title: Cytologic atypia in the contralateral unaffected breast is related to parity and estrogen-related genes.
abstract: OBJECTIVE
  The contralateral unaffected breast (CUB) of women with unilateral breast cancer provides a model for the study of breast tissue-based risk factors. Using random fine needle aspiration (rFNA), we have investigated hormonal and gene expression patterns related to atypia in the CUBs of newly diagnosed breast cancer patients.
  
  
  METHODS
  83 women underwent rFNA of the CUB. Cytologic analysis was performed using the Masood Score (MS), atypia was defined as MS > 14. RNA was extracted using 80% of the sample. The expression of 20 hormone related genes was quantified using Taqman Low Density Arrays. Statistical analysis was performed using 2-tailed t tests and linear regression.
  
  
  RESULTS
  Cytological atypia was more frequent in multiparous women (P = 0.0392), and was not associated with any tumor-related features in the affected breast. Masood Score was higher with shorter interval since last pregnancy (R = 0.204, P = 0.0417), higher number of births (R = 0.369, P = 0.0006), and estrogen receptor (ER) negativity of the index cancer (R = -0.203, P = 0.065). Individual cytologic features were associated with aspects of parity. Specifically, anisonucleosis was correlated with shorter interval since last pregnancy (R = 0.318, P = 0.0201), higher number of births (R = 0.382, P = 0.0004), and ER status (R = -0.314, P = 0.0038). Eight estrogen-regulated genes were increased in atypical samples (P < 0.005), including TFF1, AGT, PDZK1, PGR, GREB1, PRLR, CAMK2B, and CCND1.
  
  
  CONCLUSIONS
  Cytologic atypia, and particularly anisonucleosis, is associated with recent and multiple births and ER negative status of the index tumor. Atypical samples showed increased expression of estrogen-related genes, consistent with the role of estrogen exposure in breast cancer development.
authors: John H. Stroger Hospital of Cook County, Rush University Medical Center, Chicago, IL, USA.
authors: Denise A
authors: DA
authors: Monahan
authors: Department of Surgery, USA.
authors: Jun
authors: J
authors: Wang
authors: Department of Surgery, USA.
authors: Oukseub
authors: O
authors: Lee
authors: Jean McLaughlin Women's Center for Health, Healing and Comprehensive Breast Services, Poway CA, USA.
authors: Elizabeth
authors: E
authors: Revesz
authors: Little Company of Mary Hospital, Evergreen Park, IL, USA.
authors: Nancy
authors: N
authors: Taft
authors: Department of Surgery, USA.
authors: David
authors: D
authors: Ivancic
authors: Department of Surgery, USA; Lynn Sage Breast Center, USA.
authors: Nora M
authors: NM
authors: Hansen
authors: Department of Surgery, USA; Lynn Sage Breast Center, USA.
authors: Kevin P
authors: KP
authors: Bethke
authors: Kendall Regional Medical Center, Miami, FL, USA.
authors: C
authors: C
authors: Zalles
authors: Department of Surgery, USA; Lynn Sage Breast Center, USA; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address: skhan@nmh.org.
authors: Seema A
authors: SA
authors: Khan
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D044963:Biopsy, Fine-Needle; D001940:Breast / Q000166:cytology* / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D018275:Carcinoma, Lobular / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D016022:Case-Control Studies; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D010298:Parity; D011247:Pregnancy; D011379:Prognosis; D011960:Receptors, Estrogen / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D004967:Estrogens; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone
keywords: Anisonucleosis; Breast cancer risk; Contralateral unaffected breast; Cytologic atypia; Gene expression; Random fine needle aspiration