title: Relative Prognostic and Predictive Value of Gene Signature and Histologic Grade in Estrogen Receptor-Positive, HER2-Negative Breast Cancer.
abstract: BACKGROUND
  In estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, first-generation genomic signatures serve predominately as prognostic biomarkers and secondarily as predictors of response to chemotherapy. We compared both the prognostic and predictive value of histologic grades and genomic markers.
  
  
  METHODS
  We retrieved publicly available cDNA microarray data from 1373 primary ER(+)/HER2(-) breast cancers and developed a genomic signature simulated from Recurrence Online (http://www.recurrenceonline.com/) to calculate the recurrence score and risk using predefined sets of genes in the cDNA microarray. We then compared the prognostic and predictive information provided by histologic grade and genomic signature.
  
  
  RESULTS
  Based on genomic signatures, 55%, 28%, and 17% of breast cancers were classified as low, intermediate, and high risk, respectively, whereas the histologic grades were I, II, and III in 22%, 59%, and 19% of breast cancers, respectively. Univariate analysis in the untreated cohort revealed that both histologic grade (overall P = .007) and genomic signature (P < .001) could predict prognosis. Results were similar using the genomic signature, with pathologic complete response rates of 4.6%, 5.7%, and 16.5% for low-, intermediate-, and high-risk cancers, respectively. Neither biomarker was statistically significant in multivariate analysis for predictive response to neoadjuvant chemotherapy (NAC).
  
  
  CONCLUSIONS
  Genomic signature was better at identifying low-risk cases compared to histologic grade alone, but both markers had similar predictive values for NAC response. Better predictive biomarkers for NAC response are still needed.
authors.affiliation: Okayama University Hospital, Okayama, Japan. Electronic address: tiwamoto@cc.okayama-u.ac.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Iwamoto
authors.affiliation: Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Catherine
authors.initials: C
authors.lastname: Kelly
authors.affiliation: Okayama University Hospital, Okayama, Japan.
authors.forename: Taeko
authors.initials: T
authors.lastname: Mizoo
authors.affiliation: Okayama University Hospital, Okayama, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nogami
authors.affiliation: Okayama University Hospital, Okayama, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Motoki
authors.affiliation: Okayama University Hospital, Okayama, Japan.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Shien
authors.affiliation: Okayama University Hospital, Okayama, Japan.
authors.forename: Naruto
authors.initials: N
authors.lastname: Taira
authors.affiliation: Department of Breast Surgery, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayashi
authors.affiliation: Department of Breast and Endocrine Surgery, Tokai University Hospital, Kanagawa, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Niikura
authors.affiliation: Okayama University Hospital, Okayama, Japan.
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Okayama University Hospital, Okayama, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Doihara
authors.affiliation: Okayama University Hospital, Okayama, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Matsuoka
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Breast cancer; Chemotherapy response; Genomic marker; Grade; Predictive marker