title: Low FOXA1 expression predicts good response to neo-adjuvant chemotherapy resulting in good outcomes for luminal HER2-negative breast cancer cases.
abstract: BACKGROUND
  FOXA1 expression is a good prognostic marker for endocrine therapy in hormone-positive breast cancer. We retrospectively examined breast cancer patients with luminal human epidermal growth factor receptor 2 (HER2)-negative tumours, as defined by immunohistochemistry, who received neo-adjuvant chemotherapy (NAC) and investigated the relationship between treatment effects and FOXA1 expression.
  
  
  METHODS
  Biopsy specimens from 103 luminal HER2-negative tumours were immunohistochemically examined. FOXA1 effects on chemo-sensitivity were also investigated employing in vitro experiments.
  
  
  RESULTS
  FOXA1 and Ki67 expressions independently predicted a pathological complete response (pCR). Knockdown of FOXA1 by siRNA boosted the chemo-effect in oestrogen receptor-positive cells. The Cox hazards model revealed a pCR to be the strongest factor predicting a good patient outcome.
  
  
  CONCLUSIONS
  Our present study showed low FOXA1 expression to be associated with a good response to NAC in luminal HER2-negative breast cancer. Improved outcomes of these patients suggest that NAC should be recommended to patients with low FOXA1 tumours.
authors.affiliation: 1] Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan [2] Department of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Horimoto
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Arakawa
authors.affiliation: Division of Cancer, Department of Surgery and Cancer, 1st Floor, ICTEM Building, Hammersmith Hospital, Imperial College London, London W12 0NN, UK.
authors.forename: N
authors.initials: N
authors.lastname: Harada-Shoji
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sonoue
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Himuro
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Igari
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Tokuda
authors.affiliation: Department of Human Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Mamat
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanabe
authors.affiliation: Department of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Hino
authors.affiliation: Department of Breast Oncology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Saito
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001952:Bridged-Ring Compounds; D003520:Cyclophosphamide; D000077143:Docetaxel; D015251:Epirubicin; D005472:Fluorouracil; D051541:Hepatocyte Nuclear Factor 3-alpha; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; D043823:Taxoids; C496499:FOXA1 protein, human; C080625:taxane; C508053:ERBB2 protein, human