title: High HER2/Centromeric Probe for Chromosome 17 Fluorescence In Situ Hybridization Ratio Predicts Pathologic Complete Response and Survival Outcome in Patients Receiving Neoadjuvant Systemic Therapy With Trastuzumab for HER2-Overexpressing Locally Advanced Breast Cancer.
abstract: BACKGROUND
  The present study was performed to determine whether the human epidermal growth factor receptor-related 2 (HER2)/centromeric probe for chromosome 17 fluorescence in situ hybridization (FISH) ratio is a predictor of a pathologic complete response (pCR), recurrence-free survival (RFS), and/or overall survival (OS) in patients receiving neoadjuvant systemic treatment (NST) with trastuzumab (NST-T) for HER2+ locally advanced breast cancer (LABC).
  
  
  METHODS
  The present retrospective study included 555 patients with HER2+ LABC who had undergone NST and definitive surgery (1999-2012); 373 had concurrently received trastuzumab. HER2-positivity was considered present with an immunohistochemical score of 3+ and/or HER2 FISH ratio of ≥2.0. We used logistic regression analysis and Cox proportional hazard modeling to determine whether a high HER2 FISH ratio, either as a continuous variable or with a cutoff of ≥7.0, would predict for pCR (no invasive disease in the breast and no tumor in the ipsilateral axillary lymph nodes), RFS, and/or OS.
  
  
  RESULTS
  The pCR group's median HER2 FISH ratio was significantly higher than that of the non-pCR group (6.4 vs. 5.2; p = .003). The logistic regression model demonstrated that the independent predictors of pCR included a high HER2 FISH ratio as a continuous variable (p = .04). The multicovariate Cox proportional hazard model showed that a high HER2 FISH ratio (with a cutoff of ≥7.0 or as a continuous variable) was a significant prognostic indicator of longer RFS time (p = .047 and p = .04, respectively). Similarly, a high HER2 FISH ratio of ≥7.0 was associated with longer OS (p = .06).
  
  
  CONCLUSIONS
  A high HER2 FISH ratio is a predictor of pCR in patients with HER2+ LABC who receive NST-T.
  
  
  CONCLUSIONS
  This study demonstrated the optimal predictive and prognostic value of a HER2/centromeric probe for chromosome 17 FISH ratio for primary HER2+ breast cancer treated with trastuzumab combined with neoadjuvant systemic treatment (NST-T). This suggests that a high HER2 FISH ratio is a potential indicator for a high pathologic complete response rate and a better prognosis when patients are treated with NST-T.
authors.affiliation: Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kogawa
authors.affiliation: Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Tamer M
authors.initials: TM
authors.lastname: Fouad
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Diane D
authors.initials: DD
authors.lastname: Liu
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jimin
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Masuda
authors.affiliation: Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Takeo
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Chavez-MacGregor
authors.affiliation: Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Ricardo H
authors.initials: RH
authors.lastname: Alvarez
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobágyi
authors.affiliation: Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.affiliation: Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA nueno@mdanderson.org.
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002503:Centromere / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D012189:Retrospective Studies; D000068878:Trastuzumab / Q000008:administration & dosage
chemical_list: D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: HER2+ breast cancer; HER2/centromeric probe for chromosome 17 fluorescence in situ hybridization ratio; Pathologic complete response; Predictive factor; Trastuzumab