title: Association of HER-2 copy number and HER-2/CEP-17 ratio with neoadjuvant taxane-containing chemotherapy sensitivity in locally advanced breast cancer.
abstract: OBJECTIVE
  Aneusomy 17 causes inconsistency in fluorescence in situ hybridization (FISH)-based human epidermal growth factor receptor (HER)-2 status assessment using different algorithms (copy number or the HER-2/centromere enumerator probe 17 [CEP-17] ratio). We investigated the effects of FISH-based HER-2 status assessment and aneusomy 17 on responsiveness to neoadjuvant chemotherapy (NAC).
  
  
  METHODS
  This prospective study recruited 152 patients with locally advanced breast cancer who underwent four-cycle weekly paclitaxel plus carboplatin without trastuzumab.
  
  
  RESULTS
  The pathologic complete remission (pCR) rate in the breast and axilla was 24.3% (95% confidence interval [CI], 17.7%-32.0%). Although HER-2 status, assessed by either HER-2/CEP-17 ratio-based FISH or copy number-based FISH, was a predictor of NAC sensitivity, ratio-assessed HER-2 status had a poorer performance in determining patients' responsiveness to NAC (p = .029). Patients who were not HER-2 amplified when assessed using the HER-2/CEP-17 ratio but were HER-2 amplified when assessed using copy number (~5%) were eventually proven to be responsive to NAC, with a pCR rate of 57% (95% CI, 18.4%-90.1%). In contrast, patients who were HER-2 amplified when assessed by the ratio but not HER-2 amplified when assessed using copy number (~3%) were completely irresponsive. Higher HER-2 copy numbers represented increasing chances of a pCR (adjusted odds ratio, 3.09; 95% CI, 1.35-7.08), with an apparent gene-dose effect (p for trend < .001).
  
  
  CONCLUSIONS
  It is likely that HER-2 copy number but not the HER-2/CEP-17 ratio determines NAC sensitivity. Additional studies to validate our findings are warranted.
authors.affiliation: Department of Breast Surgery, Cancer Center and Cancer Institute, Fudan University, 399 Ling-Ling Road, Shanghai, P.R. China.
authors.forename: Ke-Da
authors.initials: KD
authors.lastname: Yu
authors.forename: Guang-Yu
authors.initials: GY
authors.lastname: Liu
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jiong
authors.initials: J
authors.lastname: Wu
authors.forename: Can-Ming
authors.initials: CM
authors.lastname: Chen
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Shen
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001365:Axilla / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D002886:Chromosomes, Human, Pair 17; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016015:Logistic Models; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000627:therapeutic use; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D043823:Taxoids / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D016190:Carboplatin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C080625:taxane; C508053:ERBB2 protein, human