title: alphaB-crystallin is a novel predictor of resistance to neoadjuvant chemotherapy in breast cancer.
abstract: OBJECTIVE
  alphaB-crystallin is an anti-apoptotic protein commonly expressed in poor prognosis basal-like breast tumors, which are largely triple (estrogen receptor (ER), progesterone receptor (PR), and HER2) negative. We examined whether alphaB-crystallin expression in breast cancer was associated with a poor response to neoadjuvant (preoperative) chemotherapy.
  
  
  METHODS
  One hundred and twelve breast cancer patients who received neoadjuvant chemotherapy and who had post-chemotherapy tumor specimens available for analysis were included in the study. Forty-nine percent of patients were treated with doxorubicin and cyclophosphamide (AC), 37% received AC in combination with a taxane, and 14% received other regimens. Paired pre- and post-chemotherapy tumor specimens were available for 33 patients. alphaB-crystallin expression was determined by immunohistochemistry in tissue microarrays.
  
  
  RESULTS
  Seventeen percent of tumors were alphaB-crystallin positive. alphaB-crystallin expression was identical in 32 of 33 cases for which both pre- and post-chemotherapy tumor tissue was available. alphaB-crystallin expression was associated with ER-negative (P = 0.0024) and triple negative status (P = 0.005). Overall response rates (ORR) defined as > or =50% reduction in tumor size after treatment were 53% (clinical ORR) and 61% (pathological ORR). Although tumor grade, size, ER, PR, HER2 or triple negative status was not associated with response, alphaB-crystallin-positive tumors had poorer overall response rates than alphaB-crystallin-negative tumors (clinical ORR, 21% vs. 59%, respectively, P = 0.0045; pathological ORR, 16% vs. 70%, respectively, P < 0.0001).
  
  
  CONCLUSIONS
  alphaB-crystallin is a novel biomarker expressed predominantly in triple negative breast tumors that identifies a subset of chemotherapy-resistant tumors, which may contribute to their poor prognosis.
authors.affiliation: Department of Surgery, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Ivanov
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Wiley
authors.forename: Anjeni
authors.initials: A
authors.lastname: Keswani
authors.forename: Leslie K
authors.initials: LK
authors.lastname: Diaz
authors.forename: Heidi C
authors.initials: HC
authors.lastname: Memmel
authors.forename: Alfred
authors.initials: A
authors.lastname: Rademaker
authors.forename: William J
authors.initials: WJ
authors.lastname: Gradishar
authors.forename: Monica
authors.initials: M
authors.lastname: Morrow
authors.forename: Seema A
authors.initials: SA
authors.lastname: Khan
authors.forename: Vincent L
authors.initials: VL
authors.lastname: Cryns
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D017211:Treatment Failure; D038203:alpha-Crystallin B Chain / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D038203:alpha-Crystallin B Chain; C508053:ERBB2 protein, human