title: 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.
authors.affiliation: Department of Gastroenterological Surgery and Surgical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Kida
authors.affiliation: Department of Breast Surgery, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo, Japan. tishik55@gmail.com.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Akimitsu
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Department of Gastroenterological Surgery and Surgical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shimada
authors.affiliation: Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Narui
authors.affiliation: Department of Gastroenterological Surgery and Surgical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Sadatoshi
authors.initials: S
authors.lastname: Sugae
authors.affiliation: Department of Gastroenterological Surgery and Surgical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shimizu
authors.affiliation: Department of Pathology, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Tanabe
authors.affiliation: Department of Pathology, Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Department of Gastroenterological Surgery and Surgical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ichikawa
authors.affiliation: Department of Gastroenterological Surgery and Surgical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000080924:Aldehyde Dehydrogenase 1 Family; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D016019:Survival Analysis; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*
chemical_list: D007527:Isoenzymes; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: ALDH1; Breast cancer; Chemoresistance; Prognosis; Stem cell; Subtype