25190728
BACKGROUND	There are conflicting reports on the impact of soy on breast carcinogenesis .
BACKGROUND	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 .
METHODS	Adherence was determined by plasma isoflavones : genistein and daidzein .
METHODS	Gene expression changes were evaluated by NanoString in pre - and posttreatment tumor tissue .
METHODS	Genome-wide expression analysis was performed on posttreatment tissue .
METHODS	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 .
RESULTS	In paired analysis of pre - and posttreatment samples , 21 genes ( out of 202 ) showed altered expression ( two-sided Student 's t-test , P < .05 ) .
RESULTS	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 ) .
RESULTS	A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors .
RESULTS	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 ) .
RESULTS	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 .
CONCLUSIONS	These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer .

