title: High expression of class III β-tubulin predicts good response to neoadjuvant taxane and doxorubicin/cyclophosphamide-based chemotherapy in estrogen receptor-negative breast cancer.
abstract: BACKGROUND
  Expression of class ΙΙΙ β-tubulin (βΙΙΙ-tubulin) correlates with tumor progression and resistance to taxane-based therapies for several human malignancies including breast cancer. However its predictive value in a neoadjuvant setting in breast cancer remains unexplored. The objective of this explorative study was to determine whether βΙΙΙ-tubulin expression in breast cancer correlated with pathologic characteristics and whether its expression was predictive of response to neoadjuvant chemotherapy.
  
  
  METHODS
  We determined βΙΙΙ-tubulin expression in 85 breast cancers, including 41 localized breast cancers treated with primary surgery and 44 treated with neoadjuvant chemotherapy before surgery. βΙΙΙ-tubulin expression was evaluated by immunohistochemical methods and was correlated with pathologic characteristics and response to neoadjuvant chemotherapy using residual cancer burden (RCB) score.
  
  
  RESULTS
  High βΙΙΙ-tubulin expression was significantly associated with poorly differentiated high-grade breast cancers (P = .003) but not with tumor size, estrogen receptor (ER) status, or human epidermal growth factor receptor 2 (HER2)/neu overexpression. In ER(-) tumors treated with neoadjuvant chemotherapy, high βΙΙΙ-tubulin expression was associated with a significantly greater likelihood of achieving a good pathologic response to chemotherapy as reflected by lower RCB scores (P = .021).
  
  
  CONCLUSIONS
  This study reveals differential βΙΙΙ-tubulin expression in breast cancers of different histologic grades, hormone receptors, and HER2/neu status. It also suggests a potential role for βΙΙΙ-tubulin as a predictive biomarker for response in neoadjuvant chemotherapy for ER(-) breast cancer, which has not been previously reported. These data provide a strong rationale for considering βΙΙΙ-tubulin status and further validation of this marker in a large study.
authors.affiliation: Department of Pathology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA. yw232687@gmail.com
authors.forename: Yihong
authors.initials: Y
authors.lastname: Wang
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
authors.forename: Susan
authors.initials: S
authors.lastname: Fineberg
authors.forename: Lesley
authors.initials: L
authors.lastname: Stead
authors.forename: Jaya
authors.initials: J
authors.lastname: Sunkara
authors.forename: Susan Band
authors.initials: SB
authors.lastname: Horwitz
authors.forename: Hayley M
authors.initials: HM
authors.lastname: McDaid
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D012189:Retrospective Studies; D043823:Taxoids / Q000008:administration & dosage; D014404:Tubulin / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D003520:Cyclophosphamide; D004317:Doxorubicin; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D043823:Taxoids; D014404:Tubulin; C498585:TUBB3 protein, human; C080625:taxane