title: Prognostic value of circulating tumor cells according to immunohistochemically defined molecular subtypes in advanced breast cancer.
abstract: BACKGROUND
  Breast cancer is a heterogeneous disease. Circulating tumor cell (CTC) enumeration might be useful to identify different risk categories within each molecular subtype.
  
  
  METHODS
  We retrospectively analyzed 203 consecutive patients with metastatic breast cancer with baseline CTC enumeration performed with CellSearch (Veridex Corp, Warren, NJ) between March 2005 and July 2011. Patients were categorized into 3 prognostic groups based on the number of CTCs (0, 1-4, and ≥ 5) and into 5 categories based on tumor biological characteristics: luminal-A (estrogen receptor [ER] and progesterone receptor [PR] > 1%, grade 1/2, human epidermal growth factor 2 [HER2]-negative [HER2(-)], Ki67 value < 14%); luminal-B (ER and/or PR > 1%, grade 3, HER2(-), Ki67 value > 14%); luminal-B HER2-positive [HER2(+)] (ER and/or PR > 1%, any grade, HER2(+), Ki-67 value any); HER2(+) (HER2 overexpressed/fluorescence in situ hybridization [FISH] amplified, ER and PR absent); triple negative (TN) (ER and PR 0%, HER2 not overexpressed/FISH not amplified).
  
  
  RESULTS
  Median age was 57 years (range 31-78 years). Twenty-seven patients (13.3%) had luminal-A category, 105 (51.7%) patients had luminal-B, 29 (14.3%) patients had luminal-B HER2(+), 24 patients (11.8%) had HER2(+), and 18 patients (8.9%) had TN. CTCs were mostly found in patients with luminal-A/luminal-B HER2(-) subtype. At multivariable analysis, CTC count was a significant predictive factor for overall survival (OS) in all molecular subtypes (log-rank P < .01). Patients with 0 CTCs/7.5 mL blood and all subtypes, except HER2(+), seem to perform better compared with other categories.
  
  
  CONCLUSIONS
  These findings confirm CTCs as an important prognostic factor for metastatic breast cancer in all molecular subtypes. Larger studies could help identify metastatic breast cancer subgroups in which CTC analysis would be particularly useful.
authors.affiliation: Division of Medical Oncology, Istituto Europeo di Oncologia, Milan, Italy. elisabetta.munzone@ieo.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Munzone
authors.forename: Edoardo
authors.initials: E
authors.lastname: Botteri
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Sandri
authors.forename: Angela
authors.initials: A
authors.lastname: Esposito
authors.forename: Laura
authors.initials: L
authors.lastname: Adamoli
authors.forename: Laura
authors.initials: L
authors.lastname: Zorzino
authors.forename: Angela
authors.initials: A
authors.lastname: Sciandivasci
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Cassatella
authors.forename: Nicole
authors.initials: N
authors.lastname: Rotmensz
authors.forename: Gaetano
authors.initials: G
authors.lastname: Aurilio
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Curigliano
authors.forename: Aron
authors.initials: A
authors.lastname: Goldhirsch
authors.forename: Franco
authors.initials: F
authors.lastname: Nolè
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone