it did not appear to correlate with the survival of TNBC patients 37-39. Here we showed a borderline significant trend of ALDH1A1+ phenotype for PFS.…”

Microenvironmental networks promote tumor heterogeneity and enrich for metastatic cancer stem-like cells in Luminal-A breast tumor cells

“…The ALDH1 enzyme is another stem cell marker which is particularly useful is studies of CSCs in culture, when contamination by other stem cells (such as hematopoietic stem cells) is not relevant [52, 53]. However, it was recently proposed that there are two distinct CSC sub-populations in breast cancer, one identified as CD44+/CD24 low/− and the other as ALDH1+ [54].…”

Aldehyde dehydrogenase 1 expression is correlated with poor prognosis in breast cancer

“…[12,27] CSC markers were reported to be present in CSCs as well as in normal stem cells, [9] with ALDH1 shown to be a marker of BCSCs. As BC is one of the most common tumors in women worldwide, so we conduct this study to explore the role of ALDH1 expression in BC.…”

“…[4–8] Many studies showed that ALDH1 is a marker of BCSCs, [3,5,9,10] while Kunju et al [11] reported that ALDH1-positive benign breast epithelial cells may predict an increased risk for the development of BC. Several studies suggested that ALDH1 is associated with an aggressive phenotype and poor prognosis, [12–16] although others found that it was not a survival predictor of BC [17–19] ; another study reported that expression of the major ALDH1 isoenzyme ALDH1A1 predicted a better outcome in BC of the triple-negative subtype. [20] The prognostic value of ALDH1 in BC is therefore controversial, and has not been fully elucidated.…”