title: Nipple aspiration and ductal lavage in women with a germline BRCA1 or BRCA2 mutation.
abstract: BACKGROUND
  The aim of this study was to collect serial samples of nipple aspirate (NA) and ductal lavage (DL) fluid from women with germline BRCA1/2 mutations in order to create a biorepository for use in identifying biomarkers of breast cancer risk.
  
  
  METHODS
  Between March 2003 and February 2005, 52 women with germline BRCA1 or BRCA2 mutations (median age 43 years, range 27 to 65 years) were scheduled for six-monthly NA, DL and venesection. DL was attempted for all NA fluid-yielding (FY) and any non-FY ducts that could be located at each visit.
  
  
  RESULTS
  Twenty-seven (52%) women were postmenopausal, predominantly (19/27) from risk reducing bilateral salpingo-oophorectomy (BSO). FY ducts were identified in 60% of all women, 76% of premenopausal women versus 44% of postmenopausal (P = 0.026). Eighty-five percent of women had successful DL. Success was most likely in women with FY ducts (FY 94% versus non-FY 71% (P = 0.049). DL samples were more likely to be cellular if collected from FY ducts (FY 68% versus non-FY 43%; P = 0.037). Total cell counts were associated with FY status (FY median cell count 30,996, range 0 to >1,000,000 versus non-FY median cell count 0, range 0 to 173,577; P = 0.002). Four women (8%) had ducts with severe atypia with or without additional ducts with mild epithelial atypia; seven others had ducts with mild atypia alone (11/52 (21%) in total). Median total cell count was greater from ducts with atypia (105,870, range 1920 to >1,000,000) than those with no atypia (174, 0 to >1,000,000; P <or= 0.001).
  
  
  CONCLUSIONS
  It is feasible to collect serial NA and DL samples from women at high genetic risk of breast cancer, and we are creating a unique, prospective collection of ductal samples that have the potential to be used for discovery of biomarkers of breast cancer risk and evaluate the ongoing effects of risk reducing BSO. DL cellular atypia was not predictive of a current breast cancer and longer follow up is needed to determine whether atypia is an additional marker of future breast cancer risk in this population already at high genetic risk of breast cancer.
authors.affiliation: Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia. gillian.mitchell@petermac.org
authors.forename: Gillian
authors.initials: G
authors.lastname: Mitchell
authors.forename: Yoland C
authors.initials: YC
authors.lastname: Antill
authors.forename: William
authors.initials: W
authors.lastname: Murray
authors.forename: Judy
authors.initials: J
authors.lastname: Kirk
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Salisbury
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Lindeman
authors.forename: Juliana
authors.initials: J
authors.lastname: Di Iulio
authors.forename: Alvin D
authors.initials: AD
authors.lastname: Milner
authors.forename: Lisa
authors.initials: L
authors.lastname: Devereaux
authors.forename: Kelly-Anne
authors.initials: KA
authors.lastname: Phillips
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D001826:Body Fluids / Q000737:chemistry / Q000166:cytology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D042361:Mammary Glands, Human / Q000737:chemistry / Q000166:cytology; D008875:Middle Aged; D009558:Nipples; D013048:Specimen Handling; D007507:Therapeutic Irrigation; D014015:Tissue Banks
chemical_list: D014408:Biomarkers, Tumor