title: 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: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.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.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Miyoshi
authors.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. tshien@md.okayama-u.ac.jp.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Shien
authors.affiliation: Breast Surgical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ogiya
authors.affiliation: Breast Surgery, Hokkaido University Hospital, Kita-14, Nishi-5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ishida
authors.affiliation: Breast Surgical Oncology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
authors.forename: Kieko
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Division of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Horii
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Horimoto
authors.affiliation: Breast Oncology, Department of Surgery, National Hospital Organization (NHO) Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka, Osaka, 540-0006, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Masuda
authors.affiliation: Breast Oncology, Department of Surgery, National Hospital Organization (NHO) Osaka National Hospital, 2-1-14 Hoenzaka, Chuo-ku, Osaka, Osaka, 540-0006, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasojima
authors.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, Kumamoto, 860-8556, Japan.
authors.forename: Touko
authors.initials: T
authors.lastname: Inao
authors.affiliation: Department of Breast and Endocrine Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Higashi-ku, Kumamoto, Kumamoto, 862-8505, Japan.|Present address: Kumamoto Shinto General Hospital, 1-17-27 Shinyashiki, Chuo-ku, Kumamoto, Kumamoto, 862-8655, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Osako
authors.affiliation: Department of Breast Surgery, National Hospital Organization (NHO) Hokkaido Cancer Center, 4-2-3-54 Kikusui, Shiroishi-ku, Sapporo, Hokkaido, 003-0804, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Breast Surgery, National Hospital Organization (NHO) Hokkaido Cancer Center, 4-2-3-54 Kikusui, Shiroishi-ku, Sapporo, Hokkaido, 003-0804, Japan.
authors.forename: Nobumoto
authors.initials: N
authors.lastname: Tomioka
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Breast Surgery, Hokkaido University Hospital, Kita-14, Nishi-5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.
authors.forename: Mitsuchika
authors.initials: M
authors.lastname: Hosoda
authors.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.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Doihara
authors.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.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Miyoshi
authors.affiliation: Breast Surgery, Hokkaido University Hospital, Kita-14, Nishi-5, Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamashita
mesh_terms: D000328:Adult; D000368:Aged; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D050697:Retinal Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D050697:Retinal Dehydrogenase; C510223:ALDH1A1 protein, human
keywords: Aldehyde dehydrogenase 1; Breast cancer; Estrogen receptor-positive; Human epidermal growth factor receptor type 2-negative; Time of recurrence