title: Immunohistochemical detection of breast cancer stem cells in hormone receptor-positive breast cancer and their role in response to endocrine therapy and clinical outcome.
abstract: BACKGROUND
  Breast cancer stem cells are rich in triple negative or human epidermal growth factor receptor-2-positive breast cancers. The role of these stem cells in hormone receptor-positive breast cancers is unknown. Therefore, we launched this retrospective biomarker analysis to clarify the role of stem cells in relation with endocrine therapy in hormone receptor-positive breast cancer.
  
  
  METHODS
  Formalin-fixed paraffin-embedded tissue samples from primary stage IV, hormone receptor-positive breast cancers prior to endocrine therapy were obtained from 4 cancer centers in Japan between 1999 and 2008. We examined the expression of ALDH1 and CD44/CD24 in breast tissue and correlated the results with response to endocrine therapy and patient prognosis.
  
  
  RESULTS
  ALDH1-positive and CD44+ CD24- cancer cells were found in 16% of 92 samples and 27% of 77 samples, respectively. Response to endocrine therapy was similar in the ALDH1-positive and ALDH1-negative tumor groups, and between CD44+ CD24- and other tumor groups. After a median follow-up period of 793 days, neither ALDH1 positivity nor CD44+ CD24- status of tumor cells was related to progression-free survival (ALDH1 positive vs. negative, 378 vs. 292 days, p = 0.53; CD44+ CD24- vs. others, 224 vs. 269 days, p = 0.52) or overall survival (ALDH1 positive vs. negative, 1,348 vs. 1,479 days, p = 0.17; CD44+ CD24- vs. others, 1,071 vs. 1,462 days, p = 0.54).
  
  
  CONCLUSIONS
  There is no correlation between biomarker expression and outcome in hormone receptor-positive breast cancer.
authors.affiliation: Department of Breast Oncology and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Chikako
authors.initials: C
authors.lastname: Shimizu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Shigehira
authors.initials: S
authors.lastname: Saji
authors.forename: Akihiko
authors.initials: A
authors.lastname: Osaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Shigekawa
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Aogi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000080924:Aldehyde Dehydrogenase 1 Family; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D051927:CD24 Antigen / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism; D007564:Japan; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000556:secondary; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D000080924:Aldehyde Dehydrogenase 1 Family; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D050697:Retinal Dehydrogenase; C497889:CD24 protein, human; C497483:CD44 protein, human; C510223:ALDH1A1 protein, human