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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.

Miyoshi Y, Shien T, Ogiya A, Ishida N, Yamazaki K, Horii R, Horimoto Y, Masuda N, Yasojima H, Inao T, Osako T, Takahashi M, Tomioka N, Endo Y, Hosoda M, Doihara H, Miyoshi S, Yamashita H, Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Socie - Breast Cancer Res. (2016)

Bottom Line: We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups.Among 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.

View Article: PubMed Central - PubMed

Affiliation: Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama-city, Okayama, 700-8558, Japan.

ABSTRACT

Background: The 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.

Methods: In 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.

Results: The 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).

Conclusions: Among 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.

No MeSH data available.


Related in: MedlinePlus

Survival time from recurrence detection until death due to breast cancer. ALDH1 aldehyde dehydrogenase 1. a all cases with recurrence. b early recurrence cases. c late recurrence cases
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Fig2: Survival time from recurrence detection until death due to breast cancer. ALDH1 aldehyde dehydrogenase 1. a all cases with recurrence. b early recurrence cases. c late recurrence cases

Mentions: We analyzed 318 cases (early recurrence n = 184 [58 %], late recurrence 134 [42 %]) to compare overall survival from the time of recurrence detection between ALDH1-positive and ALDH1-negative cases (Fig. 2). The median follow-up duration from the detection of recurrence until death due to breast cancer was 39 (0–141) months in the early recurrence group and 34 (0–89) months in the late recurrence group. The Kaplan-Meier method showed a significant difference between ALDH1-positive and ALDH1-negative cases (p = 0.019). Moreover, the Kaplan-Meier method revealed a trend for higher ALDH1 expression in the early recurrence group (p = 0.082), while there was no difference in the late recurrence group (p = 0.27). Univariate analysis of all cases with recurrence revealed ALDH1 expression, nodal metastasis, and tumor grade to be significant prognostic factors. We selected significant parameters (p < 0.20) from among various conventional confounding factors and performed a multivariate analysis in which nodal metastasis, PgR, tumor grade, and Ki-67 expression served as categorical variables. In this multivariate analysis, lymph node metastasis (p = 0.036) and tumor grade (p = 0.038) were found to be independent prognostic factors, while ALDH1 expression was not (p = 0.059) (Table 7).Fig. 2


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.

Miyoshi Y, Shien T, Ogiya A, Ishida N, Yamazaki K, Horii R, Horimoto Y, Masuda N, Yasojima H, Inao T, Osako T, Takahashi M, Tomioka N, Endo Y, Hosoda M, Doihara H, Miyoshi S, Yamashita H, Collaborative Study Group of Scientific Research of the Japanese Breast Cancer Socie - Breast Cancer Res. (2016)

Survival time from recurrence detection until death due to breast cancer. ALDH1 aldehyde dehydrogenase 1. a all cases with recurrence. b early recurrence cases. c late recurrence cases
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4930566&req=5

Fig2: Survival time from recurrence detection until death due to breast cancer. ALDH1 aldehyde dehydrogenase 1. a all cases with recurrence. b early recurrence cases. c late recurrence cases
Mentions: We analyzed 318 cases (early recurrence n = 184 [58 %], late recurrence 134 [42 %]) to compare overall survival from the time of recurrence detection between ALDH1-positive and ALDH1-negative cases (Fig. 2). The median follow-up duration from the detection of recurrence until death due to breast cancer was 39 (0–141) months in the early recurrence group and 34 (0–89) months in the late recurrence group. The Kaplan-Meier method showed a significant difference between ALDH1-positive and ALDH1-negative cases (p = 0.019). Moreover, the Kaplan-Meier method revealed a trend for higher ALDH1 expression in the early recurrence group (p = 0.082), while there was no difference in the late recurrence group (p = 0.27). Univariate analysis of all cases with recurrence revealed ALDH1 expression, nodal metastasis, and tumor grade to be significant prognostic factors. We selected significant parameters (p < 0.20) from among various conventional confounding factors and performed a multivariate analysis in which nodal metastasis, PgR, tumor grade, and Ki-67 expression served as categorical variables. In this multivariate analysis, lymph node metastasis (p = 0.036) and tumor grade (p = 0.038) were found to be independent prognostic factors, while ALDH1 expression was not (p = 0.059) (Table 7).Fig. 2

Bottom Line: We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups.Among 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.

View Article: PubMed Central - PubMed

Affiliation: Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama-city, Okayama, 700-8558, Japan.

ABSTRACT

Background: The 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.

Methods: In 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.

Results: The 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).

Conclusions: Among 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.

No MeSH data available.


Related in: MedlinePlus