title: The effects of soy supplementation on gene expression in breast cancer: a randomized placebo-controlled study.
abstract: BACKGROUND
  There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways.
  
  
  METHODS
  Women (n = 140) with early-stage breast cancer were randomly assigned to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString in pre- and posttreatment tumor tissue. Genome-wide expression analysis was performed on posttreatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry.
  
  
  RESULTS
  Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and posttreatment samples, 21 genes (out of 202) showed altered expression (two-sided Student's t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student's t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2-fold) of cell cycle transcripts, including those that promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3.
  
  
  CONCLUSIONS
  Gene expression associated with soy intake and high plasma genistein defines a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer.
authors.affiliation: Department of Medicine (MS, AD, LR, JB, LN) and Department of Pathology (RC, JRF, WG) and Department of Surgery (HC) and Department of Computational Biology (RK), Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College (MS, JRF, WG, HC, JB, LN). shikem@mskcc.org.
authors.forename: Moshe
authors.initials: M
authors.lastname: Shike
authors.affiliation: Department of Medicine (MS, AD, LR, JB, LN) and Department of Pathology (RC, JRF, WG) and Department of Surgery (HC) and Department of Computational Biology (RK), Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College (MS, JRF, WG, HC, JB, LN).
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Doane
authors.affiliation: Department of Medicine (MS, AD, LR, JB, LN) and Department of Pathology (RC, JRF, WG) and Department of Surgery (HC) and Department of Computational Biology (RK), Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College (MS, JRF, WG, HC, JB, LN).
authors.forename: Lianne
authors.initials: L
authors.lastname: Russo
authors.affiliation: Department of Medicine (MS, AD, LR, JB, LN) and Department of Pathology (RC, JRF, WG) and Department of Surgery (HC) and Department of Computational Biology (RK), Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College (MS, JRF, WG, HC, JB, LN).
authors.forename: Rafael
authors.initials: R
authors.lastname: Cabal
authors.affiliation: Department of Medicine (MS, AD, LR, JB, LN) and Department of Pathology (RC, JRF, WG) and Department of Surgery (HC) and Department of Computational Biology (RK), Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College (MS, JRF, WG, HC, JB, LN).
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.affiliation: Department of Medicine (MS, AD, LR, JB, LN) and Department of Pathology (RC, JRF, WG) and Department of Surgery (HC) and Department of Computational Biology (RK), Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College (MS, JRF, WG, HC, JB, LN).
authors.forename: William
authors.initials: W
authors.lastname: Gerald
authors.affiliation: Department of Medicine (MS, AD, LR, JB, LN) and Department of Pathology (RC, JRF, WG) and Department of Surgery (HC) and Department of Computational Biology (RK), Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College (MS, JRF, WG, HC, JB, LN).
authors.forename: Hiram
authors.initials: H
authors.lastname: Cody
authors.affiliation: Department of Medicine (MS, AD, LR, JB, LN) and Department of Pathology (RC, JRF, WG) and Department of Surgery (HC) and Department of Computational Biology (RK), Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College (MS, JRF, WG, HC, JB, LN).
authors.forename: Raya
authors.initials: R
authors.lastname: Khanin
authors.affiliation: Department of Medicine (MS, AD, LR, JB, LN) and Department of Pathology (RC, JRF, WG) and Department of Surgery (HC) and Department of Computational Biology (RK), Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College (MS, JRF, WG, HC, JB, LN).
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Bromberg
authors.affiliation: Department of Medicine (MS, AD, LR, JB, LN) and Department of Pathology (RC, JRF, WG) and Department of Surgery (HC) and Department of Computational Biology (RK), Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College (MS, JRF, WG, HC, JB, LN).
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements / Q000009:adverse effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019833:Genistein / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry; D007529:Isoflavones / Q000097:blood; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*; D030262:Soybean Proteins / Q000008:administration & dosage* / Q000009:adverse effects*; D046888:Tissue Array Analysis; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D007529:Isoflavones; D019394:Ki-67 Antigen; D030262:Soybean Proteins; C004742:daidzein; D019833:Genistein; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D053148:Caspase 3