title: Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes fails to predict breast cancer recurrence: a final analysis of a prospective multi-institutional cohort study.
abstract: BACKGROUND
  To address the clinical relevance of molecular detection of occult breast cancer in sentinel lymph nodes and nonsentinel axillary lymph nodes (ALN), we initiated the Minimally Invasive Molecular Staging of Breast Cancer (MIMS) trial, a multi-institutional prospective cohort study. This trial represents the first prospective cohort study in which a multimarker, real-time reverse transcription polymerase chain reaction (RT-PCR) analysis was applied to the detection of breast cancer micrometastases in ALN.
  
  
  METHODS
  Sentinel and/or nonsentinel ALN from 501 breast cancer subjects with T1-T3 primary tumors were analyzed by standard histopathology and multimarker, real-time RT-PCR analysis. Seven breast cancer-associated genes (mam, mamB, PIP, CK19, muc1, PSE, and CEA) known to be overexpressed in metastatic breast cancer compared with control lymph nodes were used. Follow-up data were collected for 5 years.
  
  
  RESULTS
  Of the 501 breast cancer subjects enrolled, 348 were node negative and completed the 5-year follow-up. Of these patients (n = 94), 27% demonstrated evidence of molecular overexpression. The 5-year relapse-free survival rate was 95.4% (95% confidence interval [95% CI], 92.4-97.2%). No single gene or combination of study genes was predictive of recurrence.
  
  
  CONCLUSIONS
  The genes in this study panel failed to be predictive of clinical relapse. This may be a function of several factors: the low event rate at 5 years, the particular gene set, the methodology used for detection/analysis or that our original hypothesis was wrong and that the presence of positive marker signal by real-time RT-PCR is not associated with a worsened clinical outcome.
authors.affiliation: Department of Surgery, Medical University of South Carolina, Charleston, SC, USA. fisherca@wudosis.wustl.edu
authors.forename: Carla Suzanne
authors.initials: CS
authors.lastname: Fisher
authors.forename: David J
authors.initials: DJ
authors.lastname: Cole
authors.forename: Michael
authors.initials: M
authors.lastname: Mitas
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett-Meyer
authors.forename: John S
authors.initials: JS
authors.lastname: Metcalf
authors.forename: William E
authors.initials: WE
authors.lastname: Gillanders
authors.forename: Kaidi
authors.initials: K
authors.lastname: Mikhitarian
authors.forename: Marshall M
authors.initials: MM
authors.lastname: Urist
authors.forename: G Bruce
authors.initials: GB
authors.lastname: Mann
authors.forename: Gerard
authors.initials: G
authors.lastname: Doherty
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Herrmann
authors.forename: Arnold D
authors.initials: AD
authors.lastname: Hill
authors.forename: Oleg
authors.initials: O
authors.lastname: Eremin
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Sheemy
authors.forename: Richard K
authors.initials: RK
authors.lastname: Orr
authors.forename: Alvaro A
authors.initials: AA
authors.lastname: Valle
authors.forename: Michael A
authors.initials: MA
authors.lastname: Henderson
authors.forename: Robert L
authors.initials: RL
authors.lastname: Dewitty
authors.forename: Sonia L
authors.initials: SL
authors.lastname: Sugg
authors.forename: Eric
authors.initials: E
authors.lastname: Frykberg
authors.forename: Karen
authors.initials: K
authors.lastname: Yeh
authors.forename: Richard M
authors.initials: RM
authors.lastname: Bell
authors.forename: Megan K
authors.initials: MK
authors.lastname: Baker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001365:Axilla; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D044584:Carcinoma, Ductal / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D018275:Carcinoma, Lobular / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger